NCBI Conserved Domain Search

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270921 [Multi-domain] Cd Length: 252 Bit Score: 246.36 E-value: 2.97e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   1 MGVKYCFRKNDHVVIAMPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDF 80
Cdd:cd14019    67 SGLITAFRNEDQVVAVLPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDF 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  81 GLAQGTHDtkiellkfvqseaqqercsqnkshiitgnkiplsgpvpkeldqqsttkasvkrpytnaqiqikqgkdgkegs 160
Cdd:cd14019   147 GLAQREED------------------------------------------------------------------------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 161 vglsvqrsvfgernfnihssishespavklmkqsktvdvlsrklatkkkaistkvmnsavmrktasscpasltcdcyatd 240
Cdd:cd14019       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 kvcsiclsRRQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSRETI 320
Cdd:cd14019   155 --------RPEQRAPRAGTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFSSDDIDALAEIATIFGSDEAY 226


                  .
gi 1034562195 321 Q 321
Cdd:cd14019   227 D 227

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

Pssm-ID: 214567 [Multi-domain] Cd Length: 254 Bit Score: 87.59 E-value: 2.01e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195    3 VKYCFRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaL 77
Cdd:smart00220  62 LYDVFEDEDKLYLVMEYCEGGDLFDLLKKrgrLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDghVK---L 138

                           90
                   ....*....|..
gi 1034562195   78 VDFGLAQGTHDT 89
Cdd:smart00220 139 ADFGLARQLDPG 150

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

Pssm-ID: 270622 [Multi-domain] Cd Length: 215 Bit Score: 81.93 E-value: 7.29e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNS----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYA 76
Cdd:cd00180    54 VKLydVFETENFLYLVMEYCEGGSLKDLLKEnkgpLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDG-TVK 132


                  ....*..
gi 1034562195  77 LVDFGLA 83
Cdd:cd00180   133 LADFGLA 139

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270916 [Multi-domain] Cd Length: 260 Bit Score: 78.40 E-value: 2.76e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  10 NDHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQ 84
Cdd:cd14014    72 DGRPYIVMEYVEGGSLADLLRergPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEdgRVK---LTDFGIAR 148


                  ....*..
gi 1034562195  85 GTHDTKI 91
Cdd:cd14014   149 ALGDSGL 155

Serine/threonine protein kinase [Signal transduction mechanisms];

Pssm-ID: 440281 [Multi-domain] Cd Length: 482 Bit Score: 77.75 E-value: 2.88e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFG 81
Cdd:COG0515    76 GEEDGRPYLVMEYVEGESLADLLRRrgpLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPdgRVK---LIDFG 152


                  ..
gi 1034562195  82 LA 83
Cdd:COG0515   153 IA 154

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271034 [Multi-domain] Cd Length: 306 Bit Score: 74.89 E-value: 8.98e-15

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  17 MPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA 83
Cdd:cd14132    94 FEYVNNTDFKTLYPTLTDYDIRYYMYELLKALDYCHSKGIMHRDVKPHNIMIDHEKRKLRLIDWGLA 160

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270692 [Multi-domain] Cd Length: 254 Bit Score: 69.15 E-value: 3.95e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNSL--SFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKk 74
Cdd:cd05122    60 VKYygSYLKKDELWIVMEFCSGGSLKDLLKNTnkTLTEqqIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDgeVK- 138


                  ....*....
gi 1034562195  75 yaLVDFGLA 83
Cdd:cd05122   139 --LIDFGLS 145

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270688 [Multi-domain] Cd Length: 249 Bit Score: 68.80 E-value: 4.88e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLeHESFLDIL--NSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGL 82
Cdd:cd05118    70 HRGGNHLCLVFELM-GMNLYELIkdYPRGLPLdlIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQLKLADFGL 148


                  .
gi 1034562195  83 A 83
Cdd:cd05118   149 A 149

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270751 [Multi-domain] Cd Length: 386 Bit Score: 69.29 E-value: 9.89e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVD 79
Cdd:cd05600    78 YAFQDPENVYLAMEYVPGGDFRTLLNNsgiLSEEHARFYIAEMFAAISSLHQLGYIHRDLKPENFLIDSSghIK---LTD 154

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1034562195  80 FGLAQGT-HDTKIELLKF----VQSEAQQERCSQNKSHII 114
Cdd:cd05600   155 FGLASGTlSPKKIESMKIrleeVKNTAFLELTAKERRNIY 194

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173741 [Multi-domain] Cd Length: 293 Bit Score: 66.09 E-value: 6.73e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  11 DHVVIAMPYLEHE--SFLDILN-SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 83
Cdd:cd07843    79 DKIYMVMEYVEHDlkSLMETMKqPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRgiLK---ICDFGLA 153

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270731 [Multi-domain] Cd Length: 272 Bit Score: 64.16 E-value: 2.17e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEH---ESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVD 79
Cdd:cd05579    60 YSFQGKKNLYLVMEYLPGgdlYSLLENVGALDEDVARIYIAEIVLALEYLHSHGIIHRDLKPDNILIDAngHLK---LTD 136


                  ...
gi 1034562195  80 FGL 82
Cdd:cd05579   137 FGL 139

Protein kinase domain;

Pssm-ID: 459660 [Multi-domain] Cd Length: 217 Bit Score: 62.65 E-value: 3.84e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 256 RAGTPGFRAPEVLtKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSREtiqaaktfgKSILCSKE 335
Cdd:pfam00069 120 FVGTPWYMAPEVL-GGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPE---------LPSNLSEE 189

                          90
                  ....*....|...
gi 1034562195 336 vpAQDL-RKLCER 347
Cdd:pfam00069 190 --AKDLlKKLLKK 200

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270827 [Multi-domain] Cd Length: 288 Bit Score: 63.11 E-value: 5.38e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHeSFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDF 80
Cdd:cd07833    69 FRRKGRLYLVFEYVER-TLLELLeaspGGLPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESgvLK---LCDF 144


                  ...
gi 1034562195  81 GLA 83
Cdd:cd07833   145 GFA 147

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270733 [Multi-domain] Cd Length: 278 Bit Score: 63.00 E-value: 5.60e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLKkyaLVD 79
Cdd:cd05581    68 YTFQDESKLYFVLEYAPNGDLLEYIRkygSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILldEDMHIK---ITD 144

                          90       100
                  ....*....|....*....|....*
gi 1034562195  80 FGLAQGTHDTKIELLKFVQSEAQQE 104
Cdd:cd05581   145 FGTAKVLGPDSSPESTKGDADSQIA 169

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173742 [Multi-domain] Cd Length: 309 Bit Score: 63.15 E-value: 6.09e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRRQQVAPRAGTPG-----FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG 315
Cdd:cd07845   148 KIADFGLARTYGLPAKPMTPKvvtlwYRAPELLLGCTTYTTAIDMWAVGCILAELLAHK-PLLPGKSEIEQLDLIIQLLG 226


                  .
gi 1034562195 316 S 316
Cdd:cd07845   227 T 227

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270823 [Multi-domain] Cd Length: 282 Bit Score: 62.11 E-value: 1.23e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEH--ESFLDILNS-LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFG 81
Cdd:cd07829    67 IHTENKLYLVFEYCDQdlKKYLDKRPGpLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDgvLK---LADFG 143


                  ..
gi 1034562195  82 LA 83
Cdd:cd07829   144 LA 145

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270832 [Multi-domain] Cd Length: 291 Bit Score: 61.04 E-value: 2.66e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195  18 PYLEHE--SFLD-ILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 83
Cdd:cd07840    84 EYMDHDltGLLDnPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDgvLK---LADFGLA 151

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270908 [Multi-domain] Cd Length: 247 Bit Score: 59.59 E-value: 6.01e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY-NRRLKKYALVDFGL 82
Cdd:cd14006    58 YESPTELVLILELCSGGELLDRLAergSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLaDRPSPQIKIIDFGL 137


                  ..
gi 1034562195  83 AQ 84
Cdd:cd14006   138 AR 139

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

Pssm-ID: 271001 [Multi-domain] Cd Length: 258 Bit Score: 59.49 E-value: 6.21e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDF 80
Cdd:cd14099    69 CFEDEENVYILLELCSNGSLMELLkrrKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDEnmNVK---IGDF 145


                  ...
gi 1034562195  81 GLA 83
Cdd:cd14099   146 GLA 148

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270687 [Multi-domain] Cd Length: 258 Bit Score: 59.41 E-value: 7.95e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195 256 RAGTPGFRAPEVLTKCPNqTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05117   161 VCGTPYYVAPEVLKGKGY-GKKCDIWSLGVILYILLCGYPPFY 202

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270687 [Multi-domain] Cd Length: 258 Bit Score: 59.03 E-value: 1.04e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195  10 NDHVVIAMPYLEH-ESFLDIL--NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYA--LVDFGLA 83
Cdd:cd05117    71 DKNLYLVMELCTGgELFDRIVkkGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDSPikIIDFGLA 149

tRNA A-37 threonylcarbamoyl transferase component Bud32 [Translation, ribosomal structure and biogenesis]; tRNA A-37 threonylcarbamoyl transferase component Bud32 is part of the Pathway/BioSystem: tRNA modification

Pssm-ID: 442859 [Multi-domain] Cd Length: 159 Bit Score: 56.89 E-value: 1.06e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195  14 VIAMPYLEHESFLDILNSLSFQEvrEYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlkKYALVDFGLAQ 84
Cdd:COG3642    32 DLVMEYIEGETLADLLEEGELPP--ELLRELGRLLARLHRAGIVHGDLTTSNILVDDG--GVYLIDFGLAR 98

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270725 [Multi-domain] Cd Length: 350 Bit Score: 59.22 E-value: 1.43e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNSLS-FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVD 79
Cdd:cd05573    68 YAFQDEDHLYLVMEYMPGGDLMNLLIKYDvFPEetARFYIAELVLALDSLHKLGFIHRDIKPDNILLDADghIK---LAD 144

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1034562195  80 FGLAQGTHDTKIELLKFVQSEAQQERCSQNKSH 112
Cdd:cd05573   145 FGLCTKMNKSGDRESYLNDSVNTLFQDNVLARR 177

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270910 [Multi-domain] Cd Length: 267 Bit Score: 57.95 E-value: 2.52e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   9 KNDHVVIAMPYLEHESFLDI-----LNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYN--RRLKkyaLVDFG 81
Cdd:cd14008    77 ESDKLYLVLEYCEGGPVMELdsgdrVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTadGTVK---ISDFG 153

                          90
                  ....*....|....
gi 1034562195  82 LAQGTHDTKIELLK 95
Cdd:cd14008   154 VSEMFEDGNDTLQK 167

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270762 [Multi-domain] Cd Length: 263 Bit Score: 57.49 E-value: 3.01e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYL---EHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVD 79
Cdd:cd05611    64 YSFQSKDYLYLVMEYLnggDCASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTghLK---LTD 140


                  ....*
gi 1034562195  80 FGLAQ 84
Cdd:cd05611   141 FGLSR 145

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270832 [Multi-domain] Cd Length: 291 Bit Score: 57.19 E-value: 5.79e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07840   171 YRPPELLLGATRYGPEVDMWSVGCILAELFTGK-PIFQGKTELEQLEKIFELCGS 224

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143363 [Multi-domain] Cd Length: 337 Bit Score: 57.38 E-value: 5.84e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSR-----RQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLsGRYPFYKASDDLTALAQIMTIRG 315
Cdd:cd07858   148 KICDFGLARttsekGDFMTEYVVTRWYRAPELLLNCSEYTTAIDVWSVGCIFAELL-GRKPLFPGKDYVHQLKLITELLG 226


                  .
gi 1034562195 316 S 316
Cdd:cd07858   227 S 227

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271033 [Multi-domain] Cd Length: 271 Bit Score: 56.45 E-value: 7.75e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY-NRRLKkyaLVDFGLA 83
Cdd:cd14131    98 KPIDPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANFLLvKGRLK---LIDFGIA 149

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270823 [Multi-domain] Cd Length: 282 Bit Score: 56.72 E-value: 7.87e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 247 LSRRQQVAPRAGTPG-----FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGsretiq 321
Cdd:cd07829   144 LARAFGIPLRTYTHEvvtlwYRAPEILLGSKHYSTAVDIWSVGCIFAELITGK-PLFPGDSEIDQLFKIFQILG------ 216

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 322 aaktfgksilcskevpaqdlrklcerlrgmdssTPklTSDIQghashqPAISEKTDHKASClvqtppgqysgNSFKKGDS 401
Cdd:cd07829   217 ---------------------------------TP--TEESW------PGVTKLPDYKPTF-----------PKWPKNDL 244

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034562195 402 NSCEHCFDEYNTNLegwnevpdeaydlLDKLLDLNPASRITAEEALLHPFF 452
Cdd:cd07829   245 EKVLPRLDPEGIDL-------------LSKMLQYNPAKRISAKEALKHPYF 282

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271039 [Multi-domain] Cd Length: 293 Bit Score: 56.74 E-value: 7.90e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  36 EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR---RLKkyaLVDFGLAQ 84
Cdd:cd14137   107 YVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLVDPetgVLK---LCDFGSAK 155

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270997 [Multi-domain] Cd Length: 258 Bit Score: 56.18 E-value: 8.88e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHESFLD-ILNSLSFQEV--REYMLNLFKALKRIHQFGIVHRDVKPSNFL------YNRRLKkyaLVDFG 81
Cdd:cd14095    71 TELYLVMELVKGGDLFDaITSSTKFTERdaSRMVTDLAQALKYLHSLSIVHRDIKPENLLvvehedGSKSLK---LADFG 147


                  ...
gi 1034562195  82 LAQ 84
Cdd:cd14095   148 LAT 150

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270985 [Multi-domain] Cd Length: 259 Bit Score: 56.23 E-value: 9.52e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDlTALAQIMtiRGSRE-------TI-QAAKTFGKS 329
Cdd:cd14083   164 GTPGYVAPEVLAQKP-YGKAVDCWSIGVISYILLCGYPPFYDENDS-KLFAQIL--KAEYEfdspywdDIsDSAKDFIRH 239


                  ...
gi 1034562195 330 ILC 332
Cdd:cd14083   240 LME 242

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173742 [Multi-domain] Cd Length: 309 Bit Score: 56.61 E-value: 9.61e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHE--SFLD-ILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQG 85
Cdd:cd07845    81 DSIFLVMEYCEQDlaSLLDnMPTPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKgcLK---IADFGLART 157


                  ...
gi 1034562195  86 THD 88
Cdd:cd07845   158 YGL 160

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270909 [Multi-domain] Cd Length: 253 Bit Score: 55.56 E-value: 1.36e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLKkyaLVDF 80
Cdd:cd14007    68 YFEDKKRIYLILEYAPNGELYKELKKqkrFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILlgSNGELK---LADF 144


                  ...
gi 1034562195  81 GLA 83
Cdd:cd14007   145 GWS 147

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270825 [Multi-domain] Cd Length: 282 Bit Score: 55.36 E-value: 1.72e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKyaLVDFGLAQGTHDT 89
Cdd:cd07831    97 LPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKDDILK--LADFGSCRGIYSK 152

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173750 [Multi-domain] Cd Length: 332 Bit Score: 55.87 E-value: 1.79e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 229 PASLTCDCYATDKVCSICLSRRQQVAPRAGTP---------GFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLsGRYPFYK 299
Cdd:cd07857   133 PGNLLVNADCELKICDFGLARGFSENPGENAGfmteyvatrWYRAPEIMLSFQSYTKAIDVWSVGCILAELL-GRKPVFK 211

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1034562195 300 ASDDLTALAQIMTIRGS--RETI-----QAAKTFGKS 329
Cdd:cd07857   212 GKDYVDQLNQILQVLGTpdEETLsrigsPKAQNYIRS 248

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270841 [Multi-domain] Cd Length: 337 Bit Score: 56.03 E-value: 1.80e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195  41 MLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLA 83
Cdd:cd07852   113 MYQLLKALKYLHSGGVIHRDLKPSNILLNSdcRVK---LADFGLA 154

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270908 [Multi-domain] Cd Length: 247 Bit Score: 54.97 E-value: 2.01e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTalaqIMTIRGSR---------ETIQAAKTFGK 328
Cdd:cd14006   152 GTPEFVAPEIVNGEP-VSLATDMWSIGVLTYVLLSGLSPFLGEDDQET----LANISACRvdfseeyfsSVSQEAKDFIR 226


                  ....
gi 1034562195 329 SILC 332
Cdd:cd14006   227 KLLV 230

Catalytic domain of the Serine/Threonine kinase, Plant SNT7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNT7 is a plant thylakoid-associated kinase that is essential in short- and long-term acclimation responses to cope with various light conditions in order to maintain photosynthetic redox poise for optimal photosynthetic performance. Short-term response involves state transitions over periods of minutes while the long-term response (LTR) occurs over hours to days and involves changing the relative amounts of photosystems I and II. SNT7 acts as a redox sensor and a signal transducer for both responses, which are triggered by the redox state of the plastoquinone (PQ) pool. It is positioned at the top of a phosphorylation cascade that induces state transitions by phosphorylating light-harvesting complex II (LHCII), and triggers the LTR through the phosphorylation of chloroplast proteins. The SNT7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270915 [Multi-domain] Cd Length: 318 Bit Score: 55.52 E-value: 2.27e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA 83
Cdd:cd14013   122 IKSIMRQILVALRKLHSTGIVHRDVKPQNIIVSEGDGQFKIIDLGAA 168

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270828 [Multi-domain] Cd Length: 329 Bit Score: 55.22 E-value: 2.56e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRRQQVAPRAG-------TPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTI 313
Cdd:cd07834   143 KICDFGLARGVDPDEDKGflteyvvTRWYRAPELLLSSKKYTKAIDIWSVGCIFAELLTRK-PLFPGRDYIDQLNLIVEV 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 314 RGSRetiqaaktfgksilcskevPAQDLRKLC-----ERLRGMDSSTPKLTSDIQGHASHQpAIsektDHKASCLVqtpp 388
Cdd:cd07834   222 LGTP-------------------SEEDLKFISsekarNYLKSLPKKPKKPLSEVFPGASPE-AI----DLLEKMLV---- 273

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195 389 gqysgnsfkkgdsnscehcFdeyntnlegwnevpdeaydlldklldlNPASRITAEEALLHPFFKD 454
Cdd:cd07834   274 -------------------F---------------------------NPKKRITADEALAHPYLAQ 293

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271068 [Multi-domain] Cd Length: 285 Bit Score: 55.00 E-value: 2.74e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 176 NIHSSISHESPAVKLMKQSKTVD-VLSRKLATKKKA--ISTKVM--------NSAVMRKTASSCPASLTCDCYATDKVCS 244
Cdd:cd14166    67 DIYESTTHYYLVMQLVSGGELFDrILERGVYTEKDAsrVINQVLsavkylheNGIVHRDLKPENLLYLTPDENSKIMITD 146

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195 245 ICLSRRQQ---VAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASD 302
Cdd:cd14166   147 FGLSKMEQngiMSTACGTPGYVAPEVLAQKP-YSKAVDCWSIGVITYILLCGYPPFYEETE 206

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270905 [Multi-domain] Cd Length: 252 Bit Score: 54.45 E-value: 2.79e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFG 81
Cdd:cd14003    68 IETENKIYLVMEYASGGELFDYIVNngrLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLdkNGNLK---IIDFG 144


                  ..
gi 1034562195  82 LA 83
Cdd:cd14003   145 LS 146

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270783 [Multi-domain] Cd Length: 258 Bit Score: 54.45 E-value: 3.44e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNSL-SFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKky 75
Cdd:cd06606    62 VRYlgTERTENTLNIFLEYVPGGSLASLLKKFgKLPEpvVRKYTRQILEGLEYLHSNGIVHRDIKGANILVdsDGVVK-- 139


                  ....*...
gi 1034562195  76 aLVDFGLA 83
Cdd:cd06606   140 -LADFGCA 146

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173748 [Multi-domain] Cd Length: 372 Bit Score: 55.14 E-value: 4.15e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRRQQVAPRAG------TPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFyKASDDLTALAQIMTIR 314
Cdd:cd07853   143 KICDFGLARVEEPDESKHmtqevvTQYYRAPEILMGSRHYTSAVDIWSVGCIFAELLGRRILF-QAQSPIQQLDLITDLL 221


                  ..
gi 1034562195 315 GS 316
Cdd:cd07853   222 GT 223

Signaling protein combining a Ser/Thr protein kinase domain and the GUN4/Ycf53 porphyrin-binding domain [Signal transduction mechanisms];

Pssm-ID: 444462 [Multi-domain] Cd Length: 466 Bit Score: 55.40 E-value: 4.18e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGL 82
Cdd:COG5752   106 YFEQDQRLYLVQEFIEGQTLAQELEKkgvFSESQIWQLLKDLLPVLQFIHSRNVIHRDIKPANIIRRRSDGKLVLIDFGV 185


                  ....*....
gi 1034562195  83 AQGTHDTKI 91
Cdd:COG5752   186 AKLLTITAL 194

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270993 [Multi-domain] Cd Length: 291 Bit Score: 54.56 E-value: 4.42e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  12 HVVIAMPYLEHESFLD-ILN--SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY---NRRLKKYALVDFGLA 83
Cdd:cd14091    68 SVYLVTELLRGGELLDrILRqkFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYadeSGDPESLRICDFGFA 145

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270826 [Multi-domain] Cd Length: 287 Bit Score: 54.26 E-value: 4.46e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  13 VVIAMPYLE---HESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 83
Cdd:cd07832    75 FVLVFEYMLsslSEVLRDEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTgvLK---IADFGLA 147

