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]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715    38 LVKQGAEARVFRGRFQGRAAVIKHRFPKGYRHPALEARLGRRRTVQEARALLRCRRAGISAPVVFFVDYASNCLYMEEIE 117
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715   118 GsVTVRDYIQStmetektpqGLSNLAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPleqlNIVLIDFGLSFISALPEDKG 197
Cdd:TIGR03724  81 G-KPLKDVIEE---------NGDELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 41327715   198 VDLYVLEKAFLSTHPNT-ETVFEAFLKSYSTSSKKARPVLKKLDEVRLRGR 247
Cdd:TIGR03724 147 VDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

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]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715    38 LVKQGAEARVFRGRFQGRAAVIKHRFPKGYRHPALEARLGRRRTVQEARALLRCRRAGISAPVVFFVDYASNCLYMEEIE 117
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715   118 GsVTVRDYIQStmetektpqGLSNLAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPleqlNIVLIDFGLSFISALPEDKG 197
Cdd:TIGR03724  81 G-KPLKDVIEE---------NGDELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 41327715   198 VDLYVLEKAFLSTHPNT-ETVFEAFLKSYSTSSKKARPVLKKLDEVRLRGR 247
Cdd:TIGR03724 147 VDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  79 RRTVQEARALLRCRRAGISAPVVFFVDYASNCLYMEEIEGsVTVRDYIQSTMETEKtpqglsnLAKTIGQVLARMHDEDL 158
Cdd:COG3642   1 ERTRREARLLRELREAGVPVPKVLDVDPDDADLVMEYIEG-ETLADLLEEGELPPE-------LLRELGRLLARLHRAGI 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715 159 IHGDLTTSNMLLKPPleqlNIVLIDFGLSFISALPEDKGVDLYVLEKAFLSTHPN-TETVFEAFLKSYStSSKKARPVLK 237
Cdd:COG3642  73 VHGDLTTSNILVDDG----GVYLIDFGLARYSDPLEDKAVDLAVLKRSLESTHPDpAEELWEAFLEGYR-EVGPAEEVLR 147

                       170
                ....*....|
gi 41327715 238 KLDEVRLRGR 247
Cdd:COG3642 148 RLREIELRGR 157

Lipopolysaccharide kinase (Kdo/WaaP) family; These lipopolysaccharide kinases are related to protein kinases pfam00069. This family includes waaP (rfaP) gene product is required for the addition of phosphate to O-4 of the first heptose residue of the lipopolysaccharide (LPS) inner core region. It has previously been shown that WaaP is necessary for resistance to hydrophobic and polycationic antimicrobials in E. coli and that it is required for virulence in invasive strains of S. enterica.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715    39 VKQGAEARVFRGRFQGRaaVIKHRFPKGYRHPalearLGRRRTVQEARALLRCRRAGISAP-VVFFVDYASNCLY----- 112
Cdd:pfam06293  22 VVARVGNGVLRKYYRGG--MWGHLNRDLYRYP-----LGRTRAFREFRLIRRLREAGLPVPkPVAAGEVKVGGGYradll 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715   113 MEEIEGSVTVRDYIQSTME-TEKTPQGLsnlAKTIGQVLARMHDEDLIHGDLTTSNMLLKPP-LEQLNIVLIDFGLSFIS 190
Cdd:pfam06293  95 TERLEGAQSLADWLADWAVpSGELRRAI---WEAVGRLIRQMHRAGVQHGDLYAHHILLQQEgDEGFEAWLIDLDKGRLR 171

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 41327715   191 ALPE-DKGVDLYVLEKAFLsTHPNTETVFEAFLKSY 225
Cdd:pfam06293 172 LPARrWRNKDLARLLRSFL-NIGFTEADWERLLRAY 206