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270828 [Multi-domain] Cd Length: 329 Bit Score: 54.45 E-value: 5.24e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHesflD---ILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGL 82
Cdd:cd07834    77 NDVYIVTELMET----DlhkVIKSpqpLTDDHIQYFLYQILRGLKYLHSAGVIHRDLKPSNILVNSncDLK---ICDFGL 149


                  ...
gi 1034562195  83 AQG 85
Cdd:cd07834   150 ARG 152

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270797 [Multi-domain] Cd Length: 254 Bit Score: 53.77 E-value: 5.27e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNSLS-FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKky 75
Cdd:cd06627    62 VKYigSVKTKDSLYIILEYVENGSLASIIKKFGkFPEslVAVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDglVK-- 139


                  ....*....
gi 1034562195  76 aLVDFGLAQ 84
Cdd:cd06627   140 -LADFGVAT 147

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132943 [Multi-domain] Cd Length: 256 Bit Score: 53.81 E-value: 5.42e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILN----SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRrlKKYA 76
Cdd:cd06612    61 VKYygSYFKNTDLWIVMEYCGAGSVSDIMKitnkTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNE--EGQA 138

                          90
                  ....*....|....
gi 1034562195  77 -LVDFGLAQGTHDT 89
Cdd:cd06612   139 kLADFGVSGQLTDT 152

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270842 [Multi-domain] Cd Length: 336 Bit Score: 54.29 E-value: 6.00e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLsGRYPFYKASDDLTALAQIMTIRGSretiqaaktfgksilcskevPAQDL 341
Cdd:cd07855   179 YRAPELMLSLPEYTQAIDMWSVGCIFAEML-GRRQLFPGKNYVHQLQLILTVLGT--------------------PSQAV 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 342 --RKLCERLRGMdsstpkltsdIQGHASHQPAISEKTDHKASClvqtppgqysgnsfkkgdsnscehcfdeyntnlegwn 419
Cdd:cd07855   238 inAIGADRVRRY----------IQNLPNKQPVPWETLYPKADQ------------------------------------- 270

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1034562195 420 evpdEAYDLLDKLLDLNPASRITAEEALLHPFFK 453
Cdd:cd07855   271 ----QALDLLSQMLRFDPSERITVAEALQHPFLA 300

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270996 [Multi-domain] Cd Length: 300 Bit Score: 54.08 E-value: 6.63e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1034562195 256 RAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDL 304
Cdd:cd14094   172 RVGTPHFMAPEVVKREP-YGKPVDVWGCGVILFILLSGCLPFYGTKERL 219

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270898 [Multi-domain] Cd Length: 273 Bit Score: 53.84 E-value: 6.64e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHESFLDILNSLSF------QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQ 84
Cdd:cd13996    77 PPLYIQMELCEGGTLRDWIDRRNSsskndrKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFLDNDDLQVKIGDFGLAT 156

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1034562195  85 GTHDTKIELLKFVQSEAQqeRCSQNKSHIIT 115
Cdd:cd13996   157 SIGNQKRELNNLNNNNNG--NTSNNSVGIGT 185

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270919 [Multi-domain] Cd Length: 263 Bit Score: 53.42 E-value: 7.14e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  46 KALKRIHQFGIVHRDVKPSNF---LYNRRLKKYALVDFGLAQgthdtkiellKFVQSEAQQERCSQNKSH 112
Cdd:cd14017   108 KAIEDIHEVGFLHRDVKPSNFaigRGPSDERTVYILDFGLAR----------QYTNKDGEVERPPRNAAG 167

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270841 [Multi-domain] Cd Length: 337 Bit Score: 53.72 E-value: 9.85e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG--SRETIQAAKT-FGKSIL 331
Cdd:cd07852   178 YRAPEILLGSTRYTKGVDMWSVGCILGEMLLGK-PLFPGTSTLNQLEKIIEVIGrpSAEDIESIQSpFAATML 249

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270918 [Multi-domain] Cd Length: 266 Bit Score: 52.84 E-value: 1.14e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKYCFRKNDHVVIAMPYLEHeSFLDILN----SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLKKYA 76
Cdd:cd14016    61 LYWFGQEGDYNVMVMDLLGP-SLEDLFNkcgrKFSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLmgLGKNSNKVY 139


                  ....*..
gi 1034562195  77 LVDFGLA 83
Cdd:cd14016   140 LIDFGLA 146

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270824 [Multi-domain] Cd Length: 283 Bit Score: 52.92 E-value: 1.15e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEhESFLDILNS-----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVD 79
Cdd:cd07830    67 FRENDELYFVFEYME-GNLYQLMKDrkgkpFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPevVK---IAD 142


                  ....
gi 1034562195  80 FGLA 83
Cdd:cd07830   143 FGLA 146

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271000 [Multi-domain] Cd Length: 265 Bit Score: 52.86 E-value: 1.27e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR---RLKKYAlvDF 80
Cdd:cd14098    70 YEDDQHIYLVMEYVEGGDLMDFImawGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQddpVIVKIS--DF 147


                  ....*..
gi 1034562195  81 GLAQGTH 87
Cdd:cd14098   148 GLAKVIH 154

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270752 [Multi-domain] Cd Length: 328 Bit Score: 53.08 E-value: 1.31e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNS----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLV 78
Cdd:cd05601    68 YAFQDSENLYLVMEYHPGGDLLSLLSRyddiFEESMARFYLAELVLAIHSLHSMGYVHRDIKPENILIDRTghIK---LA 144


                  ....*
gi 1034562195  79 DFGLA 83
Cdd:cd05601   145 DFGSA 149

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173741 [Multi-domain] Cd Length: 293 Bit Score: 53.00 E-value: 1.33e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRRQQVAPRAGTPG-----FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKasddltalaqimtirG 315
Cdd:cd07843   146 KICDFGLAREYGSPLKPYTQLvvtlwYRAPELLLGAKEYSTAIDMWSVGCIFAELLTKK-PLFP---------------G 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 316 SRETIQAAKTFgksilcskevpaqdlrKLCerlrgmdsSTPklTSDIQGHASHQPAISEKTdhkasclVQTPPGQYSGNS 395
Cdd:cd07843   210 KSEIDQLNKIF----------------KLL--------GTP--TEKIWPGFSELPGAKKKT-------FTKYPYNQLRKK 256

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195 396 FKKGDSNscEHCFDEYNTNLEgwnevpdeaydlldklldLNPASRITAEEALLHPFF 452
Cdd:cd07843   257 FPALSLS--DNGFDLLNRLLT------------------YDPAKRISAEDALKHPYF 293

Kae1-associated kinase Bud32;

Pssm-ID: 237847 [Multi-domain] Cd Length: 211 Bit Score: 51.83 E-value: 1.36e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  14 VIAMPYLEHESFLDILNSLSfQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYaLVDFGLAQGTHD 88
Cdd:PRK14879   75 IIVMEYIEGEPLKDLINSNG-MEELELSREIGRLVGKLHSAGIIHGDLTTSNMILSGG-KIY-LIDFGLAEFSKD 146

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271064 [Multi-domain] Cd Length: 259 Bit Score: 52.30 E-value: 1.53e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  13 VVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQGTH 87
Cdd:cd14162    75 VYIIMELAENGDLLDYIRKngaLPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKnnNLK---ITDFGFARGVM 151


                  ...
gi 1034562195  88 DTK 90
Cdd:cd14162   152 KTK 154

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270839 [Multi-domain] Cd Length: 336 Bit Score: 53.08 E-value: 1.70e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  19 YLEHE---SFLDILNSLSFQE------VREYM-LNLFK---------------------ALKRIHQFGIVHRDVKPSNFL 67
Cdd:cd07849    59 RFKHEniiGILDIQRPPTFESfkdvyiVQELMeTDLYKliktqhlsndhiqyflyqilrGLKYIHSANVLHRDLKPSNLL 138

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1034562195  68 YNRR--LKkyaLVDFGLAQGT---HDTKIELLKFV 97
Cdd:cd07849   139 LNTNcdLK---ICDFGLARIAdpeHDHTGFLTEYV 170

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270826 [Multi-domain] Cd Length: 287 Bit Score: 52.33 E-value: 2.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 229 PASLTCDCYATDKVCSICLSR------RQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASD 302
Cdd:cd07832   128 PANLLISSTGVLKIADFGLARlfseedPRLYSHQVATRWYRAPELLYGSRKYDEGVDLWAVGCIFAELLNGS-PLFPGEN 206

                          90
                  ....*....|....
gi 1034562195 303 DLTALAQIMTIRGS 316
Cdd:cd07832   207 DIEQLAIVLRTLGT 220

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270895 [Multi-domain] Cd Length: 267 Bit Score: 51.97 E-value: 2.29e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEH-ESFLDILNSLSFQE----VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFG 81
Cdd:cd13993    74 FETEVAIYIVLEYCPNgDLFEAITENRIYVGktelIKNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDEGTVKLCDFG 153


                  ..
gi 1034562195  82 LA 83
Cdd:cd13993   154 LA 155

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271069 [Multi-domain] Cd Length: 263 Bit Score: 51.95 E-value: 2.32e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASD 302
Cdd:cd14167   165 GTPGYVAPEVLAQKP-YSKAVDCWSIGVIAYILLCGYPPFYDEND 208

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270995 [Multi-domain] Cd Length: 272 Bit Score: 51.97 E-value: 2.64e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195 258 GTPGFRAPEVLtKC------PNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd14093   170 GTPGYLAPEVL-KCsmydnaPGYGKEVDMWACGVIMYTLLAGCPPFW 215

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270948 [Multi-domain] Cd Length: 278 Bit Score: 51.99 E-value: 2.85e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  15 IAMPYLEHESFLDILNSLSFQEVREyMLNLFK----ALKRIHQFGIVHRDVKPSN-FLYNRRLKKYAlvDFGLAQgTHDT 89
Cdd:cd14046    81 IQMEYCEKSTLRDLIDSGLFQDTDR-LWRLFRqileGLAYIHSQGIIHRDLKPVNiFLDSNGNVKIG--DFGLAT-SNKL 156


                  ....*.
gi 1034562195  90 KIELLK 95
Cdd:cd14046   157 NVELAT 162

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270896 [Multi-domain] Cd Length: 265 Bit Score: 51.54 E-value: 3.03e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVD 79
Cdd:cd13994    65 LCQDLHGKWCLVMEYCPGGDLFTLIekaDSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDgvLK---LTD 141


                  ....*
gi 1034562195  80 FGLAQ 84
Cdd:cd13994   142 FGTAE 146

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270833 [Multi-domain] Cd Length: 298 Bit Score: 51.80 E-value: 3.22e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195 259 TPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSgRYPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07841   165 TRWYRAPELLFGARHYGVGVDMWSVGCIFAELLL-RVPFLPGDSDIDQLGKIFEALGT 221

serine/threonine-protein kinase 1; Provisional

Pssm-ID: 223069 [Multi-domain] Cd Length: 267 Bit Score: 51.40 E-value: 3.30e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFG 81
Cdd:PHA03390   76 YSVTTLKGHVLIMDYIKDGDLFDLLkkeGKLSEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVLYDRAKDRIYLCDYG 155

                          90
                  ....*....|....*.
gi 1034562195  82 LAQ---------GTHD 88
Cdd:PHA03390  156 LCKiigtpscydGTLD 171

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270995 [Multi-domain] Cd Length: 272 Bit Score: 51.59 E-value: 3.41e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  27 DILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLA 83
Cdd:cd14093    98 DYLTEvvtLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDNL-NVKISDFGFA 156

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143385 [Multi-domain] Cd Length: 343 Bit Score: 51.88 E-value: 3.50e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG--SRETIQA-----AKTFGKSIlcsK 334
Cdd:cd07880   181 YRAPEVILNWMHYTQTVDIWSVGCIMAEMLTGK-PLFKGHDHLDQLMEIMKVTGtpSKEFVQKlqsedAKNYVKKL---P 256

                          90
                  ....*....|
gi 1034562195 335 EVPAQDLRKL 344
Cdd:cd07880   257 RFRKKDFRSL 266

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270749 [Multi-domain] Cd Length: 333 Bit Score: 51.55 E-value: 4.92e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNSLS-FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVD 79
Cdd:cd05598    68 YSFQDKENLYFVMDYIPGGDLMSLLIKKGiFEEdlARFYIAELVCAIESVHKMGFIHRDIKPDNILIDRdgHIK---LTD 144

                          90
                  ....*....|....
gi 1034562195  80 FGLAQG---THDTK 90
Cdd:cd05598   145 FGLCTGfrwTHDSK 158

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143341 [Multi-domain] Cd Length: 284 Bit Score: 50.94 E-value: 5.12e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG--SRETIQAAKTFGKSILCSKEVPAQ 339
Cdd:cd07836   166 YRAPDVLLGSRTYSTSIDIWSVGCIMAEMITGR-PLFPGTNNEDQLLKIFRIMGtpTESTWPGISQLPEYKPTFPRYPPQ 244


                  ....*
gi 1034562195 340 DLRKL 344
Cdd:cd07836   245 DLQQL 249

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270987 [Multi-domain] Cd Length: 294 Bit Score: 50.98 E-value: 5.24e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd14085   162 GTPGYCAPEILRGCA-YGPEVDMWSVGVITYILLCGFEPFYDERGD 206

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271039 [Multi-domain] Cd Length: 293 Bit Score: 50.96 E-value: 5.44e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 263 RAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG--SRETIQAAKtfgksilcskevpaqd 340
Cdd:cd14137   173 RAPELIFGATDYTTAIDIWSAGCVLAELLLGQ-PLFPGESSVDQLVEIIKVLGtpTREQIKAMN---------------- 235

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 341 lrklcerlrgmDSSTPKLTSDIQGHaSHQPAISEKTDHKASCLVqtppgqysgnsfkkgdsnscEHCFdEYNtnlegwne 420
Cdd:cd14137   236 -----------PNYTEFKFPQIKPH-PWEKVFPKRTPPDAIDLL--------------------SKIL-VYN-------- 274

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1034562195 421 vpdeaydlldklldlnPASRITAEEALLHPFFKD 454
Cdd:cd14137   275 ----------------PSKRLTALEALAHPFFDE 292

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270899 [Multi-domain] Cd Length: 252 Bit Score: 50.84 E-value: 5.49e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  10 NDHVVIAMPYLEHESFLDILNSLSFQ------EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFG 81
Cdd:cd13997    72 GGHLYIQMELCENGSLQDALEELSPIsklseaEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKgtCK---IGDFG 148


                  ..
gi 1034562195  82 LA 83
Cdd:cd13997   149 LA 150

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270796 [Multi-domain] Cd Length: 265 Bit Score: 50.76 E-value: 6.47e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  11 DHVVIAMPYLEH---ESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLKkyaLVDFGLA 83
Cdd:cd06626    72 EEVYIFMEYCQEgtlEELLRHGRILDEAVIRVYTLQLLEGLAYLHENGIVHRDIKPANIFldSNGLIK---LGDFGSA 146

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270775 [Multi-domain] Cd Length: 382 Bit Score: 51.20 E-value: 6.62e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNSLS-FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05625    68 YSFQDKDNLYFVMDYIPGGDMMSLLIRMGvFPEdlARFYIAELTCAVESVHKMGFIHRDIKPDNILIDRD-GHIKLTDFG 146

                          90
                  ....*....|..
gi 1034562195  82 LAQG---THDTK 90
Cdd:cd05625   147 LCTGfrwTHDSK 158

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271100 [Multi-domain] Cd Length: 270 Bit Score: 50.31 E-value: 7.69e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTAL--AQImTIRGSRETI----QAAKTFGKSIL 331
Cdd:cd14198   174 GTPEYLAPEILNYDP-ITTATDMWNIGVIAYMLLTHESPFVGEDNQETFLniSQV-NVDYSEETFssvsQLATDFIQKLL 251

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270778 [Multi-domain] Cd Length: 377 Bit Score: 51.00 E-value: 7.76e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDIL-NSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05629    68 YSFQDAQYLYLIMEFLPGGDLMTMLiKYDTFSEdvTRFYMAECVLAIEAVHKLGFIHRDIKPDNILIDRG-GHIKLSDFG 146

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1034562195  82 LAQG---THDTKIELLKFVQSEAQQERCSQN 109
Cdd:cd05629   147 LSTGfhkQHDSAYYQKLLQGKSNKNRIDNRN 177

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270887 [Multi-domain] Cd Length: 272 Bit Score: 50.41 E-value: 7.97e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  13 VVIAMPYLEhESFLDILNS-----LSFQEVREYMLNLFKALKRIHQFG--IVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:cd13985    77 VLLLMEYCP-GSLVDILEKsppspLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNT-GRFKLCDFGSA 152

cyclin-dependent protein kinase; Provisional

Pssm-ID: 240233 [Multi-domain] Cd Length: 335 Bit Score: 50.53 E-value: 8.80e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 234 CDCYATDKVCSICLSRRQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTI 313
Cdd:PTZ00024  171 YPPYSDTLSKDETMQRREEMTSKVVTLWYRAPELLMGAEKYHFAVDMWSVGCIFAELLTGK-PLFPGENEIDQLGRIFEL 249


                  ....*.
gi 1034562195 314 RGSRET 319
Cdd:PTZ00024  250 LGTPNE 255

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270836 [Multi-domain] Cd Length: 286 Bit Score: 50.50 E-value: 9.12e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHeSFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGL 82
Cdd:cd07846    69 FRRKKRWYLVFEFVDH-TVLDDLekypNGLDESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQS-GVVKLCDFGF 146


                  ..
gi 1034562195  83 AQ 84
Cdd:cd07846   147 AR 148

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270853 [Multi-domain] Cd Length: 288 Bit Score: 50.01 E-value: 1.06e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  13 VVIAMPYLEHE--SFLDIL-NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd07871    78 LTLVFEYLDSDlkQYLDNCgNLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEK-GELKLADFGLAR 151

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270988 [Multi-domain] Cd Length: 292 Bit Score: 50.11 E-value: 1.10e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195 257 AGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKaSDDLTALAQIMT 312
Cdd:cd14086   164 AGTPGYLSPEVLRKDP-YGKPVDIWACGVILYILLVGYPPFWD-EDQHRLYAQIKA 217

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270849 [Multi-domain] Cd Length: 311 Bit Score: 50.01 E-value: 1.18e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  17 MPYLEHEsFLDILNSLSFQ----EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQGTHDTK 90
Cdd:cd07866    94 TPYMDHD-LSGLLENPSVKltesQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQgiLK---IADFGLARPYDGPP 169

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270789 [Multi-domain] Cd Length: 255 Bit Score: 49.52 E-value: 1.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDIL--NSLSFQE------VREymlnLFKALKRIHQFGIVHRDVKPSNFLYNR-- 70
Cdd:cd06614    59 VDYydSYLVGDELWVVMEYMDGGSLTDIItqNPVRMNEsqiayvCRE----VLQGLEYLHSQNVIHRDIKSDNILLSKdg 134

                          90
                  ....*....|....*..
gi 1034562195  71 RLKkyaLVDFGL-AQGT 86
Cdd:cd06614   135 SVK---LADFGFaAQLT 148

Serine/threonine-protein kinase SNT7; Provisional

Pssm-ID: 215638 [Multi-domain] Cd Length: 566 Bit Score: 50.56 E-value: 1.30e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA 83
Cdd:PLN03225  257 IQTIMRQILFALDGLHSTGIVHRDVKPQNIIFSEGSGSFKIIDLGAA 303

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173715 [Multi-domain] Cd Length: 381 Bit Score: 50.40 E-value: 1.34e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNSLS-FQEV--REYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05626    68 YSFQDKDNLYFVMDYIPGGDMMSLLIRMEvFPEVlaRFYIAELTLAIESVHKMGFIHRDIKPDNILIDLD-GHIKLTDFG 146

                          90
                  ....*....|..
gi 1034562195  82 LAQG---THDTK 90
Cdd:cd05626   147 LCTGfrwTHNSK 158

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270878 [Multi-domain] Cd Length: 242 Bit Score: 49.35 E-value: 1.34e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1034562195 256 RAGTPGFRAPEVLtkCPNQT---TAIDMWSAGVIFLSLLSGRYPFYKA 300
Cdd:cd13976   146 KHGCPAYVSPEIL--NSGATysgKAADVWSLGVILYTMLVGRYPFHDS 191

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270747 [Multi-domain] Cd Length: 352 Bit Score: 50.07 E-value: 1.38e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDF 80
Cdd:cd05596    93 YAFQDDKYLYMVMDYMPGGDLVNLMSNYDVPEkwARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDASghLK---LADF 169


                  .
gi 1034562195  81 G 81
Cdd:cd05596   170 G 170

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270905 [Multi-domain] Cd Length: 252 Bit Score: 49.44 E-value: 1.40e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14003   160 GTPAYAAPEVLLGRKYDGPKADVWSLGVILYAMLTGYLPF 199

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270760 [Multi-domain] Cd Length: 280 Bit Score: 49.71 E-value: 1.57e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YC-FRKNDHVVIAMPYLEH---ESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNrRLKKYALVDF 80
Cdd:cd05609    66 YCsFETKRHLCMVMEYVEGgdcATLLKNIGPLPVDMARMYFAETVLALEYLHSYGIVHRDLKPDNLLIT-SMGHIKLTDF 144


                  ....
gi 1034562195  81 GLAQ 84
Cdd:cd05609   145 GLSK 148

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270839 [Multi-domain] Cd Length: 336 Bit Score: 50.00 E-value: 1.58e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 233 TCDCyatdKVCSICLSRrqQVAPRAGTPGF----------RAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASD 302
Cdd:cd07849   142 NCDL----KICDFGLAR--IADPEHDHTGFlteyvatrwyRAPEIMLNSKGYTKAIDIWSVGCILAEMLSNR-PLFPGKD 214

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1034562195 303 DLTALAQIMTIRG--SRETIQA-----AKTFGKSILCSKEVPAQDL 341
Cdd:cd07849   215 YLHQLNLILGILGtpSQEDLNCiislkARNYIKSLPFKPKVPWNKL 260

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

Pssm-ID: 270901 [Multi-domain] Cd Length: 245 Bit Score: 49.07 E-value: 1.67e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRRQQVAP-----RAGTPGFRAPEVLTKCPNqTTAIDMWSAGVIFLSLLSGRYPFykasDDLTALAQIMTI-- 313
Cdd:cd13999   131 KIADFGLSRIKNSTTekmtgVVGTPRWMAPEVLRGEPY-TEKADVYSFGIVLWELLTGEVPF----KELSPIQIAAAVvq 205


                  ....*....
gi 1034562195 314 RGSRETIQA 322
Cdd:cd13999   206 KGLRPPIPP 214

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

Pssm-ID: 270693 [Multi-domain] Cd Length: 250 Bit Score: 49.05 E-value: 1.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   4 KYCFRKNDHVVIAMPYL---EHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLV 78
Cdd:cd05123    59 HYAFQTEEKLYLVLDYVpggELFSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDghIK---LT 135


                  ....*
gi 1034562195  79 DFGLA 83
Cdd:cd05123   136 DFGLA 140

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270829 [Multi-domain] Cd Length: 283 Bit Score: 49.21 E-value: 1.82e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 83
Cdd:cd07835   101 IKSYLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEgaLK---LADFGLA 146

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270989 [Multi-domain] Cd Length: 259 Bit Score: 49.07 E-value: 1.82e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14087   163 GTPEYIAPEILLRKP-YTQSVDMWAVGVIAYILLSGTMPF 201

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271084 [Multi-domain] Cd Length: 276 Bit Score: 49.14 E-value: 1.90e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195 239 TDKVCSICLSRRQQVAPRAGTPGFRAPEVLtKC------PNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd14182   152 TDFGFSCQLDPGEKLREVCGTPGYLAPEII-ECsmddnhPGYGKEVDMWSTGVIMYTLLAGSPPFW 216

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270835 [Multi-domain] Cd Length: 286 Bit Score: 49.30 E-value: 1.91e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 83
Cdd:cd07844    93 GGLSMHNVRLFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERgeLK---LADFGLA 145

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271083 [Multi-domain] Cd Length: 279 Bit Score: 49.20 E-value: 2.09e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195 258 GTPGFRAPEVLtKC------PNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd14181   177 GTPGYLAPEIL-KCsmdethPGYGKEVDLWACGVILFTLLAGSPPFW 222

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270761 [Multi-domain] Cd Length: 349 Bit Score: 49.49 E-value: 2.10e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYL---EHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05610    71 YSLQSANNVYLVMEYLiggDVKSLLHIYGYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNE-GHIKLTDFG 149

                          90
                  ....*....|...
gi 1034562195  82 LAQGTHDTKIELL 94
Cdd:cd05610   150 LSKVTLNRELNMM 162

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271035 [Multi-domain] Cd Length: 262 Bit Score: 48.80 E-value: 2.12e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 236 CYATDKVCSICLSRRqqvapragtpgFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGrYPFYKASDDLTALAQIMTIRG 315
Cdd:cd14133   152 CFLTQRLYSYIQSRY-----------YRAPEVILGLP-YDEKIDMWSLGCILAELYTG-EPLFPGASEVDQLARIIGTIG 218


                  .
gi 1034562195 316 S 316
Cdd:cd14133   219 I 219

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270838 [Multi-domain] Cd Length: 287 Bit Score: 49.22 E-value: 2.13e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKYCFRKNDHVVIAMPYLEhESFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLKkya 76
Cdd:cd07848    65 LKEAFRRRGKLYLVFEYVE-KNMLELLeempNGVPPEKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLisHNDVLK--- 140


                  ....*...
gi 1034562195  77 LVDFGLAQ 84
Cdd:cd07848   141 LCDFGFAR 148

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270842 [Multi-domain] Cd Length: 336 Bit Score: 49.29 E-value: 2.45e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQG 85
Cdd:cd07855   106 LTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNEncELK---IGDFGMARG 158

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270852 [Multi-domain] Cd Length: 286 Bit Score: 48.80 E-value: 2.60e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 229 PASLTCDCYATDKVCSICLSRR-----QQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd07870   126 PQNLLISYLGELKLADFGLARAksipsQTYSSEVVTLWYRPPDVLLGATDYSSALDIWGAGCIFIEMLQGQPAFPGVSDV 205

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 304 LTALAQIMTIRGsretiqaaktfgksilcskeVPAQDLrklcerlrgmdsstpkltsdiqghashQPAISEKTDHKASCL 383
Cdd:cd07870   206 FEQLEKIWTVLG--------------------VPTEDT---------------------------WPGVSKLPNYKPEWF 238

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195 384 VQTPPGQYSgnsfkkgdsnscehcfdeyntnlEGWNEV--PDEAYDLLDKLLDLNPASRITAEEALLHPFF 452
Cdd:cd07870   239 LPCKPQQLR-----------------------VVWKRLsrPPKAEDLASQMLMMFPKDRISAQDALLHPYF 286

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143359 [Multi-domain] Cd Length: 342 Bit Score: 49.01 E-value: 2.88e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 259 TPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDdltaLAQIMTIRGSretiqaaktfgksilcskeVPA 338
Cdd:cd07854   181 TKWYRSPRLLLSPNNYTKAIDMWAAGCIFAEMLTGKPLFAGAHE----LEQMQLILES-------------------VPV 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 339 QDLRKLCERLRGMDSSTPKLTSDIqghasHQPaisektdhkascLVQTPPgqysgnsfkkgdsnscehcfdeyntnlegw 418
Cdd:cd07854   238 VREEDRNELLNVIPSFVRNDGGEP-----RRP------------LRDLLP------------------------------ 270

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1034562195 419 nEVPDEAYDLLDKLLDLNPASRITAEEALLHPFFKDMS 456
Cdd:cd07854   271 -GVNPEALDFLEQILTFNPMDRLTAEEALMHPYMSCYS 307

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270776 [Multi-domain] Cd Length: 366 Bit Score: 49.29 E-value: 2.93e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05627    69 YSFQDKRNLYLIMEFLPGGDMMTLLmkkDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLLDAK-GHVKLSDFG 147


                  ....
gi 1034562195  82 LAQG 85
Cdd:cd05627   148 LCTG 151

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143356 [Multi-domain] Cd Length: 343 Bit Score: 49.21 E-value: 2.99e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG--SRETIQ-----AAKTFGKS 329
Cdd:cd07851   181 YRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGK-TLFPGSDHIDQLKRIMNLVGtpDEELLKkisseSARNYIQS 254

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143383 [Multi-domain] Cd Length: 343 Bit Score: 48.89 E-value: 3.16e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLAQGTHD 88
Cdd:cd07878   115 LSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDC-ELRILDFGLARQADD 170

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270750 [Multi-domain] Cd Length: 324 Bit Score: 48.76 E-value: 3.59e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   4 KYCFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLV 78
Cdd:cd05599    67 YYSFQDEENLYLIMEFLPGGDMMTLLmkkDTLTEEETRFYIAETVLAIESIHKLGYIHRDIKPDNLLLDARghIK---LS 143


                  ....*....
gi 1034562195  79 DFGLAQGTH 87
Cdd:cd05599   144 DFGLCTGLK 152

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143344 [Multi-domain] Cd Length: 284 Bit Score: 48.58 E-value: 3.59e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  25 FLDILN-SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQ 84
Cdd:cd07839    88 YFDSCNgDIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNgeLK---LADFGLAR 147

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270833 [Multi-domain] Cd Length: 298 Bit Score: 48.72 E-value: 3.66e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEheSFLDIL---NSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLV 78
Cdd:cd07841    70 VFGHKSNINLVFEFME--TDLEKVikdKSIVLTPadIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASdgVLK---LA 144


                  ....*
gi 1034562195  79 DFGLA 83
Cdd:cd07841   145 DFGLA 149

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270994 [Multi-domain] Cd Length: 311 Bit Score: 48.45 E-value: 3.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 259 TPGFR----APEVLTKCPNQTT---AIDMWSAGVIFLSLLSGRYPFYKASDDLTAlAQIMT-IRGSRETI---------Q 321
Cdd:cd14092   160 TPCFTlpyaAPEVLKQALSTQGydeSCDLWSLGVILYTMLSGQVPFQSPSRNESA-AEIMKrIKSGDFSFdgeewknvsS 238

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034562195 322 AAKTFGKSILC---SKEVPAQDLRKlCERLRGMDS--STPKLTSDIQGHASHQPAISEKTDHKA 380
Cdd:cd14092   239 EAKSLIQGLLTvdpSKRLTMSELRN-HPWLQGSSSpsSTPLMTPGVLSSSAAAVSTALRATFDA 301

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271005 [Multi-domain] Cd Length: 250 Bit Score: 47.99 E-value: 4.11e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASD 302
Cdd:cd14103   154 GTPEFVAPEVVNYEP-ISYATDMWSVGVICYVLLSGLSPFMGDND 197

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270911 [Multi-domain] Cd Length: 251 Bit Score: 47.99 E-value: 4.11e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYAL--VDFGLAQ 84
Cdd:cd14009    94 ARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLSTSGDDPVLkiADFGFAR 143

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143356 [Multi-domain] Cd Length: 343 Bit Score: 48.44 E-value: 4.27e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQGTHD 88
Cdd:cd07851   115 LSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEdcELK---ILDFGLARHTDD 170

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270729 [Multi-domain] Cd Length: 278 Bit Score: 48.29 E-value: 4.35e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 247 LSRRQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF-----YKASDDLTALAQIMTIRGSRETIQ 321
Cdd:cd05577   145 FKGGKKIKGRVGTHGYMAPEVLQKEVAYDFSVDWFALGCMLYEMIAGRSPFrqrkeKVDKEELKRRTLEMAVEYPDSFSP 224

                          90       100
                  ....*....|....*....|
gi 1034562195 322 AAKTFGKSILCSKevPAQDL 341
Cdd:cd05577   225 EARSLCEGLLQKD--PERRL 242

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270730 [Multi-domain] Cd Length: 257 Bit Score: 48.02 E-value: 4.60e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 247 LSRRQQVAPRAGTPGFRAPEVLtKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKAS 301
Cdd:cd05578   150 LTDGTLATSTSGTKPYMAPEVF-MRAGYSFAVDWWSLGVTAYEMLRGKRPYEIHS 203

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270971 [Multi-domain] Cd Length: 261 Bit Score: 47.71 E-value: 4.87e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034562195  35 QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 83
Cdd:cd14069   100 DVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLLDENdnLK---ISDFGLA 147

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270912 [Multi-domain] Cd Length: 269 Bit Score: 48.06 E-value: 5.12e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  24 SFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGLA 83
Cdd:cd14010    80 DLETLLRQdgnLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLdgNGTLK---LSDFGLA 141

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271016 [Multi-domain] Cd Length: 259 Bit Score: 47.96 E-value: 5.20e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY-NRRLKKYALVDFG 81
Cdd:cd14114    68 FEDDNEMVLILEFLSGGELFERIaaehYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCtTKRSNEVKLIDFG 147

                          90       100
                  ....*....|....*....|.
gi 1034562195  82 LAqgTHDTKIELLKFVQSEAQ 102
Cdd:cd14114   148 LA--THLDPKESVKVTTGTAE 166

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270896 [Multi-domain] Cd Length: 265 Bit Score: 47.69 E-value: 5.32e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd13994   164 GSEPYMAPEVFTSGSYDGRAVDVWSCGIVLFALFTGRFPWRSAKKS 209

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143363 [Multi-domain] Cd Length: 337 Bit Score: 48.14 E-value: 5.76e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQGTHDT 89
Cdd:cd07858   104 TLSDDHCQYFLYQLLRGLKYIHSANVLHRDLKPSNLLLNANcdLK---ICDFGLARTTSEK 161

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173686 [Multi-domain] Cd Length: 323 Bit Score: 48.08 E-value: 6.08e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD-LTALAQIMTIRGSRETIQAAKTFGKSILcsKEV 336
Cdd:cd05595   157 GTPEYLAPEVLED-NDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHErLFELILMEEIRFPRTLSPEAKSLLAGLL--KKD 233

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 337 PAQDL------------RKLCERLRGMDSSTPKLTSDIqghashQPAISEKTDHK-------ASCLVQTPPGQYS 392
Cdd:cd05595   234 PKQRLgggpsdakevmeHRFFLSINWQDVVQKKLLPPF------KPQVTSEVDTRyfddeftAQSITITPPDRYD 302

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270986 [Multi-domain] Cd Length: 275 Bit Score: 47.77 E-value: 6.43e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 256 RAGTPGFRAPEVLTKCPNQ--TTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRgsretiqaaKTFGKSILCS 333
Cdd:cd14084   173 LCGTPTYLAPEVLRSFGTEgyTRAVDCWSLGVILFICLSGYPPFSEEYTQMSLKEQILSGK---------YTFIPKAWKN 243

                          90
                  ....*....|
gi 1034562195 334 KEVPAQDLRK 343
Cdd:cd14084   244 VSEEAKDLVK 253

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270991 [Multi-domain] Cd Length: 263 Bit Score: 47.67 E-value: 6.67e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  36 EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR-----LKkyaLVDFGLAQGTHDTK 90
Cdd:cd14089   101 EAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSKgpnaiLK---LTDFGFAKETTTKK 157

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

Pssm-ID: 270901 [Multi-domain] Cd Length: 245 Bit Score: 47.15 E-value: 6.70e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   9 KNDHVVIAMPYLEHESFLDILNS----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGL 82
Cdd:cd13999    61 SPPPLCIVTEYMPGGSLYDLLHKkkipLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLdeNFTVK---IADFGL 137


                  ..
gi 1034562195  83 AQ 84
Cdd:cd13999   138 SR 139

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270777 [Multi-domain] Cd Length: 376 Bit Score: 48.11 E-value: 6.74e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05628    68 YSFQDKLNLYLIMEFLPGGDMMTLLmkkDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSK-GHVKLSDFG 146


                  ....
gi 1034562195  82 LAQG 85
Cdd:cd05628   147 LCTG 150

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271093 [Multi-domain] Cd Length: 259 Bit Score: 47.31 E-value: 7.04e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL-YNRRLKKYALVDFGLAQ 84
Cdd:cd14191    97 LTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMcVNKTGTKIKLIDFGLAR 150

Stk1 family PASTA domain-containing Ser/Thr kinase;

Pssm-ID: 468045 [Multi-domain] Cd Length: 563 Bit Score: 48.25 E-value: 7.57e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  10 NDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyalV-DFGLA 83
Cdd:NF033483   79 GGIPYIVMEYVDGRTLKDYIREhgpLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKdgRVK----VtDFGIA 154

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271022 [Multi-domain] Cd Length: 256 Bit Score: 46.98 E-value: 8.36e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL-----------YNRR 71
Cdd:cd14120    60 CQETSSSVYLVMEYCNGGDLADYLQAkgtLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILlshnsgrkpspNDIR 139

                          90
                  ....*....|....*...
gi 1034562195  72 LKkyaLVDFGLAQGTHDT 89
Cdd:cd14120   140 LK---IADFGFARFLQDG 154

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

Pssm-ID: 270693 [Multi-domain] Cd Length: 250 Bit Score: 47.13 E-value: 8.86e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034562195 257 AGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05123   154 CGTPEYLAPEVLLGKG-YGKAVDWWSLGVLLYEMLTGKPPFY 194

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270984 [Multi-domain] Cd Length: 260 Bit Score: 47.02 E-value: 9.03e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEVL-TKCPNQTtaIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14082   167 GTPAYLAPEVLrNKGYNRS--LDMWSVGVIIYVSLSGTFPF 205

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271037 [Multi-domain] Cd Length: 318 Bit Score: 47.22 E-value: 9.58e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTHDTKI 91
Cdd:cd14135   102 LNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVNEKKNTLKLCDFGSASDIGENEI 161

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270843 [Multi-domain] Cd Length: 328 Bit Score: 47.57 E-value: 9.90e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  35 QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQ 84
Cdd:cd07856   108 QFIQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENcdLK---ICDFGLAR 156

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

Pssm-ID: 271001 [Multi-domain] Cd Length: 258 Bit Score: 46.78 E-value: 1.04e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14099   163 GTPNYIAPEVLEKKKGHSFEVDIWSLGVILYTLLVGKPPF 202

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271095 [Multi-domain] Cd Length: 261 Bit Score: 46.83 E-value: 1.04e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEH-ESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL-YNRRLKKYALVDFG 81
Cdd:cd14193    70 FESRNDIVLVMEYVDGgELFDRIIDenyNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILcVSREANQVKIIDFG 149


                  ...
gi 1034562195  82 LAQ 84
Cdd:cd14193   150 LAR 152

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271070 [Multi-domain] Cd Length: 301 Bit Score: 46.96 E-value: 1.08e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASD 302
Cdd:cd14168   172 GTPGYVAPEVLAQKP-YSKAVDCWSIGVIAYILLCGYPPFYDEND 215

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143341 [Multi-domain] Cd Length: 284 Bit Score: 47.09 E-value: 1.10e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQ 84
Cdd:cd07836   102 VKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRgeLK---LADFGLAR 148

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270854 [Multi-domain] Cd Length: 297 Bit Score: 46.92 E-value: 1.11e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195  27 DILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQG 85
Cdd:cd07873    92 DCGNSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINER-GELKLADFGLARA 149

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271091 [Multi-domain] Cd Length: 255 Bit Score: 46.84 E-value: 1.19e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLA 83
Cdd:cd14189    70 FEDAENIYIFLELCSRKSLAHIWkarHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENM-ELKVGDFGLA 148

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271090 [Multi-domain] Cd Length: 255 Bit Score: 46.54 E-value: 1.23e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLA 83
Cdd:cd14188    70 FEDKENIYILLEYCSRRSMAHILKArkvLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENM-ELKVGDFGLA 148

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270994 [Multi-domain] Cd Length: 311 Bit Score: 46.91 E-value: 1.24e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  12 HVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY-----NRRLKkyaLVDFGLA 83
Cdd:cd14092    73 HTYLVMELLRGGELLERIrkkKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFtdeddDAEIK---IVDFGFA 149

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143382 [Multi-domain] Cd Length: 345 Bit Score: 46.96 E-value: 1.35e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLAQGTHD 88
Cdd:cd07877   117 LTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDC-ELKILDFGLARHTDD 172

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271071 [Multi-domain] Cd Length: 277 Bit Score: 46.42 E-value: 1.43e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASD 302
Cdd:cd14169   164 GTPGYVAPELLEQKP-YGKAVDVWAIGVISYILLCGYPPFYDEND 207

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271063 [Multi-domain] Cd Length: 255 Bit Score: 46.49 E-value: 1.54e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:cd14161    71 FENSSKIVIVMEYASRGDLYDYISErqrLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDAN-GNIKIADFGLS 149


                  ....*..
gi 1034562195  84 QGTHDTK 90
Cdd:cd14161   150 NLYNQDK 156

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143384 [Multi-domain] Cd Length: 342 Bit Score: 46.82 E-value: 1.54e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  15 IAMPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQ 84
Cdd:cd07879    97 LVMPYMQTDLQKIMGHPLSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAVNEdcELK---ILDFGLAR 165

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271008 [Multi-domain] Cd Length: 268 Bit Score: 46.19 E-value: 1.66e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195 241 KVCSICLSR----RQQVAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFykASDD 303
Cdd:cd14106   151 KLCDFGISRvigeGEEIREILGTPDYVAPEILSYEP-ISLATDMWSIGVLTYVLLTGHSPF--GGDD 214

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270910 [Multi-domain] Cd Length: 267 Bit Score: 46.39 E-value: 1.74e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034562195 253 VAPRAGTPGFRAPEVLTK--CPNQTTAIDMWSAGVIFLSLLSGRYPFYKAS 301
Cdd:cd14008   165 LQKTAGTPAFLAPELCDGdsKTYSGKAADIWALGVTLYCLVFGRLPFNGDN 215

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270904 [Multi-domain] Cd Length: 253 Bit Score: 46.09 E-value: 1.76e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEHESFlDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDF 80
Cdd:cd14002    68 SFETKKEFVVVTEYAQGELF-QILEddgTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIgkGGVVK---LCDF 143


                  ...
gi 1034562195  81 GLA 83
Cdd:cd14002   144 GFA 146

Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271126 [Multi-domain] Cd Length: 380 Bit Score: 46.66 E-value: 1.76e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCpNQTTAIDMWSAGVIFLSLLSGrYPFYKASDDLTALAQIMTIRG-----SRETIQAAKTF 326
Cdd:cd14224   233 YRAPEVILGA-RYGMPIDMWSFGCILAELLTG-YPLFPGEDEGDQLACMIELLGmppqkLLETSKRAKNF 300

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271087 [Multi-domain] Cd Length: 258 Bit Score: 46.09 E-value: 1.92e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  25 FLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR---RLKKYALVDFGLAQ 84
Cdd:cd14185    86 FDAIIESVKFTEhdAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHnpdKSTTLKLADFGLAK 150