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]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715    38 LVKQGAEARVFRGRFQGRAAVIKHRFPKGYRHPALEARLGRRRTVQEARALLRCRRAGISAPVVFFVDYASNCLYMEEIE 117
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715   118 GsVTVRDYIQStmetektpqGLSNLAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPleqlNIVLIDFGLSFISALPEDKG 197
Cdd:TIGR03724  81 G-KPLKDVIEE---------NGDELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 41327715   198 VDLYVLEKAFLSTHPNT-ETVFEAFLKSYSTSSKKARPVLKKLDEVRLRGR 247
Cdd:TIGR03724 147 VDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

bifunctional N(6)-L-threonylcarbamoyladenine synthase/serine/threonine protein kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715   37 ELVKQGAEARVFRGRFQGRAAVIKHRFPKGYRHPALEARLGRRRTVQEARALLRCRRAGISAPVVFFVDYASNCLYMEEI 116
Cdd:PRK09605 339 HLIGKGAEADIKKGEYLGRDAVIKERVPKGYRHPELDERLRTERTRAEARLLSEARRAGVPTPVIYDVDPEEKTIVMEYI 418

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  117 EGsVTVRDYIQSTMEtektpqglsnLAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPleqlNIVLIDFGLSFISALPEDK 196
Cdd:PRK09605 419 GG-KDLKDVLEGNPE----------LVRKVGEIVAKLHKAGIVHGDLTTSNFIVRDD----RLYLIDFGLGKYSDLIEDK 483

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 41327715  197 GVDLYVLEKAFLSTHPNTETVFEAFLKSYSTsSKKARPVLKKLDEVRLRGR 247
Cdd:PRK09605 484 AVDLHVLKQSLESTHYDFEELWEAFLEGYRE-TEGAEDVLERLKEIEKRGR 533

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  41 QGAEARVFRGR--FQGRAAVIKhRFPKGYRHPALEARLgrrrtvQEARALLRCRRAGISAPVVFFVDYASNCLYMEEIEG 118
Cdd:cd00180   3 KGSFGKVYKARdkETGKKVAVK-VIPKEKLKKLLEELL------REIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEG 75

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 41327715 119 sVTVRDYIQSTMETEkTPQGLSNLAKTIGQVLARMHDEDLIHGDLTTSNMLLKpplEQLNIVLIDFGLSFISALPEDK 196
Cdd:cd00180  76 -GSLKDLLKENKGPL-SEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLD---SDGTVKLADFGLAKDLDSDDSL 148

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  40 KQGAEARVFRGRFQGRAAVIkhrfpkGYRHPALEARLGRRRTVQEARALLRCRRAGISAPvvFFVDYAS----NCLYMEE 115
Cdd:cd13968   2 GEGASAKVFWAEGECTTIGV------AVKIGDDVNNEEGEDLESEMDILRRLKGLELNIP--KVLVTEDvdgpNILLMEL 73

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715 116 IEGsVTVRDYIQSTMETEKTPQGLSNLaktIGQVLARMHDEDLIHGDLTTSNMLLKpplEQLNIVLIDFG 185
Cdd:cd13968  74 VKG-GTLIAYTQEEELDEKDVESIMYQ---LAECMRLLHSFHLIHRDLNNDNILLS---EDGNVKLIDFG 136

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  36 LELVKQGAEARVFRGRFQ--GRAAVIKhrFPkgyRHPALEARLGRRRTVQEARALLRCRRAGIsaPVVFFVDYASNCLY- 112
Cdd:cd14014   5 VRLLGRGGMGEVYRARDTllGRPVAIK--VL---RPELAEDEEFRERFLREARALARLSHPNI--VRVYDVGEDDGRPYi 77

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 41327715 113 -MEEIEGsVTVRDYIQstMETEKTPQGLSNLAKTIGQVLARMHDEDLIHGDLTTSNMLLkppLEQLNIVLIDFGLS 187
Cdd:cd14014  78 vMEYVEG-GSLADLLR--ERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILL---TEDGRVKLTDFGIA 147

Serine/threonine-protein kinase RIO1 [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  39 VKQGAEARVFRGRFQG---RAAvikhrfpKGYR------HPALEARLGRRR----------------TVQEARALLRCRR 93
Cdd:COG1718  54 LSTGKEANVFLARRPGgelVAA-------KIYRtatssfKRMAQYIEGDPRfmgkgsfgrrqlifawARKEFRNLYRLYE 126

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  94 AGISAP--VVFFvdyaSNCLYMEEI--EGSV--TVRDyiqstmeTEKTPQGLSNLAKTIGQVLARMHDEDLIHGDLTTSN 167
Cdd:COG1718 127 AGVRVPepIAFY----GNVLLMEFIgdDGVPapRLKD-------VELEPEEAEELYEQLIEYIVRLYKAGLVHGDLSEYN 195