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

Pssm-ID: 274749 [Multi-domain] Cd Length: 199 Bit Score: 45.28 E-value: 1.92e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  14 VIAMPYLEHESFLDILNSLSFqevrEYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYaLVDFGLAQGTH---DTK 90
Cdd:TIGR03724  73 TIVMEYIEGKPLKDVIEENGD----ELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD-KVY-LIDFGLGKYSDeieDKA 146


                  ....*....
gi 1034562195  91 IELLKFVQS 99
Cdd:TIGR03724 147 VDLHVLKRS 155

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270782 [Multi-domain] Cd Length: 265 Bit Score: 45.80 E-value: 2.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDhVVIAMPYLEHESF-----------LDILNSLSFQEVreymlnlfKALKRIH-QFGIVHRDVKPSNFLYNRR-- 71
Cdd:cd06605    68 FYSEGD-ISICMEYMDGGSLdkilkevgripERILGKIAVAVV--------KGLIYLHeKHKIIHRDVKPSNILVNSRgq 138

                          90
                  ....*....|
gi 1034562195  72 LKkyaLVDFG 81
Cdd:cd06605   139 VK---LCDFG 145

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270852 [Multi-domain] Cd Length: 286 Bit Score: 46.11 E-value: 2.15e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNrRLKKYALVDFGLAQ 84
Cdd:cd07870   100 VRLFMFQLLRGLAYIHGQHILHRDLKPQNLLIS-YLGELKLADFGLAR 146

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271086 [Multi-domain] Cd Length: 259 Bit Score: 45.79 E-value: 2.23e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195  43 NLFKALKRIHQFGIVHRDVKPSNFL---YNRRLKKYALVDFGLA 83
Cdd:cd14184   107 NLASALKYLHGLCIVHRDIKPENLLvceYPDGTKSLKLGDFGLA 150

glycogen synthase kinase; Provisional

Pssm-ID: 173333 [Multi-domain] Cd Length: 440 Bit Score: 46.57 E-value: 2.59e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGrYPFYKASDDLTALAQIMTIRGSrETIQAAKTFGKSILCSK--EVPAQ 339
Cdd:PTZ00036  236 YRAPELMLGATNYTTHIDLWSLGCIIAEMILG-YPIFSGQSSVDQLVRIIQVLGT-PTEDQLKEMNPNYADIKfpDVKPK 313


                  ....*
gi 1034562195 340 DLRKL 344
Cdd:PTZ00036  314 DLKKV 318

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271099 [Multi-domain] Cd Length: 271 Bit Score: 45.70 E-value: 2.69e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195 232 LTCDCYATD-KVCSICLSR----RQQVAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14197   144 LTSESPLGDiKIVDFGLSRilknSEELREIMGTPEYVAPEILSYEP-ISTATDMWSIGVLAYVMLTGISPF 213

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271013 [Multi-domain] Cd Length: 257 Bit Score: 45.58 E-value: 2.76e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 251 QQVAPRAGTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPFYKASDDLTAlAQIMTIRGSR-----ETIQAAKT 325
Cdd:cd14111   155 RQLGRRTGTLEYMAPEMVKGEPVGPPA-DIWSIGVLTYIMLSGRSPFEDQDPQETE-AKILVAKFDAfklypNVSQSASL 232


                  ....*...
gi 1034562195 326 FGKSILCS 333
Cdd:cd14111   233 FLKKVLSS 240

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270792 [Multi-domain] Cd Length: 286 Bit Score: 45.89 E-value: 2.76e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEHESFLDIL------NSLSFQEVREYMLNLFKALKRIHQfgIVHRDVKPSNFLYNRRlKKYALVD 79
Cdd:cd06620    72 FLNENNNIIICMEYMDCGSLDKILkkkgpfPEEVLGKIAVAVLEGLTYLYNVHR--IIHRDIKPSNILVNSK-GQIKLCD 148


                  ....
gi 1034562195  80 FGLA 83
Cdd:cd06620   149 FGVS 152

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271010 [Multi-domain] Cd Length: 255 Bit Score: 45.66 E-value: 2.85e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNSLSF--QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL-YNRRLKKYALVDFGLA 83
Cdd:cd14108    67 FEKRRVVIIVTELCHEELLERITKRPTVceSEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLmADQKTDQVRICDFGNA 146


                  .
gi 1034562195  84 Q 84
Cdd:cd14108   147 Q 147

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271133 [Multi-domain] Cd Length: 256 Bit Score: 45.47 E-value: 2.85e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195 256 RAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYkaSDDLTALAQ 309
Cdd:cd14663   162 TCGTPNYVAPEVLARRGYDGAKADIWSCGVILFVLLAGYLPFD--DENLMALYR 213

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271023 [Multi-domain] Cd Length: 252 Bit Score: 45.36 E-value: 2.88e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR----LKkyaLVDFGLAQ 84
Cdd:cd14121    97 VRRFLQQLASALQFLREHNISHMDLKPQNLLLSSRynpvLK---LADFGFAQ 145

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143384 [Multi-domain] Cd Length: 342 Bit Score: 46.05 E-value: 3.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFyKASDDLTALAQIMTIRG--SRETIQ-----AAKTFGKSIlcsK 334
Cdd:cd07879   180 YRAPEVILNWMHYNQTVDIWSVGCIMAEMLTGKTLF-KGKDYLDQLTQILKVTGvpGPEFVQkledkAAKSYIKSL---P 255

                          90
                  ....*....|
gi 1034562195 335 EVPAQDLRKL 344
Cdd:cd07879   256 KYPRKDFSTL 265

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270741 [Multi-domain] Cd Length: 326 Bit Score: 45.75 E-value: 3.13e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd05589   163 GTPEFLAPEVLTD-TSYTRAVDWWGLGVLIYEMLVGESPF 201

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271074 [Multi-domain] Cd Length: 267 Bit Score: 45.37 E-value: 3.32e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195  35 QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKK--YALVDFGLAQGT 86
Cdd:cd14172   103 REASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTSKEKDavLKLTDFGFAKET 156

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270889 [Multi-domain] Cd Length: 259 Bit Score: 45.39 E-value: 3.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSN-FLYNRRLKKYALVDFGL 82
Cdd:cd13987    60 FETEDYYVFAQEYAPYGDLFSIIppqVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENvLLFDKDCRRVKLCDFGL 139


                  ..
gi 1034562195  83 AQ 84
Cdd:cd13987   140 TR 141

glycogen synthase kinase; Provisional

Pssm-ID: 173333 [Multi-domain] Cd Length: 440 Bit Score: 45.80 E-value: 3.52e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKND-----HVVIA-MP-----YLEHESFLDilNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKK 74
Cdd:PTZ00036  132 CFKKNEkniflNVVMEfIPqtvhkYMKHYARNN--HALPLFLVKLYSYQLCRALAYIHSKFICHRDLKPQNLLIDPNTHT 209

                          90
                  ....*....|
gi 1034562195  75 YALVDFGLAQ 84
Cdd:PTZ00036  210 LKLCDFGSAK 219

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143359 [Multi-domain] Cd Length: 342 Bit Score: 45.54 E-value: 3.57e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQ 84
Cdd:cd07854   109 GPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFINTEDLVLKIGDFGLAR 163

cyclin-dependent kinase A; Provisional

Pssm-ID: 177649 [Multi-domain] Cd Length: 294 Bit Score: 45.19 E-value: 3.89e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQ 84
Cdd:PLN00009  104 IKTYLYQILRGIAYCHSHRVLHRDLKPQNLLIDRRTNALKLADFGLAR 151

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271071 [Multi-domain] Cd Length: 277 Bit Score: 45.27 E-value: 4.10e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  12 HVVIAMPYLEHESFLD-ILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLK--KYALVDFGLAQ 84
Cdd:cd14169    75 HLYLAMELVTGGELFDrIIERGSYTEkdASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYATPFEdsKIMISDFGLSK 152

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271011 [Multi-domain] Cd Length: 255 Bit Score: 45.20 E-value: 4.14e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRR----QQVAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYkASDDLTALAQIMTIRGS 316
Cdd:cd14109   138 KLADFGQSRRllrgKLTTLIYGSPEFVSPEIVNSYP-VTLATDMWSVGVLTYVLLGGISPFL-GDNDRETLTNVRSGKWS 215

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143385 [Multi-domain] Cd Length: 343 Bit Score: 45.33 E-value: 4.18e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQGT 86
Cdd:cd07880   115 LSEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEdcELK---ILDFGLARQT 168

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270824 [Multi-domain] Cd Length: 283 Bit Score: 45.22 E-value: 4.36e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07830   164 YRAPEILLRSTSYSSPVDIWALGCIMAELYTLR-PLFPGSSEIDQLYKICSVLGT 217

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270772 [Multi-domain] Cd Length: 405 Bit Score: 45.77 E-value: 4.43e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDF 80
Cdd:cd05622   140 YAFQDDRYLYMVMEYMPGGDLVNLMSNYDVPEkwARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKsgHLK---LADF 216


                  .
gi 1034562195  81 G 81
Cdd:cd05622   217 G 217

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270855 [Multi-domain] Cd Length: 258 Bit Score: 44.76 E-value: 4.76e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNSLS-----FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSN-FL-YNRR 71
Cdd:cd08215    62 VKYyeSFEENGKLCIVMEYADGGDLAQKIKKQKkkgqpFPEeqILDWFVQICLALKYLHSRKILHRDLKTQNiFLtKDGV 141

                          90
                  ....*....|..
gi 1034562195  72 LKkyaLVDFGLA 83
Cdd:cd08215   142 VK---LGDFGIS 150

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270847 [Multi-domain] Cd Length: 302 Bit Score: 45.18 E-value: 4.86e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  19 YLEHEsFLDILNS--LSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd07864    97 YMDHD-LMGLLESglVHFSEdhIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNK-GQIKLADFGLAR 164

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271127 [Multi-domain] Cd Length: 341 Bit Score: 45.08 E-value: 5.03e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195 262 FRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGrYPFYKASDDLTALAQIMTIRG 315
Cdd:cd14225   211 YRSPEVILGLP-YSMAIDMWSLGCILAELYTG-YPLFPGENEVEQLACIMEVLG 262

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270821 [Multi-domain] Cd Length: 297 Bit Score: 44.98 E-value: 5.15e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKAS 301
Cdd:cd06659   179 GTPYWMAPEVISRCP-YGTEVDIWSLGIMVIEMVDGEPPYFSDS 221

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173748 [Multi-domain] Cd Length: 372 Bit Score: 45.12 E-value: 5.17e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQ 84
Cdd:cd07853    99 PLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSncVLK---ICDFGLAR 151

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270902 [Multi-domain] Cd Length: 275 Bit Score: 44.91 E-value: 5.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF---YKASDDLTALAQIMTIRGSRETIQAAKTFGKSILCSK 334
Cdd:cd14000   177 GTPGFRAPEIARGNVIYNEKVDVFSFGMLLYEILSGGAPMvghLKFPNEFDIHGGLRPPLKQYECAPWPEVEVLMKKCWK 256


                  ....*
gi 1034562195 335 EVPAQ 339
Cdd:cd14000   257 ENPQQ 261

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270834 [Multi-domain] Cd Length: 316 Bit Score: 44.97 E-value: 5.31e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLtalaqimtirgsretiqaaktfgksilcSKEVPAQD- 340
Cdd:cd07842   181 YRAPELLLGARHYTKAIDIWAIGCIFAELLTLEPIFKGREAKI----------------------------KKSNPFQRd 232

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 341 -LRKLCERLrGMdsSTPKLTSDIQGHASHQPAISektdhkasclvQTPPGQYsgnsfkkgDSNSCEHCFDEyntnlegWN 419
Cdd:cd07842   233 qLERIFEVL-GT--PTEKDWPDIKKMPEYDTLKS-----------DTKASTY--------PNSLLAKWMHK-------HK 283

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1034562195 420 EVPDEAYDLLDKLLDLNPASRITAEEALLHPFF 452
Cdd:cd07842   284 KPDSQGFDLLRKLLEYDPTKRITAEEALEHPYF 316

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270793 [Multi-domain] Cd Length: 287 Bit Score: 44.72 E-value: 5.35e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  15 IAMPYLEHESFLDILNSLSFQEVR--EYML-----NLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:cd06621    78 IAMEYCEGGSLDSIYKKVKKKGGRigEKVLgkiaeSVLKGLSYLHSRKIIHRDIKPSNILLTRK-GQVKLCDFGVS 152

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173715 [Multi-domain] Cd Length: 381 Bit Score: 45.39 E-value: 5.36e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQImtirGSRETIQAAktfgKSILCSKEvp 337
Cdd:cd05626   210 GTPNYIAPEVLLR-KGYTQLCDWWSVGVILFEMLVGQPPFLAPTPTETQLKVI----NWENTLHIP----PQVKLSPE-- 278

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 338 AQDL-RKLC----ERL--RGMDS-------STPKLTSDIQGH-ASHQPAISEKTDHKASCLV--QTPPGQYSGNSFKKGD 400
Cdd:cd05626   279 AVDLiTKLCcsaeERLgrNGADDikahpffSEVDFSSDIRTQpAPYVPKISHPMDTSNFDPVeeESPWNDASGDSTRTWD 358

                         170
                  ....*....|....*..
gi 1034562195 401 ------SNSCEHCFDEY 411
Cdd:cd05626   359 tlcspnGKHPEHAFYEF 375

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271135 [Multi-domain] Cd Length: 257 Bit Score: 44.59 E-value: 5.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSR----RQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDltalaqimtiRGS 316
Cdd:cd14665   138 KICDFGYSKssvlHSQPKSTVGTPAYIAPEVLLKKEYDGKIADVWSCGVTLYVMLVGAYPFEDPEEP----------RNF 207


                  ....*
gi 1034562195 317 RETIQ 321
Cdd:cd14665   208 RKTIQ 212

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270952 [Multi-domain] Cd Length: 249 Bit Score: 44.61 E-value: 5.41e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGL 82
Cdd:cd14050    96 SLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKD-GVCKLGDFGL 146

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271084 [Multi-domain] Cd Length: 276 Bit Score: 44.52 E-value: 5.91e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKYCFRKNDHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVD 79
Cdd:cd14182    75 LKDTYETNTFFFLVFDLMKKGELFDYLTekvTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDDDM-NIKLTD 153


                  ....
gi 1034562195  80 FGLA 83
Cdd:cd14182   154 FGFS 157

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143344 [Multi-domain] Cd Length: 284 Bit Score: 44.73 E-value: 6.05e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07839   165 YRPPDVLFGAKLYSTSIDMWSAGCIFAELANAGRPLFPGNDVDDQLKRIFRLLGT 219

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270867 [Multi-domain] Cd Length: 270 Bit Score: 44.42 E-value: 6.39e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNSLS-----FQEVREY--MLNLFKALKRIH-QFGIVHRDVKPSNFLYNRRl 72
Cdd:cd08528    72 VRYykTFLENDRLYIVMELIEGAPLGEHFSSLKeknehFTEDRIWniFVQMVLALRYLHkEKQIVHRDLKPNNIMLGED- 150

                          90
                  ....*....|..
gi 1034562195  73 KKYALVDFGLAQ 84
Cdd:cd08528   151 DKVTITDFGLAK 162

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270831 [Multi-domain] Cd Length: 287 Bit Score: 44.57 E-value: 6.42e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTaIDMWSAGVIFLSLLSgRYPFYKASDDLTALAQIMTIRGsretiqaaktfgksilcskeVPAQDl 341
Cdd:cd07838   172 YRAPEVLLQSSYATP-VDMWSVGCIFAELFN-RRPLFRGSSEADQLGKIFDVIG--------------------LPSEE- 228

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 342 rklcerlrgmdsSTPKLTSDIQGHASHQPAISEKTDHKASClvqtppgqysgnsfkkgdsnscehcfDEYNTNLEgwnev 421
Cdd:cd07838   229 ------------EWPRNSALPRSSFPSYTPRPFKSFVPEID--------------------------EEGLDLLK----- 265

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1034562195 422 pdeaydlldKLLDLNPASRITAEEALLHPFF 452
Cdd:cd07838   266 ---------KMLTFNPHKRISAFEALQHPYF 287

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270876 [Multi-domain] Cd Length: 290 Bit Score: 44.70 E-value: 6.67e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd13974   195 GSPAYISPDVLSGKPYLGKPSDMWALGVVLFTMLYGQFPFY 235

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270827 [Multi-domain] Cd Length: 288 Bit Score: 44.62 E-value: 6.85e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG 315
Cdd:cd07833   167 YRAPELLVGDTNYGKPVDVWAIGCIMAELLDGE-PLFPGDSDIDQLYLIQKCLG 219

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270848 [Multi-domain] Cd Length: 310 Bit Score: 44.67 E-value: 6.94e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  33 SFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQGthdtkiellkFVQSEAQQERCSQNK 110
Cdd:cd07865   117 TLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDgvLK---LADFGLARA----------FSLAKNSQPNRYTNR 183

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270843 [Multi-domain] Cd Length: 328 Bit Score: 44.87 E-value: 6.98e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 234 CDCyatdKVCSICLSRRQ--QVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIM 311
Cdd:cd07856   145 CDL----KICDFGLARIQdpQMTGYVSTRYYRAPEIMLTWQKYDVEVDIWSAGCIFAEMLEGK-PLFPGKDHVNQFSIIT 219


                  ....*
gi 1034562195 312 TIRGS 316
Cdd:cd07856   220 ELLGT 224

Activator of bc1 complex (ABC1) kinases, also called aarF domain containing kinase 3; This subfamily is composed of the atypical yeast protein kinase Abc1p, its human homolog ADCK3 (also called CABC1), and similar proteins. Abc1p (also called Coq8p) is required for the biosynthesis of Coenzyme Q (ubiquinone or Q), which is an essential lipid component in respiratory electron and proton transport. It is necessary for the formation of a multi-subunit Q-biosynthetic complex and may also function in the regulation of Q synthesis. Human ADCK3 is able to rescue defects in Q synthesis and the phosphorylation state of Coq proteins in yeast Abc1 (or Coq8) mutants. Mutations in ADCK3 cause progressive cerebellar ataxia and atrophy due to Q10 deficiency. In algae and higher plants, ABC1 kinases have proliferated to more than 15 subfamilies, most of which are located in plastids or mitochondria. Subfamily 13 (ABC1K13) of plant ABC1 kinases belongs in this subfamily with yeast Abc1p and human ADCK3. ABC1 kinases are not related to the ATP-binding cassette (ABC) membrane transporter family.

Pssm-ID: 270872 [Multi-domain] Cd Length: 251 Bit Score: 44.04 E-value: 7.18e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  14 VIAMPYLEHESFLDILNsLSfQEVREY----MLNLFkaLKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGL 82
Cdd:cd13970   148 VLTTEFVDGVPLDEAAD-LS-QEERNRigelLLRLC--LRELFEFGFMQTDPNPGNFLYDPEDGRLGLLDFGA 216

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270925 [Multi-domain] Cd Length: 242 Bit Score: 44.27 E-value: 7.57e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195 256 RAGTPGFRAPEVL-TKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKaSDDLTALAQI 310
Cdd:cd14023   146 KHGCPAYVSPEILnTTGTYSGKSADVWSLGVMLYTLLVGRYPFHD-SDPSALFSKI 200

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270822 [Multi-domain] Cd Length: 277 Bit Score: 44.39 E-value: 7.72e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNSLSFQE------VREYMLnlfkALKRIHQFGIVHRDVKPSNFLYNR--RL 72
Cdd:cd06917    65 IKYygSYLKGPSLWIIMDYCEGGSIRTLMRAGPIAEryiaviMREVLV----ALKFIHKDGIIHRDIKAANILVTNtgNV 140

                          90
                  ....*....|.
gi 1034562195  73 KkyaLVDFGLA 83
Cdd:cd06917   141 K---LCDFGVA 148

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271021 [Multi-domain] Cd Length: 255 Bit Score: 44.17 E-value: 7.99e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195  40 YMLNLFKALKRIHQFGIVHRDVKPSNFLYN--RRLKkyaLVDFGLAQ 84
Cdd:cd14119   102 YFVQLIDGLEYLHSQGIIHKDIKPGNLLLTtdGTLK---ISDFGVAE 145

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270771 [Multi-domain] Cd Length: 379 Bit Score: 44.61 E-value: 8.06e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHEsflDILNSLSFQEVRE-----YMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVD 79
Cdd:cd05621   121 FQDDKYLYMVMEYMPGG---DLVNLMSNYDVPEkwakfYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKygHLK---LAD 194


                  ..
gi 1034562195  80 FG 81
Cdd:cd05621   195 FG 196

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270746 [Multi-domain] Cd Length: 356 Bit Score: 44.63 E-value: 8.36e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKAS-DDLTALAQIMTIRGSRETIQAAKTFGKSILcsKEV 336
Cdd:cd05594   188 GTPEYLAPEVLED-NDYGRAVDWWGLGVVMYEMMCGRLPFYNQDhEKLFELILMEEIRFPRTLSPEAKSLLSGLL--KKD 264

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 337 PAQDL------------RKLCERLRGMDSSTPKLTSDIqghashQPAISEKTDHK-------ASCLVQTPPGQysGNSFK 397
Cdd:cd05594   265 PKQRLgggpddakeimqHKFFAGIVWQDVYEKKLVPPF------KPQVTSETDTRyfdeeftAQMITITPPDQ--DDSME 336


                  ....
gi 1034562195 398 KGDS 401
Cdd:cd05594   337 TVDN 340

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270884 [Multi-domain] Cd Length: 269 Bit Score: 44.19 E-value: 8.46e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195 257 AGTPGFRAPEVLT--KCPNQTTAIDMWSAGVIFLSLLS-GRYPF 297
Cdd:cd13982   168 AGTSGWIAPEMLSgsTKRRQTRAVDIFSLGCVFYYVLSgGSHPF 211

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270939 [Multi-domain] Cd Length: 277 Bit Score: 44.20 E-value: 8.81e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  13 VVIAMPYLEHESFLDILNS-----LSFQEVREYMLNLFKALKRIHQFG--IVHRDVKPSNFLYNRRLkKYALVDFGLA 83
Cdd:cd14037    81 VLLLMEYCKGGGVIDLMNQrlqtgLTESEILKIFCDVCEAVAAMHYLKppLIHRDLKVENVLISDSG-NYKLCDFGSA 157

Catalytic domain of the Protein Tyrosine Kinase, Wee1b; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1b (also called Wee2), Xenopus laevis Wee1a (XeWee1a) and similar vertebrate proteins. XeWee1a accumulates after exiting the metaphase II stage in oocytes and in early mitotic cells. It functions during the first zygotic cell division and not during subsequent divisions. Mammalian Wee2/Wee1b is an oocyte-specific inhibitor of meiosis that functions downstream of cAMP. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1b subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271041 [Multi-domain] Cd Length: 274 Bit Score: 44.15 E-value: 9.01e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195   9 KNDHVVIAMPYLEHESFLDIL-------NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRL 72
Cdd:cd14139    71 EDDHMIIQNEYCNGGSLQDAIsentksgNHFEEPELKDILLQVSMGLKYIHNSGLVHLDIKPSNIFICHKM 141

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270986 [Multi-domain] Cd Length: 275 Bit Score: 43.92 E-value: 9.01e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLD-ILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR-----RLKkyaLV 78
Cdd:cd14084    80 FDAEDDYYIVLELMEGGELFDrVVSNKRLKEaiCKLYFYQMLLAVKYLHSNGIIHRDLKPENVLLSSqeeecLIK---IT 156


                  ....*.
gi 1034562195  79 DFGLAQ 84
Cdd:cd14084   157 DFGLSK 162

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270998 [Multi-domain] Cd Length: 295 Bit Score: 44.35 E-value: 9.20e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195 258 GTPGFRAPEVLtKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDL 304
Cdd:cd14096   199 GTVGYTAPEVV-KDERYSKKVDMWALGCVLYTLLCGFPPFYDESIET 244

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270971 [Multi-domain] Cd Length: 261 Bit Score: 43.86 E-value: 9.94e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195 256 RAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASD 302
Cdd:cd14069   162 MCGTLPYVAPELLAKKKYRAEPVDVWSCGIVLFAMLAGELPWDQPSD 208

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271069 [Multi-domain] Cd Length: 263 Bit Score: 43.86 E-value: 1.00e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNSLSF---QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKKYALVDFG 81
Cdd:cd14167    70 YESGGHLYLIMQLVSGGELFDRIVEKGFyteRDASKLIFQILDAVKYLHDMGIVHRDLKPENLLYYSldEDSKIMISDFG 149


                  ...
gi 1034562195  82 LAQ 84
Cdd:cd14167   150 LSK 152

serine/threonine kinase US3; Provisional

Pssm-ID: 165473 [Multi-domain] Cd Length: 392 Bit Score: 44.45 E-value: 1.03e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195   7 FRKNDHVVIAMPYLEHESF--LDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:PHA03207  155 YRWKSTVCMVMPKYKCDLFtyVDRSGPLPLEQAITIQRRLLEALAYLHGRGIIHRDVKTENIFLDEP-ENAVLGDFGAA 232

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143377 [Multi-domain] Cd Length: 309 Bit Score: 44.21 E-value: 1.05e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195  27 DILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQG 85
Cdd:cd07872    96 DCGNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINER-GELKLADFGLARA 153

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271005 [Multi-domain] Cd Length: 250 Bit Score: 43.75 E-value: 1.05e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLE-HESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL-YNRRLKKYALVDFG 81
Cdd:cd14103    59 FETPREMVLVMEYVAgGELFERVVDDdfeLTERDCILFMRQICEGVQYMHKQGILHLDLKPENILcVSRTGNQIKIIDFG 138


                  ...
gi 1034562195  82 LAQ 84
Cdd:cd14103   139 LAR 141

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271087 [Multi-domain] Cd Length: 258 Bit Score: 43.78 E-value: 1.06e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 237 YATDKVCSIClsrrqqvapraGTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIM 311
Cdd:cd14185   151 YVTGPIFTVC-----------GTPTYVAPEILSE-KGYGLEVDMWAAGVILYILLCGFPPFRSPERDQEELFQII 213

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270988 [Multi-domain] Cd Length: 292 Bit Score: 43.95 E-value: 1.08e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195  41 MLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYA--LVDFGLA 83
Cdd:cd14086   106 IQQILESVNHCHQNGIVHRDLKPENLLLASKSKGAAvkLADFGLA 150

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271081 [Multi-domain] Cd Length: 310 Bit Score: 43.88 E-value: 1.11e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKYC--FRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY-----NRRL 72
Cdd:cd14179    65 VKLHevYHDQLHTFLVMELLKGGELLERIKKkqhFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFtdesdNSEI 144

                          90
                  ....*....|..
gi 1034562195  73 KkyaLVDFGLAQ 84
Cdd:cd14179   145 K---IIDFGFAR 153

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173750 [Multi-domain] Cd Length: 332 Bit Score: 43.93 E-value: 1.13e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1034562195  47 ALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQGTHDTKIE 92
Cdd:cd07857   117 GLKYIHSANVLHRDLKPGNLLVNAdcELK---ICDFGLARGFSENPGE 161

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270975 [Multi-domain] Cd Length: 254 Bit Score: 43.53 E-value: 1.17e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFG 81
Cdd:cd14073    70 FENKDKIVIVMEYASGGELYDYISerrRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLdqNGNAK---IADFG 146

                          90
                  ....*....|
gi 1034562195  82 LAQGTHDTKI 91
Cdd:cd14073   147 LSNLYSKDKL 156

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

Pssm-ID: 271112 [Multi-domain] Cd Length: 311 Bit Score: 44.07 E-value: 1.21e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGrYPFYKASDDLTALAQIMTIRG--SRETIQAAK 324
Cdd:cd14210   181 YRAPEVILGLP-YDTAIDMWSLGCILAELYTG-YPLFPGENEEEQLACIMEVLGvpPKSLIDKAS 243

Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 and BubR1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Bub1 (Budding uninhibited by benzimidazoles 1), BubR1, and similar proteins. They contain an N-terminal Bub1/Mad3 homology domain essential for Cdc20 binding and a C-terminal kinase domain. Bub1 and BubR1 are involved in SAC, a surveillance system that delays metaphase to anaphase transition by blocking the activity of APC/C (the anaphase promoting complex) until all chromosomes achieve proper attachments to the mitotic spindle, to avoid chromosome missegregation. Impaired SAC leads to genomic instabilities and tumor development. Bub1 and BubR1 facilitate the localization of SAC proteins to kinetochores and regulate kinetochore-microtubule (K-MT) attachments. Repression studies of Bub1 and BubR1 show that they exert an additive effect in misalignment phenotypes and may function cooperatively or in parallel pathways in regulating K-MT attachments. The Bub1/BubR1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270883 [Multi-domain] Cd Length: 298 Bit Score: 43.88 E-value: 1.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   1 MGVKYCFRKNDHVVIAMPYLEHESFLDILNSL---SFQEVREYM-----LNLFKALKRIHQFGIVHRDVKPSNFL----- 67
Cdd:cd13981    64 SGAHSAHLFQDESILVMDYSSQGTLLDVVNKMknkTGGGMDEPLamfftIELLKVVEALHEVGIIHGDIKPDNFLlrlei 143

                          90       100
                  ....*....|....*....|...
gi 1034562195  68 ---------YNRRLKKYALVDFG 81
Cdd:cd13981   144 cadwpgegeNGWLSKGLKLIDFG 166

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271083 [Multi-domain] Cd Length: 279 Bit Score: 43.81 E-value: 1.30e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLA 83
Cdd:cd14181   112 TLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQL-HIKLSDFGFS 163

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270976 [Multi-domain] Cd Length: 258 Bit Score: 43.56 E-value: 1.35e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTaLAQIMTIR 314
Cdd:cd14074   165 GSLAYSAPEILLGDEYDAPAVDIWSLGVILYMLVCGQPPFQEANDSET-LTMIMDCK 220

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143382 [Multi-domain] Cd Length: 345 Bit Score: 43.88 E-value: 1.35e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 229 PASLTCDCYATDKVCSICLSRR--QQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTA 306
Cdd:cd07877   148 PSNLAVNEDCELKILDFGLARHtdDEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGR-TLFPGTDHIDQ 226

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1034562195 307 LAQIMTIRG-------SRETIQAAKTFGKSI 330
Cdd:cd07877   227 LKLILRLVGtpgaellKKISSESARNYIQSL 257

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270979 [Multi-domain] Cd Length: 267 Bit Score: 43.59 E-value: 1.38e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   2 GVKYCFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkya 76
Cdd:cd14077    77 RLRDFLRTPNHYYMLFEYVDGGQLLDYIishGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILIskSGNIK--- 153


                  ....*..
gi 1034562195  77 LVDFGLA 83
Cdd:cd14077   154 IIDFGLS 160

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271020 [Multi-domain] Cd Length: 275 Bit Score: 43.50 E-value: 1.46e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195 257 AGTPGFRAPEVLTKCPNQTT--AIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14118   176 AGTPAFMAPEALSESRKKFSgkALDIWAMGVTLYCFVFGRCPF 218

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271068 [Multi-domain] Cd Length: 285 Bit Score: 43.44 E-value: 1.47e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195  44 LFKALKRIHQFGIVHRDVKPSNFLY--NRRLKKYALVDFGLAQ 84
Cdd:cd14166   109 VLSAVKYLHENGIVHRDLKPENLLYltPDENSKIMITDFGLSK 151

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271008 [Multi-domain] Cd Length: 268 Bit Score: 43.49 E-value: 1.47e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  21 EHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYN--RRLKKYALVDFGLA 83
Cdd:cd14106    94 ELQTLLDEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTseFPLGDIKLCDFGIS 158

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270840 [Multi-domain] Cd Length: 337 Bit Score: 43.56 E-value: 1.54e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  10 NDHVVIAMPyLEHESfldiLNSLSFQevreyMLNlfkALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQ 84
Cdd:cd07850    90 NLCQVIQMD-LDHER----MSYLLYQ-----MLC---GIKHLHSAGIIHRDLKPSNIVVKSDctLK---ILDFGLAR 150

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271095 [Multi-domain] Cd Length: 261 Bit Score: 43.36 E-value: 1.54e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRRQQvaPRA------GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYkASDDLTALAQIMTIR 314
Cdd:cd14193   144 KIIDFGLARRYK--PREklrvnfGTPEFLAPEVVNY-EFVSFPTDMWSLGVIAYMLLSGLSPFL-GEDDNETLNNILACQ 219

                          90       100
                  ....*....|....*....|...
gi 1034562195 315 GS------RETIQAAKTFGKSIL 331
Cdd:cd14193   220 WDfedeefADISEEAKDFISKLL 242

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132971 [Multi-domain] Cd Length: 277 Bit Score: 43.50 E-value: 1.57e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd06640    71 YLKGTKLWIIMEYLGGGSALDLLRAGPFDEfqIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQ-GDVKLADFGVAG 149

                          90
                  ....*....|...
gi 1034562195  85 GTHDTKIELLKFV 97
Cdd:cd06640   150 QLTDTQIKRNTFV 162

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270990 [Multi-domain] Cd Length: 265 Bit Score: 43.48 E-value: 1.58e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd14088   161 GTPEYLAPEVVGR-QRYGRPVDCWAIGVIMYILLSGNPPFYDEAEE 205

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271040 [Multi-domain] Cd Length: 276 Bit Score: 43.47 E-value: 1.67e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNS-------LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR 70
Cdd:cd14138    68 VRYysAWAEDDHMLIQNEYCNGGSLADAISEnyrimsyFTEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFISR 144

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270980 [Multi-domain] Cd Length: 257 Bit Score: 43.14 E-value: 1.70e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLA 83
Cdd:cd14078    96 DRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEdqNLK---LIDFGLC 148

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271072 [Multi-domain] Cd Length: 303 Bit Score: 43.48 E-value: 1.74e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195  35 QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKK--YALVDFGLAQGT 86
Cdd:cd14170   101 REASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNaiLKLTDFGFAKET 154

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271098 [Multi-domain] Cd Length: 269 Bit Score: 43.02 E-value: 1.75e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14196   173 GTPEFVAPEIVNYEPLGLEA-DMWSIGVITYILLSGASPF 211

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270750 [Multi-domain] Cd Length: 324 Bit Score: 43.37 E-value: 1.78e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYkaSDDLTALAQimTIRGSRETIQaaktFGKSILCSKEvp 337
Cdd:cd05599   162 GTPDYIAPEVFLQ-KGYGKECDWWSLGVIMYEMLIGYPPFC--SDDPQETCR--KIMNWRETLV----FPPEVPISPE-- 230

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1034562195 338 AQDL-RKLC----ERL--RGMDsstpkltsDIQGH 365
Cdd:cd05599   231 AKDLiERLLcdaeHRLgaNGVE--------EIKSH 257

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270846 [Multi-domain] Cd Length: 290 Bit Score: 43.10 E-value: 1.82e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195  35 QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd07862   110 ETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSS-GQIKLADFGLAR 158

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271096 [Multi-domain] Cd Length: 269 Bit Score: 43.08 E-value: 1.82e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14194   173 GTPEFVAPEIVNYEPLGLEA-DMWSIGVITYILLSGASPF 211

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270798 [Multi-domain] Cd Length: 267 Bit Score: 43.29 E-value: 1.85e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHESFLDILNSL-SFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQgth 87
Cdd:cd06628    79 NHLNIFLEYVPGGSVATLLNNYgAFEEslVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNK-GGIKISDFGISK--- 154


                  ....*.
gi 1034562195  88 dtKIEL 93
Cdd:cd06628   155 --KLEA 158

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270786 [Multi-domain] Cd Length: 274 Bit Score: 43.00 E-value: 1.86e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkya 76
Cdd:cd06609    62 TKYygSFLKGSKLWIIMEYCGGGSVLDLLKPGPLDEtyIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEgdVK--- 138

                          90       100
                  ....*....|....*....|.
gi 1034562195  77 LVDFGLAQGTHDTKIELLKFV 97
Cdd:cd06609   139 LADFGVSGQLTSTMSKRNTFV 159

bifunctional N(6)-L-threonylcarbamoyladenine synthase/serine/threonine protein kinase;

Pssm-ID: 236586 [Multi-domain] Cd Length: 535 Bit Score: 43.72 E-value: 1.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  14 VIAMPYLEHESFLDILNslsfqEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRrlKKYALVDFGLAQGTH---DTK 90
Cdd:PRK09605  412 TIVMEYIGGKDLKDVLE-----GNPELVRKVGEIVAKLHKAGIVHGDLTTSNFIVRD--DRLYLIDFGLGKYSDlieDKA 484


                  ....*....
gi 1034562195  91 IELLKFVQS 99
Cdd:PRK09605  485 VDLHVLKQS 493

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270983 [Multi-domain] Cd Length: 255 Bit Score: 43.01 E-value: 2.00e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14081   162 GSPHYACPEVIKGEKYDGRKADIWSCGVILYALLVGALPF 201

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270904 [Multi-domain] Cd Length: 253 Bit Score: 43.01 E-value: 2.05e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPFYKAS 301
Cdd:cd14002   161 GTPLYMAPELVQEQPYDHTA-DLWSLGCILYELFVGQPPFYTNS 203

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270950 [Multi-domain] Cd Length: 281 Bit Score: 42.94 E-value: 2.09e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  15 IAMPYLEHESFLDILNSLSFQEVRE--YMLNLFK----ALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGLAQGT 86
Cdd:cd14048    92 IQMQLCRKENLKDWMNRRCTMESRElfVCLNIFKqiasAVEYLHSKGLIHRDLKPSNVFFslDDVVK---VGDFGLVTAM 168

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270972 [Multi-domain] Cd Length: 262 Bit Score: 42.88 E-value: 2.13e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:cd14070   100 LEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDEN-DNIKLIDFGLS 150

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270835 [Multi-domain] Cd Length: 286 Bit Score: 43.14 E-value: 2.17e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07844   164 YRPPDVLLGSTEYSTSLDMWGVGCIFYEMATGRPLFPGSTDVEDQLHKIFRVLGT 218

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270860 [Multi-domain] Cd Length: 256 Bit Score: 42.80 E-value: 2.19e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195  34 FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSN-FLYNRRLKKyaLVDFGLAQ 84
Cdd:cd08221    98 FPEevVLWYLYQIVSAVSHIHKAGILHRDIKTLNiFLTKADLVK--LGDFGISK 149

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270783 [Multi-domain] Cd Length: 258 Bit Score: 42.89 E-value: 2.33e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195 257 AGTPGFRAPEVLtKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMT 312
Cdd:cd06606   162 RGTPYWMAPEVI-RGEGYGRAADIWSLGCTVIEMATGKPPWSELGNPVAALFKIGS 216

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173729 [Multi-domain] Cd Length: 283 Bit Score: 42.80 E-value: 2.40e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195  42 LNLFKALKRIH-QFGIVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:cd06617   110 VSIVKALEYLHsKLSVIHRDVKPSNVLINRN-GQVKLCDFGIS 151

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270993 [Multi-domain] Cd Length: 291 Bit Score: 43.01 E-value: 2.47e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195 259 TPGFRAPEVLTKcpnQ--TTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd14091   161 TANFVAPEVLKK---QgyDAACDIWSLGVLLYTMLAGYTPFASGPND 204

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270924 [Multi-domain] Cd Length: 242 Bit Score: 42.72 E-value: 2.48e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195 256 RAGTPGFRAPEVL-TKCPNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd14022   146 KHGCPAYVSPEILnTSGSYSGKAADVWSLGVMLYTMLVGRYPFH 189

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270914 [Multi-domain] Cd Length: 254 Bit Score: 42.73 E-value: 2.53e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  12 HVVIAMPYLEH---ESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL-------YNRRLKKYALV 78
Cdd:cd14012    78 KVYLLTEYAPGgslSELLDSVGSVPLDTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLldrdagtGIVKLTDYSLG 154

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270692 [Multi-domain] Cd Length: 254 Bit Score: 42.58 E-value: 2.58e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 244 SICLSRRQQVAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKaSDDLTALAQIMTI 313
Cdd:cd05122   145 SAQLSDGKTRNTFVGTPYWMAPEVIQGKP-YGFKADIWSLGITAIEMAEGKPPYSE-LPPMKALFLIATN 212

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270858 [Multi-domain] Cd Length: 256 Bit Score: 42.49 E-value: 2.58e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNS---LSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSN-FLYNRRLKKyaLVDF 80
Cdd:cd08218    68 FEENGNLYIVMDYCDGGDLYKRINAqrgVLFPEdqILDWFVQLCLALKHVHDRKILHRDIKSQNiFLTKDGIIK--LGDF 145

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1034562195  81 GLAQGTHDTkIELLK-------FVQSEAQQERCSQNKSHI 113
Cdd:cd08218   146 GIARVLNST-VELARtcigtpyYLSPEICENKPYNNKSDI 184

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270989 [Multi-domain] Cd Length: 259 Bit Score: 42.52 E-value: 2.64e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKKYALVDFGLAQGTHDTKIELLK 95
Cdd:cd14087    93 SFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLYyhPGPDSKIMITDFGLASTRKKGPNCLMK 159

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270787 [Multi-domain] Cd Length: 267 Bit Score: 42.73 E-value: 2.66e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YC-FRKNDHVVIAMPYLEHESFLDILNSL----SFQEV------REymlnLFKALKRIHQFGIVHRDVKPSNFLYNRRlK 73
Cdd:cd06610    65 YTsFVVGDELWLVMPLLSGGSLLDIMKSSyprgGLDEAiiatvlKE----VLKGLEYLHSNGQIHRDVKAGNILLGED-G 139

                          90       100
                  ....*....|....*....|....*...
gi 1034562195  74 KYALVDFG----LAQGTHDTKIELLKFV 97
Cdd:cd06610   140 SVKIADFGvsasLATGGDRTRKVRKTFV 167

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271093 [Multi-domain] Cd Length: 259 Bit Score: 42.68 E-value: 2.72e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195 241 KVCSICLSRRQQVAPRA----GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLT 305
Cdd:cd14191   142 KLIDFGLARRLENAGSLkvlfGTPEFVAPEVINYEP-IGYATDMWSIGVICYILVSGLSPFMGDNDNET 209

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271131 [Multi-domain] Cd Length: 330 Bit Score: 42.71 E-value: 2.77e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEhESFLDIL-----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY---NRRLKKYAL 77
Cdd:cd14229    69 CFQHRNHTCLVFEMLE-QNLYDFLkqnkfSPLPLKVIRPILQQVATALKKLKSLGLIHADLKPENIMLvdpVRQPYRVKV 147

                          90       100
                  ....*....|....*....|..
gi 1034562195  78 VDFGLAqgTHDTKIELLKFVQS 99
Cdd:cd14229   148 IDFGSA--SHVSKTVCSTYLQS 167

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270985 [Multi-domain] Cd Length: 259 Bit Score: 42.36 E-value: 2.82e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195  47 ALKRIHQFGIVHRDVKPSNFLYNRRLK--KYALVDFGLAQ 84
Cdd:cd14083   113 AVDYLHSLGIVHRDLKPENLLYYSPDEdsKIMISDFGLSK 152

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271021 [Multi-domain] Cd Length: 255 Bit Score: 42.24 E-value: 2.86e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034562195 258 GTPGFRAPEVLTKCPN-QTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd14119   161 GSPAFQPPEIANGQDSfSGFKVDIWSAGVTLYNMTTGKYPFE 202

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271007 [Multi-domain] Cd Length: 269 Bit Score: 42.47 E-value: 2.91e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14105   173 GTPEFVAPEIVNYEPLGLEA-DMWSIGVITYILLSGASPF 211

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271132 [Multi-domain] Cd Length: 257 Bit Score: 42.45 E-value: 2.98e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASD 302
Cdd:cd14662   159 GTPAYIAPEVLSRKEYDGKVADVWSCGVTLYVMLVGAYPFEDPDD 203

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270844 [Multi-domain] Cd Length: 284 Bit Score: 42.49 E-value: 3.07e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  25 FLDILN--SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNrRLKKYALVDFGLAQ 84
Cdd:cd07860    88 FMDASAltGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLIN-TEGAIKLADFGLAR 148

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270983 [Multi-domain] Cd Length: 255 Bit Score: 42.24 E-value: 3.16e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  12 HVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLKkyaLVDFGLA 83
Cdd:cd14081    75 YLYLVLEYVSGGELFDYLVKkgrLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLldEKNNIK---IADFGMA 148

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271094 [Multi-domain] Cd Length: 261 Bit Score: 42.26 E-value: 3.18e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195 241 KVCSICLSRRQQvaPRA------GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLT 305
Cdd:cd14192   144 KIIDFGLARRYK--PREklkvnfGTPEFLAPEVVNY-DFVSFPTDMWSVGVITYMLLSGLSPFLGETDAET 211

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270849 [Multi-domain] Cd Length: 311 Bit Score: 42.69 E-value: 3.28e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07866   192 YRPPELLLGERRYTTAVDIWGIGCVFAEMFTRR-PILQGKSDIDQLHLIFKLCGT 245

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270837 [Multi-domain] Cd Length: 286 Bit Score: 42.36 E-value: 3.67e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHeSFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDF 80
Cdd:cd07847    69 FRRKRKLHLVFEYCDH-TVLNELeknpRGVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKqgQIK---LCDF 144


                  ....
gi 1034562195  81 GLAQ 84
Cdd:cd07847   145 GFAR 148

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271089 [Multi-domain] Cd Length: 265 Bit Score: 42.23 E-value: 3.69e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14187   169 GTPNYIAPEVLSK-KGHSFEVDIWSIGCIMYTLLVGKPPF 207

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270722 [Multi-domain] Cd Length: 318 Bit Score: 42.59 E-value: 3.71e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd05570   158 GTPDYIAPEILREQD-YGFSVDWWALGVLLYEMLAGQSPF 196

Catalytic domain of the Serine/Threonine protein kinases, Casein Kinase 1 delta and epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. The delta and epsilon isoforms of CK1 play important roles in circadian rhythm and cell growth. They phosphorylate PERIOD proteins (PER1-3), which are circadian clock proteins that fulfill negative regulatory functions. PER phosphorylation leads to its degradation. However, CRY proteins form a complex with PER and CK1delta/epsilon that protects PER from degradation and leads to nuclear accummulation of the complex, which inhibits BMAL1-CLOCK dependent transcription activation. CK1delta/epsilon also phosphorylate the tumor suppressor p53 and the cellular oncogene Mdm2, which are key regulators of cell growth, genome integrity, and the development of cancer. This subfamily also includes the CK1 fungal proteins Saccharomyces cerevisiae HRR25 and Schizosaccharomyces pombe HHP1. These fungal proteins are involved in DNA repair. The CK1 delta/epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271027 [Multi-domain] Cd Length: 275 Bit Score: 42.35 E-value: 3.72e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKYCFRKNDHVVIAM----PYLEhesflDILN----SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYN--RRL 72
Cdd:cd14125    61 VRWYGVEGDYNVMVMdllgPSLE-----DLFNfcsrKFSLKTVLMLADQMISRIEYVHSKNFIHRDIKPDNFLMGlgKKG 135

                          90
                  ....*....|....*...
gi 1034562195  73 KKYALVDFGLAQGTHDTK 90
Cdd:cd14125   136 NLVYIIDFGLAKKYRDPR 153

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143383 [Multi-domain] Cd Length: 343 Bit Score: 42.34 E-value: 3.85e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGS-------RETIQAAKTFGKSIlcsK 334
Cdd:cd07878   181 YRAPEIMLNWMHYNQTVDIWSVGCIMAELLKGK-ALFPGNDYIDQLKRIMEVVGTpspevlkKISSEHARKYIQSL---P 256

                          90
                  ....*....|
gi 1034562195 335 EVPAQDLRKL 344
Cdd:cd07878   257 HMPQQDLKKI 266

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270991 [Multi-domain] Cd Length: 263 Bit Score: 41.89 E-value: 3.96e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034562195 259 TPGFRAPEVL------TKCpnqttaiDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd14089   165 TPYYVAPEVLgpekydKSC-------DMWSLGVIMYILLCGYPPFY 203

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270976 [Multi-domain] Cd Length: 258 Bit Score: 42.01 E-value: 4.02e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA 83
Cdd:cd14074    98 NGLNEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFFEKQGLVKLTDFGFS 151

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271015 [Multi-domain] Cd Length: 263 Bit Score: 41.88 E-value: 4.13e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 253 VAPRAGTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPFYKASDDLTAL 307
Cdd:cd14113   162 IHQLLGSPEFAAPEIILGNPVSLTS-DLWSIGVLTYVLLSGVSPFLDESVEETCL 215

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270859 [Multi-domain] Cd Length: 256 Bit Score: 42.03 E-value: 4.16e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNS-----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFG 81
Cdd:cd08220    68 FLEDKALMIVMEYAPGGTLFEYIQQrkgslLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKRTVVKIGDFG 147


                  ...
gi 1034562195  82 LAQ 84
Cdd:cd08220   148 ISK 150

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173765 [Multi-domain] Cd Length: 257 Bit Score: 41.87 E-value: 4.21e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILN---SLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFG 81
Cdd:cd08225    68 FQENGRLFIVMEYCDGGDLMKRINrqrGVLFSEdqILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMVAKLGDFG 147

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1034562195  82 LAQGTHDTkIELLK-------FVQSEAQQERCSQNKSHI 113
Cdd:cd08225   148 IARQLNDS-MELAYtcvgtpyYLSPEICQNRPYNNKTDI 185

cyclin-dependent protein kinase; Provisional

Pssm-ID: 240233 [Multi-domain] Cd Length: 335 Bit Score: 42.44 E-value: 4.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   1 MGVKYCFRKNDHVVIAMPYLEHEsFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSN-FLYNRRLKKYA 76
Cdd:PTZ00024   83 MGLVDVYVEGDFINLVMDIMASD-LKKVVDRkirLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANiFINSKGICKIA 161


                  ....*..
gi 1034562195  77 lvDFGLA 83
Cdd:PTZ00024  162 --DFGLA 166

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270774 [Multi-domain] Cd Length: 409 Bit Score: 42.30 E-value: 4.38e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLKkyaLV 78
Cdd:cd05624   139 YAFQDENYLYLVMDYYVGGDLLTLLskfeDKLPEDMARFYIGEMVLAIHSIHQLHYVHRDIKPDNVLldMNGHIR---LA 215


                  ...
gi 1034562195  79 DFG 81
Cdd:cd05624   216 DFG 218

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270830 [Multi-domain] Cd Length: 294 Bit Score: 42.13 E-value: 4.85e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQ 84
Cdd:cd07837   104 NPLPAKTIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLVDKQKGLLKIADLGLGR 158

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132954 [Multi-domain] Cd Length: 264 Bit Score: 41.81 E-value: 4.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNSLSFqeVREYML-----NLFKALKRIHQF-GIVHRDVKPSNFLYNRR--LKkyaLV 78
Cdd:cd06623    68 FYKEGEISIVLEYMDGGSLADLLKKVGK--IPEPVLayiarQILKGLDYLHTKrHIIHRDIKPSNLLINSKgeVK---IA 142

                          90
                  ....*....|....*....
gi 1034562195  79 DFGLAQGTHDTKIELLKFV 97
Cdd:cd06623   143 DFGISKVLENTLDQCNTFV 161

Catalytic domain of the Serine/Threonine protein kinase, Fungal Casein Kinase 1 homolog 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. This subfamily is composed of fungal CK1 homolog 1 proteins, also called Yck1 in Saccharomyces cerevisiae and Cki1 in Schizosaccharomyces pombe. Yck1 (or Yck1p) and Cki1 are plasma membrane-anchored proteins. Yck1 phosphorylates and regulates Khd1p, a RNA-binding protein that represses translation of bud-localized mRNA. Cki1 phosphorylates and regulates phosphatidylinositol (PI)-(4)P-5-kinase, which catalyzes the last step in the sythesis of PI(4,5)P2, which is involved in actin cytoskeleton remodeling and membrane traffic. The fungal CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271029 [Multi-domain] Cd Length: 277 Bit Score: 41.71 E-value: 4.91e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195  51 IHQFGIVHRDVKPSNFLYNRRLKKYA----LVDFGLAQGTHDTK 90
Cdd:cd14127   112 IHEKNLIYRDIKPDNFLIGRPGTKNAnvihVVDFGMAKQYRDPK 155

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143368 [Multi-domain] Cd Length: 288 Bit Score: 41.87 E-value: 5.01e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd07863   105 LPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSG-GQVKLADFGLAR 156

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271104 [Multi-domain] Cd Length: 267 Bit Score: 41.53 E-value: 5.28e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  13 VVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY-----------NRRLKkyaLV 78
Cdd:cd14202    76 VYLVMEYCNGGDLADYLHTmrtLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLsysggrksnpnNIRIK---IA 152


                  ....*.
gi 1034562195  79 DFGLAQ 84
Cdd:cd14202   153 DFGFAR 158

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270830 [Multi-domain] Cd Length: 294 Bit Score: 41.74 E-value: 5.30e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSlLSGRYPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07837   176 YRAPEVLLGSTHYSTPVDMWSVGCIFAE-MSRKQPLFPGDSELQQLLHIFRLLGT 229

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270765 [Multi-domain] Cd Length: 332 Bit Score: 41.83 E-value: 5.44e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFykasddltalaqimTIRGSRETiQAAKTfgKSIL-CSKEV 336
Cdd:cd05614   168 GTIEYMAPEIIRGKSGHGKAVDWWSLGILMFELLTGASPF--------------TLEGEKNT-QSEVS--RRILkCDPPF 230

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1034562195 337 P------AQDL--RKLCERLRGMDSSTPKLTSDIQGH 365
Cdd:cd05614   231 PsfigpvARDLlqKLLCKDPKKRLGAGPQGAQEIKEH 267

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270749 [Multi-domain] Cd Length: 333 Bit Score: 41.92 E-value: 5.46e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05598   167 GTPNYIAPEVLLR-TGYTQLCDWWSVGVILYEMLVGQPPFL 206

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271003 [Multi-domain] Cd Length: 257 Bit Score: 41.76 E-value: 5.48e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  38 REYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTHDT 89
Cdd:cd14101   111 RRFFKQVVEAVQHCHSKGVVHRDIKDENILVDLRTGDIKLIDFGSGATLKDS 162

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270809 [Multi-domain] Cd Length: 277 Bit Score: 41.60 E-value: 5.57e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNS--LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd06641    71 YLKDTKLWIIMEYLGGGSALDLLEPgpLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEH-GEVKLADFGVAG 149

                          90
                  ....*....|...
gi 1034562195  85 GTHDTKIELLKFV 97
Cdd:cd06641   150 QLTDTQIKRN*FV 162

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270754 [Multi-domain] Cd Length: 321 Bit Score: 41.88 E-value: 5.73e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTaIDMWSAGVIFLSLLSGRYPFYkaSDDLTA-----LAQIMTIRGSRET 319
Cdd:cd05603   158 GTPEYLAPEVLRKEPYDRT-VDWWCLGAVLYEMLYGLPPFY--SRDVSQmydniLHKPLHLPGGKTV 221

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

Pssm-ID: 197581 [Multi-domain] Cd Length: 257 Bit Score: 41.36 E-value: 6.03e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195    8 RKNDHVVIAMPYLEHESFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLK-KYAlvDFGL 82
Cdd:smart00219  71 TEEEPLYIVMEYMEGGDLLSYLrknrPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVvKIS--DFGL 148


                   ....*....
gi 1034562195   83 AQGTHDTKI 91
Cdd:smart00219 149 SRDLYDDDY 157

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270954 [Multi-domain] Cd Length: 278 Bit Score: 41.64 E-value: 6.04e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHESFLDIL------NSLSF--------QEVREY-----MLNLFKALKRIHQFGIVHRDVKPSNFLYNRR 71
Cdd:cd14052    63 DNIVQLIDSWEYHGHLYIQtelcenGSLDVflselgllGRLDEFrvwkiLVELSLGLRFIHDHHFVHLDLKPANVLITFE 142

                          90
                  ....*....|....
gi 1034562195  72 --LKkyaLVDFGLA 83
Cdd:cd14052   143 gtLK---IGDFGMA 153

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270795 [Multi-domain] Cd Length: 260 Bit Score: 41.57 E-value: 6.05e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKky 75
Cdd:cd06625    65 VQYygCLQDEKSLSIFMEYMPGGSVKDEIKaygALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRdsNGNVK-- 142


                  ....*.
gi 1034562195  76 aLVDFG 81
Cdd:cd06625   143 -LGDFG 147

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270907 [Multi-domain] Cd Length: 255 Bit Score: 41.45 E-value: 6.18e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEH-ESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGT 86
Cdd:cd14005    79 DGFLLIMERPEPcQDLFDFITergALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLLINLRTGEVKLIDFGCGALL 158


                  ...
gi 1034562195  87 HDT 89
Cdd:cd14005   159 KDS 161

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270755 [Multi-domain] Cd Length: 326 Bit Score: 41.87 E-value: 6.43e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   1 MGVKYCFRKNDHVVIAMPYLEH-ESFLDILNSLSFQEVRE--YMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYAL 77
Cdd:cd05604    60 VGLHYSFQTTDKLYFVLDFVNGgELFFHLQRERSFPEPRArfYAAEIASALGYLHSINIVYRDLKPENILLDSQ-GHIVL 138


                  ....*..
gi 1034562195  78 VDFGLAQ 84
Cdd:cd05604   139 TDFGLCK 145

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271002 [Multi-domain] Cd Length: 254 Bit Score: 41.49 E-value: 6.45e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAM--PYLEHESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGL 82
Cdd:cd14100    74 FERPDSFVLVLerPEPVQDLFDFITERGALPEelARSFFRQVLEAVRHCHNCGVLHRDIKDENILIDLNTGELKLIDFGS 153


                  ....*..
gi 1034562195  83 AQGTHDT 89
Cdd:cd14100   154 GALLKDT 160

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271101 [Multi-domain] Cd Length: 286 Bit Score: 41.49 E-value: 6.49e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  11 DHVVIAMPYLEHESFLDI--LNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:cd14199   100 DHLYMVFELVKQGPVMEVptLKPLSEDQARFYFQDLIKGIEYLHYQKIIHRDVKPSNLLVGED-GHIKIADFGVS 173

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271097 [Multi-domain] Cd Length: 271 Bit Score: 41.53 E-value: 6.64e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14195   173 GTPEFVAPEIVNYEPLGLEA-DMWSIGVITYILLSGASPF 211

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271085 [Multi-domain] Cd Length: 268 Bit Score: 41.52 E-value: 6.83e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL---YNRRLKKYALVDFGLA 83
Cdd:cd14183    99 NKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLvyeHQDGSKSLKLGDFGLA 155

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterized by progressive incoordination, dysarthria and impairment of eye movements. Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients. The TTBK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271031 [Multi-domain] Cd Length: 262 Bit Score: 41.19 E-value: 6.86e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195  44 LFKALKRIHQFGIVHRDVKPSNFLYNR---RLKKYALVDFGLAQ 84
Cdd:cd14129   106 ILESIESIHSVGFLHRDIKPSNFAMGRfpsTCRKCYMLDFGLAR 149

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270848 [Multi-domain] Cd Length: 310 Bit Score: 41.59 E-value: 6.99e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034562195 256 RAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSgRYPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07865   183 RVVTLWYRPPELLLGERDYGPPIDMWGAGCIMAEMWT-RSPIMQGNTEQHQLTLISQLCGS 242

Catalytic domain of the Serine/Threonine Kinase, Kinase Interacting with Stathmin (also called U2AF homology motif (UHM) kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KIS (or UHMK1) contains an N-terminal kinase domain and a C-terminal domain with a UHM motif, a protein interaction motif initially found in the pre-mRNA splicing factor U2AF. It phosphorylates the splicing factor SF1, which enhances binding to the splice site to promote spliceosome assembly. KIS was first identified as a kinase that interacts with stathmin, a phosphoprotein that plays a role in axon development and microtubule dynamics. It localizes in RNA granules in neurons and is important in neurite outgrowth. The KIS/UHMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270922 [Multi-domain] Cd Length: 285 Bit Score: 41.46 E-value: 7.09e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  43 NLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA--QGTHDTK-IELLKFVQSEAQQERC 106
Cdd:cd14020   118 DVLEALAFLHHEGYVHADLKPRNILWSAEDECFKLIDFGLSfkEGNQDVKyIQTDGYRAPEAELQNC 184

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271128 [Multi-domain] Cd Length: 339 Bit Score: 41.54 E-value: 7.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRG--SRETI-QAAKTfgksilcskevpa 338
Cdd:cd14226   183 YRSPEVLLGLP-YDLAIDMWSLGCILVEMHTGE-PLFSGANEVDQMNKIVEVLGmpPVHMLdQAPKA------------- 247

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 339 qdlRKLCERLrGMDSSTPKLTSDIQghaSHQPAISEKTDHKASCLVQTPPGQYSGNSfkkgdsnscEHCFDEYntnlegw 418
Cdd:cd14226   248 ---RKFFEKL-PDGTYYLKKTKDGK---KYKPPGSRKLHEILGVETGGPGGRRAGEP---------GHTVEDY------- 304

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1034562195 419 nevpDEAYDLLDKLLDLNPASRITAEEALLHPFFKDM 455
Cdd:cd14226   305 ----LKFKDLILRMLDYDPKTRITPAEALQHSFFKRT 337

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270810 [Multi-domain] Cd Length: 277 Bit Score: 41.20 E-value: 7.16e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd06642    71 YLKGTKLWIIMEYLGGGSALDLLKPGPLEEtyIATILREILKGLDYLHSERKIHRDIKAANVLLSEQ-GDVKLADFGVAG 149

                          90
                  ....*....|...
gi 1034562195  85 GTHDTKIELLKFV 97
Cdd:cd06642   150 QLTDTQIKRNTFV 162

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270977 [Multi-domain] Cd Length: 255 Bit Score: 41.17 E-value: 7.29e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  15 IAMPYLEH-ESFLDILNS--LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGLAqgTHDT 89
Cdd:cd14075    78 LVMEYASGgELYTKISTEgkLSESEAKPLFAQIVSAVKHMHENNIIHRDLKAENVFYasNNCVK---VGDFGFS--THAK 152


                  ....*
gi 1034562195  90 KIELL 94
Cdd:cd14075   153 RGETL 157

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270802 [Multi-domain] Cd Length: 259 Bit Score: 41.23 E-value: 7.43e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   8 RKNDHVVIAMPYLEHESFLDILNSL-SFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGL 82
Cdd:cd06632    72 REEDNLYIFLEYVPGGSIHKLLQRYgAFEEpvIRLYTRQILSGLAYLHSRNTVHRDIKGANILVdtNGVVK---LADFGM 148


                  ..
gi 1034562195  83 AQ 84
Cdd:cd06632   149 AK 150

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270745 [Multi-domain] Cd Length: 348 Bit Score: 41.61 E-value: 7.50e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKAS-DDLTALAQIMTIRGSRETIQAAKTFGKSILcskev 336
Cdd:cd05593   177 GTPEYLAPEVLED-NDYGRAVDWWGLGVVMYEMMCGRLPFYNQDhEKLFELILMEDIKFPRTLSADAKSLLSGLL----- 250

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 337 paqdLRKLCERLRGmdssTPKLTSDIQGHA-----------------SHQPAISEKTDHK-------ASCLVQTPPGQYS 392
Cdd:cd05593   251 ----IKDPNKRLGG----GPDDAKEIMRHSfftgvnwqdvydkklvpPFKPQVTSETDTRyfdeeftAQTITITPPEKYD 322

                         170       180
                  ....*....|....*....|....*
gi 1034562195 393 GNSFKKGDSNSCEHcFDEYNTNLEG 417
Cdd:cd05593   323 EDGMDCMDNERRPH-FPQFSYSASG 346

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270734 [Multi-domain] Cd Length: 317 Bit Score: 41.23 E-value: 8.11e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034562195  27 DILNSLS----FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd05582    83 DLFTRLSkevmFTEedVKFYLAELALALDHLHSLGIIYRDLKPENILLDED-GHIKLTDFGLSK 145

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270845 [Multi-domain] Cd Length: 285 Bit Score: 41.25 E-value: 8.41e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGS 316
Cdd:cd07861   167 YRAPEVLLGSPRYSTPVDIWSIGTIFAEMATKK-PLFHGDSEIDQLFRIFRILGT 220

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270997 [Multi-domain] Cd Length: 258 Bit Score: 40.77 E-value: 8.93e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195 258 GTPGFRAPEVLtkcpNQT---TAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14095   161 GTPTYVAPEIL----AETgygLKVDIWAAGVITYILLCGFPPF 199

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270844 [Multi-domain] Cd Length: 284 Bit Score: 40.95 E-value: 9.36e-04

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd07860   166 YRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALF 201

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270763 [Multi-domain] Cd Length: 292 Bit Score: 40.88 E-value: 9.49e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  24 SFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQGTHD 88
Cdd:cd05612    90 SYLRNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKegHIK---LTDFGFAKKLRD 153

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271092 [Multi-domain] Cd Length: 261 Bit Score: 40.67 E-value: 9.72e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 241 KVCSICLSRR----QQVAPRAGTPGFRAPEVLTKcpNQTT-AIDMWSAGVIFLSLLSGRYPFYKASDDLT 305
Cdd:cd14190   144 KIIDFGLARRynprEKLKVNFGTPEFLSPEVVNY--DQVSfPTDMWSMGVITYMLLSGLSPFLGDDDTET 211

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270829 [Multi-domain] Cd Length: 283 Bit Score: 40.74 E-value: 1.03e-03

                          10        20
                  ....*....|....*....|....*.
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIF 287
Cdd:cd07835   165 YRAPEILLGSKHYSTPVDIWSVGCIF 190

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins (VRK1, VRK2, and VRK3) while invertebrates, specifically fruit flies and nematodes, seem to carry only a single ortholog. Mutations of VRK in Drosophila and Caenorhabditis elegans showed varying phenotypes ranging from embryonic lethality to mitotic and meiotic defects resulting in sterility. In vertebrates, VRK1 is implicated in cell cycle progression and proliferation, nuclear envelope assembly, and chromatin condensation. VRK2 is involved in modulating JNK signaling. VRK3 is an inactive pseudokinase that inhibits ERK signaling. The VRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270917 [Multi-domain] Cd Length: 300 Bit Score: 41.11 E-value: 1.04e-03

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1034562195  47 ALKRIHQFGIVHRDVKPSNFL--YNRRLKKYALVDFGLA 83
Cdd:cd14015   139 VLEYIHENGYVHADIKASNLLlgFGKNKDQVYLVDYGLA 177

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271017 [Multi-domain] Cd Length: 248 Bit Score: 40.71 E-value: 1.07e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTAL 307
Cdd:cd14115   153 GNPEFAAPEVIQGTP-VSLATDIWSIGVLTYVMLSGVSPFLDESKEETCI 201

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270912 [Multi-domain] Cd Length: 269 Bit Score: 40.74 E-value: 1.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 229 PASLTCDCYATDKVCSICLSRRQQVA---------------------PRAGTPGFRAPEVLTKCPNqTTAIDMWSAGVIF 287
Cdd:cd14010   122 PSNILLDGNGTLKLSDFGLARREGEIlkelfgqfsdegnvnkvskkqAKRGTPYYMAPELFQGGVH-SFASDLWALGCVL 200

                          90       100
                  ....*....|....*....|....*.
gi 1034562195 288 LSLLSGRYPFykASDDLTALA-QIMT 312
Cdd:cd14010   201 YEMFTGKPPF--VAESFTELVeKILN 224

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271077 [Multi-domain] Cd Length: 291 Bit Score: 40.78 E-value: 1.09e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKYCFRKNDHVVIAMPYLEHESFLD-ILNSLSFQEvREYMLNLF---KALKRIHQFGIVHRDVKPSNFLY---NRRLKKY 75
Cdd:cd14175    60 LKDVYDDGKHVYLVTELMRGGELLDkILRQKFFSE-REASSVLHticKTVEYLHSQGVVHRDLKPSNILYvdeSGNPESL 138


                  ....*....
gi 1034562195  76 ALVDFGLAQ 84
Cdd:cd14175   139 RICDFGFAK 147

putative serine/threonine kinase; Provisional

Pssm-ID: 165211 [Multi-domain] Cd Length: 294 Bit Score: 40.71 E-value: 1.12e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYaLVDFGLA 83
Cdd:PHA02882  128 IKNIMKDMLTTLEYIHEHGISHGDIKPENIMVDGNNRGY-IIDYGIA 173

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270758 [Multi-domain] Cd Length: 286 Bit Score: 40.66 E-value: 1.14e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195 235 DCYATDKVCSICLSRRQQVAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd05607   142 NCRLSDLGLAVEVKEGKPITQRAGTNGYMAPEILKEES-YSYPVDWFAMGCSIYEMVAGRTPF 203

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270730 [Multi-domain] Cd Length: 257 Bit Score: 40.70 E-value: 1.16e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  34 FQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRrlKKYA-LVDFGLA 83
Cdd:cd05578    97 FSEetVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDE--QGHVhITDFNIA 147

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270788 [Multi-domain] Cd Length: 259 Bit Score: 40.75 E-value: 1.16e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   3 VKY--CFRKNDHVVIAMPYLEHESFLDI---LNSLSFQEV----REYMlnlfKALKRIHQFGIVHRDVKPSNFLYNRR-- 71
Cdd:cd06613    60 VAYfgSYLRRDKLWIVMEYCGGGSLQDIyqvTGPLSELQIayvcRETL----KGLAYLHSTGKIHRDIKGANILLTEDgd 135

                          90
                  ....*....|....*..
gi 1034562195  72 LKkyaLVDFGL-AQGTH 87
Cdd:cd06613   136 VK---LADFGVsAQLTA 149

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271015 [Multi-domain] Cd Length: 263 Bit Score: 40.73 E-value: 1.16e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKK--YALVDFGLA 83
Cdd:cd14113    99 NLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVDQSLSKptIKLADFGDA 153

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270869 [Multi-domain] Cd Length: 256 Bit Score: 40.45 E-value: 1.17e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195  35 QEVREYMLNLFKALKRIHQFGIVHRDVKPSN-FLYNRRLKKyaLVDFGLA 83
Cdd:cd08530   103 DDIWRIFIQMLRGLKALHDQKILHRDLKSANiLLSAGDLVK--IGDLGIS 150

Catalytic domain of the Serine/Threonine protein kinases, Casein Kinase 1 alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1alpha plays a role in cell cycle progression, spindle dynamics, and chromosome segregation. It is also involved in regulating apoptosis mediated by Fas or the retinoid X receptor (RXR), and is a positive regulator of Wnt signaling. CK1alpha phosphorylates the NS5A protein of flaviviruses such as the Hepatitis C virus (HCV) and yellow fever virus (YFV), and influences flaviviral replication. The CK1 alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271030 [Multi-domain] Cd Length: 266 Bit Score: 40.57 E-value: 1.17e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195  48 LKRIHQFGIVHRDVKPSNFLY--NRRLKKYALVDFGLAQGTHDTK 90
Cdd:cd14128   109 IEYVHNKNFIHRDIKPDNFLMgiGRHCNKLFLIDFGLAKKYRDSR 153

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270723 [Multi-domain] Cd Length: 322 Bit Score: 40.80 E-value: 1.18e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05571   157 GTPEYLAPEVLED-NDYGRAVDWWGLGVVMYEMMCGRLPFY 196

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270755 [Multi-domain] Cd Length: 326 Bit Score: 40.72 E-value: 1.19e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTaIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05604   159 GTPEYLAPEVIRKQPYDNT-VDWWCLGSVLYEMLYGLPPFY 198

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271088 [Multi-domain] Cd Length: 256 Bit Score: 40.61 E-value: 1.21e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14186   164 GTPNYISPEIATRSAHGLES-DVWSLGCMFYTLLVGRPPF 202

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270748 [Multi-domain] Cd Length: 331 Bit Score: 40.79 E-value: 1.23e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLeheSFLDILNSLS-FQE------VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYAL 77
Cdd:cd05597    68 YAFQDENYLYLVMDYY---CGGDLLTLLSkFEDrlpeemARFYLAEMVLAIDSIHQLGYVHRDIKPDNVLLDRN-GHIRL 143


                  ....
gi 1034562195  78 VDFG 81
Cdd:cd05597   144 ADFG 147

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270790 [Multi-domain] Cd Length: 291 Bit Score: 40.81 E-value: 1.24e-03

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034562195  48 LKRIHQfgIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 83
Cdd:cd06616   125 LKEELK--IIHRDVKPSNILLDRNgnIK---LCDFGIS 157

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271009 [Multi-domain] Cd Length: 257 Bit Score: 40.64 E-value: 1.24e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  23 ESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRlKKYALVDFGLAQGTHDTKIELLKFV 97
Cdd:cd14107    83 EELLDRLflkGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILmvSPTR-EDIKICDFGFAQEITPSEHQFSKYG 161


                  ...
gi 1034562195  98 QSE 100
Cdd:cd14107   162 SPE 164

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271129 [Multi-domain] Cd Length: 355 Bit Score: 40.84 E-value: 1.28e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEhESFLDIL-----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY---NRRLKKYAL 77
Cdd:cd14227    84 CFQHKNHTCLVFEMLE-QNLYDFLkqnkfSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLvdpSRQPYRVKV 162

                          90       100
                  ....*....|....*....|..
gi 1034562195  78 VDFGLAqgTHDTKIELLKFVQS 99
Cdd:cd14227   163 IDFGSA--SHVSKAVCSTYLQS 182

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Genetic variations in TTBK1 are linked to Alzheimer's disease (AD). Hyperphosphorylated tau is a major component of paired helical filaments that accumulate in the brain of AD patients. Studies in transgenic mice show that TTBK1 is involved in the phosphorylation-dependent pathogenic aggregation of tau. The TTBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271032 [Multi-domain] Cd Length: 262 Bit Score: 40.40 E-value: 1.29e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  44 LFKALKRIHQFGIVHRDVKPSNFLYNR---RLKKYALVDFGLAQGTHDTKIEL 93
Cdd:cd14130   106 ILESIEAIHSVGFLHRDIKPSNFAMGRlpsTYRKCYMLDFGLARQYTNTTGEV 158

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270998 [Multi-domain] Cd Length: 295 Bit Score: 40.50 E-value: 1.31e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195  23 ESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR 70
Cdd:cd14096    92 EIFHQIVRLTYFSEdlSRHVITQVASAVKYLHEIGVVHRDIKPENLLFEP 141

mitogen-activated protein kinase kinase; Provisional

Pssm-ID: 215036 [Multi-domain] Cd Length: 353 Bit Score: 40.96 E-value: 1.32e-03

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034562195  51 IHQFGIVHRDVKPSNFLYNRRlKKYALVDFG----LAQ 84
Cdd:PLN00034  184 LHRRHIVHRDIKPSNLLINSA-KNVKIADFGvsriLAQ 220

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271020 [Multi-domain] Cd Length: 275 Bit Score: 40.42 E-value: 1.36e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  30 NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGLAQ 84
Cdd:cd14118   110 NPLSEETARSYFRDIVLGIEYLHYQKIIHRDIKPSNLLLgdDGHVK---IADFGVSN 163

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270753 [Multi-domain] Cd Length: 339 Bit Score: 40.77 E-value: 1.40e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   1 MGVKYCFRKNDHVVIAMPYLEH-ESFLDILNSLSFQEVRE--YMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYAL 77
Cdd:cd05602    71 VGLHFSFQTTDKLYFVLDYINGgELFYHLQRERCFLEPRArfYAAEIASALGYLHSLNIVYRDLKPENILLDSQ-GHIVL 149


                  ....*..
gi 1034562195  78 VDFGLAQ 84
Cdd:cd05602   150 TDFGLCK 156

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271004 [Multi-domain] Cd Length: 253 Bit Score: 40.32 E-value: 1.41e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  38 REYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTHDT 89
Cdd:cd14102   108 RGFFRQVLEAVRHCYSCGVVHRDIKDENLLVDLRTGELKLIDFGSGALLKDT 159

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271066 [Multi-domain] Cd Length: 256 Bit Score: 40.23 E-value: 1.43e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14164   163 GSRAYTPPEVILGTPYDPKKYDVWSLGVVLYVMVTGTMPF 202

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270978 [Multi-domain] Cd Length: 270 Bit Score: 40.16 E-value: 1.46e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPE-VLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14076   169 GSPCYAAPElVVSDSMYAGRKADIWSCGVILYAMLAGYLPF 209

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

Pssm-ID: 214568 [Multi-domain] Cd Length: 258 Bit Score: 40.22 E-value: 1.47e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195    8 RKNDHVVIAMPYLEHESFLDIL-----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLK-KYAlvDFG 81
Cdd:smart00221  71 TEEEPLMIVMEYMPGGDLLDYLrknrpKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVvKIS--DFG 148

                           90
                   ....*....|
gi 1034562195   82 LAQGTHDTKI 91
Cdd:smart00221 149 LSRDLYDDDY 158

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271114 [Multi-domain] Cd Length: 330 Bit Score: 40.70 E-value: 1.47e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRL-KKYALVDFGLA 83
Cdd:cd14212   100 LSLQLIRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLDsPEIKLIDFGSA 152

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271096 [Multi-domain] Cd Length: 269 Bit Score: 40.39 E-value: 1.48e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  25 FLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSN-FLYNRRLKK--YALVDFGLAQ 84
Cdd:cd14194    98 FLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENiMLLDRNVPKprIKIIDFGLAH 160

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271016 [Multi-domain] Cd Length: 259 Bit Score: 40.26 E-value: 1.48e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195 247 LSRRQQVAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLT 305
Cdd:cd14114   152 LDPKESVKVTTGTAEFAAPEIVEREP-VGFYTDMWAVGVLSYVLLSGLSPFAGENDDET 209

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270889 [Multi-domain] Cd Length: 259 Bit Score: 40.39 E-value: 1.51e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 235 DCYATdKVCSICLSRRQ--QVAPRAGTPGFRAPEVLTKCPNQT----TAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd13987   128 DCRRV-KLCDFGLTRRVgsTVKRVSGTIPYTAPEVCEAKKNEGfvvdPSIDVWAFGVLLFCCLTGNFPWEKADSD 201

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143374 [Multi-domain] Cd Length: 303 Bit Score: 40.45 E-value: 1.52e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQG 85
Cdd:cd07869   105 VKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDT-GELKLADFGLARA 152

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271111 [Multi-domain] Cd Length: 290 Bit Score: 40.46 E-value: 1.54e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYL---EHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVD 79
Cdd:cd14209    68 YSFKDNSNLYMVMEYVpggEMFSHLRRIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQgyIK---VTD 144


                  ....*
gi 1034562195  80 FGLAQ 84
Cdd:cd14209   145 FGFAK 149

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132946 [Multi-domain] Cd Length: 308 Bit Score: 40.50 E-value: 1.55e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034562195  48 LKRIHQfgIVHRDVKPSNFLYNRRlKKYALVDFGLAQGTHDT 89
Cdd:cd06615   115 LREKHK--IMHRDVKPSNILVNSR-GEIKLCDFGVSGQLIDS 153

probable serine/threonine protein kinase; Provisional

Pssm-ID: 178763 [Multi-domain] Cd Length: 507 Bit Score: 40.82 E-value: 1.60e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034562195  37 VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLA 83
Cdd:PLN03224  311 IKGVMRQVLTGLRKLHRIGIVHRDIKPENLLVTVD-GQVKIIDFGAA 356

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271089 [Multi-domain] Cd Length: 265 Bit Score: 40.30 E-value: 1.63e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDI---LNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLA 83
Cdd:cd14187    76 FEDNDFVYVVLELCRRRSLLELhkrRKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDM-EVKIGDFGLA 154


                  ....*....
gi 1034562195  84 qgthdTKIE 92
Cdd:cd14187   155 -----TKVE 158

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270762 [Multi-domain] Cd Length: 263 Bit Score: 40.16 E-value: 1.64e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195 229 PASLTCDCYATDKVCSICLSR----RQQVAPRAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd05611   125 PENLLIDQTGHLKLTDFGLSRngleKRHNKKFVGTPDYLAPETILGVG-DDKMSDWWSLGCVIFEFLFGYPPF 196

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271103 [Multi-domain] Cd Length: 271 Bit Score: 40.38 E-value: 1.65e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL--YNRRLK------KYALVD 79
Cdd:cd14201    78 NSVFLVMEYCNGGDLADYLQakgTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILlsYASRKKssvsgiRIKIAD 157


                  ....*...
gi 1034562195  80 FGLAQGTH 87
Cdd:cd14201   158 FGFARYLQ 165

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270738 [Multi-domain] Cd Length: 330 Bit Score: 40.25 E-value: 1.71e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   1 MGVKYCFRKNDHVVIAMPYLEH-ESFLDILNSLSFQEVRE--YMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYAL 77
Cdd:cd05586    59 VGLKFSFQTPTDLYLVTDYMSGgELFWHLQKEGRFSEDRAkfYIAELVLALEHLHKNDIVYRDLKPENILLDAN-GHIAL 137


                  ....*..
gi 1034562195  78 VDFGLAQ 84
Cdd:cd05586   138 CDFGLSK 144

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270787 [Multi-domain] Cd Length: 267 Bit Score: 40.03 E-value: 1.72e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195 257 AGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYK 299
Cdd:cd06610   167 VGTPCWMAPEVMEQVRGYDFKADIWSFGITAIELATGAAPYSK 209

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271085 [Multi-domain] Cd Length: 268 Bit Score: 39.98 E-value: 1.76e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCpNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTAL 307
Cdd:cd14183   167 GTPTYVAPEIIAET-GYGLKVDIWAAGVITYILLCGFPPFRGSGDDQEVL 215

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270992 [Multi-domain] Cd Length: 289 Bit Score: 40.09 E-value: 1.79e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1034562195  47 ALKRIHQFGIVHRDVKPSNFL--YNRRLKKYALVDFGLAQGTHDT 89
Cdd:cd14090   112 ALDFLHDKGIAHRDLKPENILceSMDKVSPVKICDFDLGSGIKLS 156

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270735 [Multi-domain] Cd Length: 268 Bit Score: 40.07 E-value: 1.83e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1034562195  36 EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd05583   100 EVRIYIGEIVLALEHLHKLGIIYRDIKLENILLDSE-GHVVLTDFGLSK 147

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270890 [Multi-domain] Cd Length: 316 Bit Score: 40.17 E-value: 1.87e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  12 HVVIAMPYLEHESFLDIL----NS--LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLynRRLKK-----YALVDF 80
Cdd:cd13988    67 HKVLVMELCPCGSLYTVLeepsNAygLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIM--RVIGEdgqsvYKLTDF 144


                  ....*...
gi 1034562195  81 GLAQGTHD 88
Cdd:cd13988   145 GAARELED 152

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270753 [Multi-domain] Cd Length: 339 Bit Score: 40.39 E-value: 1.92e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTaIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05602   170 GTPEYLAPEVLHKQPYDRT-VDWWCLGAVLYEMLYGLPPFY 209

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271082 [Multi-domain] Cd Length: 309 Bit Score: 40.24 E-value: 1.93e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  12 HVVIAMPYLEHESFLD-ILNSLSFQEVR--EYMLNLFKALKRIHQFGIVHRDVKPSNFLY-----NRRLKkyaLVDFGLA 83
Cdd:cd14180    75 HTYLVMELLRGGELLDrIKKKARFSESEasQLMRSLVSAVSFMHEAGVVHRDLKPENILYadesdGAVLK---VIDFGFA 151


                  .
gi 1034562195  84 Q 84
Cdd:cd14180   152 R 152

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271067 [Multi-domain] Cd Length: 263 Bit Score: 39.76 E-value: 1.93e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14165   168 GSAAYAAPEVLQGIPYDPRIYDIWSLGVILYIMVCGSMPY 207

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270926 [Multi-domain] Cd Length: 242 Bit Score: 39.86 E-value: 1.96e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195 256 RAGTPGFRAPEVL-TKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14024   146 KHGCPAYVGPEILsSRRSYSGKAADVWSLGVCLYTMLLGRYPF 188

cyclin-dependent kinase A; Provisional

Pssm-ID: 177649 [Multi-domain] Cd Length: 294 Bit Score: 40.19 E-value: 2.02e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGS 316
Cdd:PLN00009  169 YRAPEILLGSRHYSTPVDIWSVGCIFAEMVNQK-PLFPGDSEIDELFKIFRILGT 222

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132989 [Multi-domain] Cd Length: 292 Bit Score: 40.02 E-value: 2.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 217 NSAVMRKTASSCPASLTCDCYATDKVCSICLSRRQQVAPR---AGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSG 293
Cdd:cd06658   136 NQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRkslVGTPYWMAPEVISRLP-YGTEVDIWSLGIMVIEMIDG 214


                  ....*
gi 1034562195 294 RYPFY 298
Cdd:cd06658   215 EPPYF 219

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270796 [Multi-domain] Cd Length: 265 Bit Score: 39.98 E-value: 2.12e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195 243 CSICLSRRQQVAPRA------GTPGFRAPEVLTKcpNQTT----AIDMWSAGVIFLSLLSGRYPFYKASDDLtalaQIM 311
Cdd:cd06626   145 SAVKLKNNTTTMAPGevnslvGTPAYMAPEVITG--NKGEghgrAADIWSLGCVVLEMATGKRPWSELDNEW----AIM 217

Catalytic domain of the Protein Tyrosine Kinase, Wee1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Wee1 is a nuclear cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. There are two distinct Wee1 proteins in vertebrates showing different expression patterns, called Wee1a and Wee1b. They are functionally dstinct and are implicated in different steps of egg maturation and embryo development. The Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270953 [Multi-domain] Cd Length: 275 Bit Score: 39.69 E-value: 2.15e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195  10 NDHVVIAMPYLEHESFLDILNS-------LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSN 65
Cdd:cd14051    72 DDHMIIQNEYCNGGSLADAISEnekagerFSEAELKDLLLQVAQGLKYIHSQNLVHMDIKPGN 134

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270773 [Multi-domain] Cd Length: 409 Bit Score: 40.38 E-value: 2.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDIL----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDF 80
Cdd:cd05623   139 YAFQDDNNLYLVMDYYVGGDLLTLLskfeDRLPEDMARFYLAEMVLAIDSVHQLHYVHRDIKPDNILMDMN-GHIRLADF 217


                  .
gi 1034562195  81 G 81
Cdd:cd05623   218 G 218

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270981 [Multi-domain] Cd Length: 256 Bit Score: 39.56 E-value: 2.20e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14079   163 GSPNYAAPEVISGKLYAGPEVDVWSCGVILYALLCGSLPF 202

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270754 [Multi-domain] Cd Length: 321 Bit Score: 39.95 E-value: 2.22e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   1 MGVKYCFRKNDHVVIAMPYLEH-ESFLDILNSLSFQEVRE--YMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYAL 77
Cdd:cd05603    59 VGLHYSFQTSEKLYFVLDYVNGgELFFHLQRERCFLEPRArfYAAEVASAIGYLHSLNIIYRDLKPENILLDCQ-GHVVL 137


                  ....*..
gi 1034562195  78 VDFGLAQ 84
Cdd:cd05603   138 TDFGLCK 144

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.

Pssm-ID: 270870 [Multi-domain] Cd Length: 136 Bit Score: 38.19 E-value: 2.35e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd13968    87 ELDEKDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSED-GNVKLIDFG 136

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271000 [Multi-domain] Cd Length: 265 Bit Score: 39.77 E-value: 2.39e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195 258 GTPGFRAPEVL----TKCPNQ-TTAIDMWSAGVIFLSLLSGRYPFykasDDLTALAQIMTIRGSRETIQAAKTFGKS 329
Cdd:cd14098   164 GTMAYLAPEILmskeQNLQGGySNLVDMWSVGCLVYVMLTGALPF----DGSSQLPVEKRIRKGRYTQPPLVDFNIS 236

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270911 [Multi-domain] Cd Length: 251 Bit Score: 39.51 E-value: 2.41e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 258 GTPGFRAPEVLtKCPNQTTAIDMWSAGVIFLSLLSGRYPFyKASDDLTALAQIMT 312
Cdd:cd14009   156 GSPLYMAPEIL-QFQKYDAKADLWSVGAILFEMLVGKPPF-RGSNHVQLLRNIER 208

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271014 [Multi-domain] Cd Length: 259 Bit Score: 39.44 E-value: 2.43e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195 254 APRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd14112   157 VPVDGDTDWASPEFHNPETPITVQSDIWGLGVLTFCLLSGFHPFTSEYDD 206

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271014 [Multi-domain] Cd Length: 259 Bit Score: 39.44 E-value: 2.50e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195  27 DILNSLSF------QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY-NRRLKKYALVDFGLAQ 84
Cdd:cd14112    85 DVFTRFSSndyyseEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFqSVRSWQVKLVDFGRAQ 149

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270854 [Multi-domain] Cd Length: 297 Bit Score: 39.60 E-value: 2.53e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTIRGS--RETIQAaktfgksILCSKEVPAQ 339
Cdd:cd07873   166 YRPPDILLGSTDYSTQIDMWGVGCIFYEMSTGR-PLFPGSTVEEQLHFIFRILGTptEETWPG-------ILSNEEFKSY 237

                          90       100
                  ....*....|....*....|..
gi 1034562195 340 DLRKLceRLRGMDSSTPKLTSD 361
Cdd:cd07873   238 NYPKY--RADALHNHAPRLDSD 257

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270951 [Multi-domain] Cd Length: 284 Bit Score: 39.80 E-value: 2.53e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195  43 NLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA 83
Cdd:cd14049   128 QLLEGVTYIHSMGIVHRDLKPRNIFLHGSDIHVRIGDFGLA 168

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270723 [Multi-domain] Cd Length: 322 Bit Score: 39.65 E-value: 2.56e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   4 KYCFRKNDHVVIAMPYLEH-ESFLDILNSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLV 78
Cdd:cd05571    61 KYSFQTNDRLCFVMEYVNGgELFFHLSRERVFSEdrTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKdgHIK---IT 137


                  ....
gi 1034562195  79 DFGL 82
Cdd:cd05571   138 DFGL 141

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270724 [Multi-domain] Cd Length: 262 Bit Score: 39.52 E-value: 2.57e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEV-LTKcpNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd05572   154 GTPEYVAPEIiLNK--GYDFSVDYWSLGILLYELLTGRPPF 192

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271065 [Multi-domain] Cd Length: 257 Bit Score: 39.59 E-value: 2.62e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034562195 248 SRRQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14163   153 GGRELSQTFCGSTAYAAPEVLQGVPHDSRKGDIWSMGVVLYVMLCAQLPF 202

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271064 [Multi-domain] Cd Length: 259 Bit Score: 39.59 E-value: 2.66e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFykasDDlTALAQIMtirgsrETIQAAKTFGKSILCSKEV 336
Cdd:cd14162   166 GSYAYASPEILRGIPYDPFLSDIWSMGVVLYTMVYGRLPF----DD-SNLKVLL------KQVQRRVVFPKNPTVSEEC 233

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271009 [Multi-domain] Cd Length: 257 Bit Score: 39.49 E-value: 2.69e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034562195 241 KVCSICLSrrQQVAP------RAGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTAL 307
Cdd:cd14107   140 KICDFGFA--QEITPsehqfsKYGSPEFVAPEIVHQEP-VSAATDIWALGVIAYLSLTCHSPFAGENDRATLL 209

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270724 [Multi-domain] Cd Length: 262 Bit Score: 39.52 E-value: 2.71e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFG 81
Cdd:cd05572    62 FKDKKYLYMLMEYCLGGELWTILrdrGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNgyVK---LVDFG 138


                  ..
gi 1034562195  82 LA 83
Cdd:cd05572   139 FA 140

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271080 [Multi-domain] Cd Length: 293 Bit Score: 39.61 E-value: 2.86e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  13 VVIAMPYLEHESFLD-ILNSLSF--QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY---NRRLKKYALVDFGLAQ 84
Cdd:cd14178    72 VYLVMELMRGGELLDrILRQKCFseREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYmdeSGNPESIRICDFGFAK 149

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270765 [Multi-domain] Cd Length: 332 Bit Score: 39.52 E-value: 2.98e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1034562195  36 EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd05614   106 EVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSE-GHVVLTDFGLSK 153

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270737 [Multi-domain] Cd Length: 313 Bit Score: 39.09 E-value: 3.73e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  19 YLEHESFLDILNSlsfqevREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGLAQ 84
Cdd:cd05585    84 HLQREGRFDLSRA------RFYTAELLCALECLHKFNVIYRDLKPENILLDYT-GHIALCDFGLCK 142

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270736 [Multi-domain] Cd Length: 323 Bit Score: 39.31 E-value: 3.75e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034562195  40 YMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFGL 82
Cdd:cd05584   105 YLAEITLALGHLHSLGIIYRDLKPENILLDAQ-GHVKLTDFGL 146

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270742 [Multi-domain] Cd Length: 323 Bit Score: 39.12 E-value: 3.91e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFL-DILNSLSFQEVRE--YMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05590    63 CCFQTPDRLFFVMEFVNGGDLMfHIQKSRRFDEARArfYAAEITSALMFLHDKGIIYRDLKLDNVLLDHE-GHCKLADFG 141

                          90
                  ....*....|
gi 1034562195  82 LA-QGTHDTK 90
Cdd:cd05590   142 MCkEGIFNGK 151

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271070 [Multi-domain] Cd Length: 301 Bit Score: 39.26 E-value: 3.97e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   7 FRKNDHVVIAMPYLEHESFLDILNSLSF---QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKKYALVDFG 81
Cdd:cd14168    77 YESPNHLYLVMQLVSGGELFDRIVEKGFyteKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYfsQDEESKIMISDFG 156


                  ....*....
gi 1034562195  82 LA--QGTHD 88
Cdd:cd14168   157 LSkmEGKGD 165

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271035 [Multi-domain] Cd Length: 262 Bit Score: 38.79 E-value: 4.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEH--ESFL--DILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL---YNRRLKKyaLV 78
Cdd:cd14133    69 VFYFKNHLCIVFELLSQnlYEFLkqNKFQYLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILlasYSRCQIK--II 146

                          90       100
                  ....*....|....*....|.
gi 1034562195  79 DFGLAQGTHDTkieLLKFVQS 99
Cdd:cd14133   147 DFGSSCFLTQR---LYSYIQS 164

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173710 [Multi-domain] Cd Length: 316 Bit Score: 39.16 E-value: 4.40e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034562195 258 GTPGFRAPEVLTKCpNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd05620   158 GTPDYIAPEILQGL-KYTFSVDWWSFGVLLYEMLIGQSPFHGDDED 202

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271078 [Multi-domain] Cd Length: 339 Bit Score: 39.23 E-value: 4.42e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034562195  32 LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY---NRRLKKYALVDFGLAQ 84
Cdd:cd14176   110 FSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYvdeSGNPESIRICDFGFAK 165

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270764 [Multi-domain] Cd Length: 290 Bit Score: 38.83 E-value: 4.54e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIAMPYLEH-ESFLDILNSLSF--QEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYALVDFG 81
Cdd:cd05613    72 YAFQTDTKLHLILDYINGgELFTHLSQRERFteNEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSS-GHVVLTDFG 150


                  ...
gi 1034562195  82 LAQ 84
Cdd:cd05613   151 LSK 153

serine/threonine protein kinase; Provisional

Pssm-ID: 240344 [Multi-domain] Cd Length: 496 Bit Score: 39.47 E-value: 4.63e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPF 297
Cdd:PTZ00283  207 GTPYYVAPEIWRRKPYSKKA-DMFSLGVLLYELLTLKRPF 245

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271130 [Multi-domain] Cd Length: 355 Bit Score: 38.92 E-value: 4.83e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEhESFLDIL-----NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY---NRRLKKYAL 77
Cdd:cd14228    84 CFQHKNHTCLVFEMLE-QNLYDFLkqnkfSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLvdpVRQPYRVKV 162

                          90       100
                  ....*....|....*....|..
gi 1034562195  78 VDFGLAqgTHDTKIELLKFVQS 99
Cdd:cd14228   163 IDFGSA--SHVSKAVCSTYLQS 182

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271074 [Multi-domain] Cd Length: 267 Bit Score: 38.82 E-value: 4.93e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 259 TPGFRAPEVLTkcPNQ-TTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd14172   168 TPYYVAPEVLG--PEKyDKSCDMWSLGVIMYILLCGFPPFY 206

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143377 [Multi-domain] Cd Length: 309 Bit Score: 38.82 E-value: 5.40e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195 262 FRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGR--YPFYKASDDLTALAQIM 311
Cdd:cd07872   170 YRPPDVLLGSSEYSTQIDMWGVGCIFFEMASGRplFPGSTVEDELHLIFRLL 221

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270791 [Multi-domain] Cd Length: 295 Bit Score: 38.51 E-value: 5.50e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEheSFLDILNSLSFQEVREYML-----NLFKAL---KRIHqfGIVHRDVKPSNFLYNRR--LKky 75
Cdd:cd06618    82 YFITDSDVFICMELMS--TCLDKLLKRIQGPIPEDILgkmtvSIVKALhylKEKH--GVIHRDVKPSNILLDESgnVK-- 155


                  ....*...
gi 1034562195  76 aLVDFGLA 83
Cdd:cd06618   156 -LCDFGIS 162

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271091 [Multi-domain] Cd Length: 255 Bit Score: 38.37 E-value: 5.82e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPFYKAsdDLtalaqimtirgsRETIQAAKTFGKSILCSKEVP 337
Cdd:cd14189   163 GTPNYLAPEVLLRQGHGPES-DVWSLGCVMYTLLCGNPPFETL--DL------------KETYRCIKQVKYTLPASLSLP 227

                          90
                  ....*....|....*..
gi 1034562195 338 AQDL------RKLCERL 348
Cdd:cd14189   228 ARHLlagilkRNPGDRL 244

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271010 [Multi-domain] Cd Length: 255 Bit Score: 38.34 E-value: 5.92e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195 258 GTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTalaqIMTIR 314
Cdd:cd14108   160 GTPEFVAPEIVNQSP-VSKVTDIWPVGVIAYLCLTGISPFVGENDRTT----LMNIR 211

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270726 [Multi-domain] Cd Length: 316 Bit Score: 38.76 E-value: 6.06e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195   5 YCFRKNDHVVIAMPYLEHESFLDILNS-----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFL 67
Cdd:cd05574    68 ASFQTSTHLCFVMDYCPGGELFRLLQKqpgkrLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENIL 135

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271054 [Multi-domain] Cd Length: 279 Bit Score: 38.41 E-value: 6.29e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034562195  31 SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRrlKKYALVDFGL 82
Cdd:cd14152    93 SLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDN--GKVVITDFGL 142

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270869 [Multi-domain] Cd Length: 256 Bit Score: 38.14 E-value: 6.32e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAiDMWSAGVIFLSLLSGRYPF 297
Cdd:cd08530   163 GTPLYAAPEVWKGRPYDYKS-DIWSLGCLLYEMATFRPPF 201

serine/threonine-protein kinase PknD;

Pssm-ID: 183880 [Multi-domain] Cd Length: 932 Bit Score: 38.98 E-value: 6.65e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  11 DHVVIAMPYLEHESFLDILNS----------LSFQEVREYMLNLF----KALKRIHQFGIVHRDVKPSNFLynrrLKKYA 76
Cdd:PRK13184   75 DPVYYTMPYIEGYTLKSLLKSvwqkeslskeLAEKTSVGAFLSIFhkicATIEYVHSKGVLHRDLKPDNIL----LGLFG 150

                          90
                  ....*....|
gi 1034562195  77 ---LVDFGLA 83
Cdd:PRK13184  151 evvILDWGAA 160

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271006 [Multi-domain] Cd Length: 277 Bit Score: 38.30 E-value: 6.74e-03

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1034562195 259 TPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14104   161 SAEFYAPEVHQH-ESVSTATDMWSLGCLVYVLLSGINPF 198

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270775 [Multi-domain] Cd Length: 382 Bit Score: 38.49 E-value: 6.98e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195 258 GTPGFRAPEVLTKCpNQTTAIDMWSAGVIFLSLLSGRYPFYKAS 301
Cdd:cd05625   210 GTPNYIAPEVLLRT-GYTQLCDWWSVGVILFEMLVGQPPFLAQT 252

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270861 [Multi-domain] Cd Length: 260 Bit Score: 38.17 E-value: 7.38e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195  35 QEVREYMLNLFKALKRIHQFGIVHRDVKPSN-FLYNRRLKkyaLVDFGLAQ---GTHD 88
Cdd:cd08222   106 NQILDWFIQLLLAVQYMHERRILHRDLKAKNiFLKNNVIK---VGDFGISRilmGTSD 160

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270968 [Multi-domain] Cd Length: 272 Bit Score: 38.02 E-value: 7.42e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   5 YCFRKNDHVVIaMPYLEHESFLDILNS------LSFQEVREYMLNLFKALKRIHQFG---IVHRDVKPSNFLYNRRLKky 75
Cdd:cd14066    58 YCLESDEKLLV-YEYMPNGSLEDRLHChkgsppLPWPQRLKIAKGIARGLEYLHEECpppIIHGDIKSSNILLDEDFE-- 134


                  ....*....
gi 1034562195  76 ALV-DFGLA 83
Cdd:cd14066   135 PKLtDFGLA 143

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270789 [Multi-domain] Cd Length: 255 Bit Score: 37.96 E-value: 7.66e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGrYPFYKASDDLTALAQIMT 312
Cdd:cd06614   159 GTPYWMAPEVIKR-KDYGPKVDIWSLGIMCIEMAEG-EPPYLEEPPLRALFLITT 211

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270737 [Multi-domain] Cd Length: 313 Bit Score: 38.32 E-value: 7.97e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195 242 VCSICLSRRQQVAPRAGTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05585   140 LCKLNMKDDDKTNTFCGTPEYLAPELLLG-HGYTKAVDWWTLGVLLYEMLTGLPPFY 195

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270999 [Multi-domain] Cd Length: 266 Bit Score: 37.91 E-value: 8.05e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034562195 258 GTPGFRAPEVLTKcPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD 303
Cdd:cd14097   170 GTPIYMAPEVISA-HGYSQQCDIWSIGVIMYMLLCGEPPFVAKSEE 214

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270974 [Multi-domain] Cd Length: 253 Bit Score: 37.88 E-value: 8.09e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPF 297
Cdd:cd14072   160 GSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPF 199

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270909 [Multi-domain] Cd Length: 253 Bit Score: 37.84 E-value: 8.19e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034562195 248 SRRQQVApraGTPGFRAPEVLTKCPnQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLT 305
Cdd:cd14007   153 NRRKTFC---GTLDYLPPEMVEGKE-YDYKVDIWSLGVLCYELLVGKPPFESKSHQET 206

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270815 [Multi-domain] Cd Length: 261 Bit Score: 37.81 E-value: 8.51e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195  10 NDHVVIAMPYLEHESFLDILNSLSFQE-----VREYMLnlfKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGL 82
Cdd:cd06648    76 GDELWVVMEFLEGGALTDIVTHTRMNEeqiatVCRAVL---KALSFLHSQGVIHRDIKSDSILLTSdgRVK---LSDFGF 149


                  ....*...
gi 1034562195  83 -AQGTHDT 89
Cdd:cd06648   150 cAQVSKEV 157

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270727 [Multi-domain] Cd Length: 323 Bit Score: 38.07 E-value: 8.82e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034562195 258 GTPGFRAPEVLTKCPNQTTaIDMWSAGVIFLSLLSGRYPFY 298
Cdd:cd05575   158 GTPEYLAPEVLRKQPYDRT-VDWWCLGAVLYEMLYGLPPFY 197

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1 gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1gamma proteins are unique within the CK1 subfamily in that they are palmitoylated at the C-termini and are anchored to the plasma membrane. CK1gamma is involved in transducing the signaling of LDL-receptor-related protein 6 (LRP6) through direct phosphorylation following Wnt stimulation, resulting in the recruitment of the scaffold protein Axin. In Xenopus embryos, CK1gamma is required during anterio-posterior patterning. In higher vertebrates, three CK1gamma (gamma1-3) isoforms exist. In mammalian cells, CK1gamma2 has been implicated in regulating the synthesis of sphingomyelin, a phospholipid that is found in the outer leaflet of the plasma membrane, by hyperphosphorylating and inactivating the ceramide transfer protein CERT. CK1gamma2 also phosphorylates the transcription factor Smad-3 resulting in its ubiquitination and degradation. It inhibits Smad-3 mediated responses of Transforming Growth Factor-beta (TGF-beta) including cell growth arrest. The CK1 gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271028 [Multi-domain] Cd Length: 288 Bit Score: 37.79 E-value: 9.59e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034562195  23 ESFLDILN-SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYA----LVDFGLAQ 84
Cdd:cd14126    83 EDLFDLCDrTFSLKTVLMIAIQLISRIEYVHSKHLIYRDVKPENFLIGRQSTKKQhvihIIDFGLAK 149

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271022 [Multi-domain] Cd Length: 256 Bit Score: 37.73 E-value: 9.69e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034562195 258 GTPGFRAPEVLTkCPNQTTAIDMWSAGVIFLSLLSGRYPFYKAS 301
Cdd:cd14120   162 GSPMYMAPEVIM-SLQYDAKADLWSIGTIVYQCLTGKAPFQAQT 204

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271113 [Multi-domain] Cd Length: 329 Bit Score: 37.81 E-value: 9.72e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVVIAMPYLEHESFlDILNSLSFQ-----EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY---NRRLKKYAL 77
Cdd:cd14211    68 CFQHKNHTCLVFEMLEQNLY-DFLKQNKFSplplkYIRPILQQVLTALLKLKSLGLIHADLKPENIMLvdpVRQPYRVKV 146

                          90       100
                  ....*....|....*....|..
gi 1034562195  78 VDFGLAqgTHDTKIELLKFVQS 99
Cdd:cd14211   147 IDFGSA--SHVSKAVCSTYLQS 166

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270785 [Multi-domain] Cd Length: 275 Bit Score: 37.67 E-value: 9.86e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034562195   6 CFRKNDHVV------IAMPYLEHESFLDILNSL--SFQEVREYMLNLF-----KALKRIHQFGIVHRDVKPSNFLYNR-- 70
Cdd:cd06608    71 AFIKKDPPGgddqlwLVMEYCGGGSVTDLVKGLrkKGKRLKEEWIAYIlretlRGLAYLHENKVIHRDIKGQNILLTEea 150

                          90
                  ....*....|....*...
gi 1034562195  71 RLKkyaLVDFGL-AQGTH 87
Cdd:cd06608   151 EVK---LVDFGVsAQLDS 165