                       170
                ....*....|....*...
gi 41327715 168 MLLKPPleqlNIVLIDFG 185
Cdd:COG1718 196 ILVDDG----GPVIIDLP 209

Predicted Ser/Thr protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  30 SRFLSGLELVKQGAEARVFRGRFQGRAAVIKHRFPKGYRHPALearlgrrrtvQEARALLRCRRAGIsAPVVFfvDYASN 109
Cdd:COG2112  39 GTLIGGLRLLGKGYRGVVFLGKLGGKKVALKIRRTDSPRPSLK----------KEAEILKKANGAGV-GPKLY--DYGRD 105

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715 110 CLYMEEIEGsVTVRDYIQSTmetektpqGLSNLAKTIGQVLA---RMHDEDLIHGDLT--TSNMLLKppleQLNIVLIDF 184
Cdd:COG2112 106 FLVMEYIEG-EPLKDWLENL--------DKEELRKVIRELLEaayLLDRIGIDHGELSrpGKHVIVD----KGRPYIIDF 172

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 41327715 140 SNLAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPLEQLNIVLIDFGLS 187
Cdd:cd05117 102 AKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDSPIKIIDFGLA 149

RIO1 family; This is a family of atypical serine kinases which are found in archaea, bacteria and eukaryotes. Activity of Rio1 is vital in Saccharomyces cerevisiae for the processing of ribosomal RNA, as well as for proper cell cycle progression and chromosome maintenance. The structure of RIO1 has been determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715    84 EARALLRCRRAGISAPVVffVDYASNCLYMEEIEG----SVTVRDyiqstMETEKTPQglsNLAKTIGQVLARMHDEDLI 159
Cdd:pfam01163  56 EFRNLKRLYEAGVPVPKP--IDVNRHVLVMEFIGKdgvpAPKLKD-----VELEEAEE---IYDEIIREMRRLYQEAGLV 125

                          90       100
                  ....*....|....*....|....*.
gi 41327715   160 HGDLTTSNMLLKPPleqlNIVLIDFG 185
Cdd:pfam01163 126 HGDLSEYNILVHDD----KPVIIDVP 147

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 41327715 111 LYMEEIEGSvTVRDYIQSTMETEKTPQGLSnLAKTIGQVLARMHDEDLIHGDLTTSNMLLKpplEQLNIVLIDFGLS 187
Cdd:cd14154  67 LITEYIPGG-TLKDVLKDMARPLPWAQRVR-FAKDIASGMAYLHSMNIIHRDLNSHNCLVR---EDKTVVVADFGLA 138

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715 133 EKTPQGLSN-----LAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPLEQlnIVLIDFGLS 187
Cdd:cd05118  92 KDYPRGLPLdliksYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQ--LKLADFGLA 149

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates 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. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  38 LVKQGAEARVFRGRFQGRAAVIKhrfpKGYRHPALEARLGRRRTVQEARALLRCRRAGISAPVVFFVDYASNCLYMEEIE 117
Cdd:cd14146   1 IIGVGGFGKVYRATWKGQEVAVK----AARQDPDEDIKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFAR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715 118 GSVTVRDYIQSTMETEKT------PQGLSNLAKTIGQVLARMHDE---DLIHGDLTTSNMLLKPPLEQLNIV-----LID 183
Cdd:cd14146  77 GGTLNRALAAANAAPGPRrarripPHILVNWAVQIARGMLYLHEEavvPILHRDLKSSNILLLEKIEHDDICnktlkITD 156

                ....
gi 41327715 184 FGLS 187
Cdd:cd14146 157 FGLA 160

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715 107 ASNCLYMEEIEGSVtvrdyiqSTMETEKTPQGLS-----NLAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPLEQLNivL 181
Cdd:cd14020  82 PSRCLLLELLDVSV-------SELLLRSSNQGCSmwmiqHCARDVLEALAFLHHEGYVHADLKPRNILWSAEDECFK--L 152

                ....*..
gi 41327715 182 IDFGLSF 188
Cdd:cd14020 153 IDFGLSF 159

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 41327715 141 NLAKTIGQVLARMHDEDLIHGDLTTSNMLLKPPLEQLNIVLIDFGLSF 188
Cdd:cd14015 131 QLALRILDVLEYIHENGYVHADIKASNLLLGFGKNKDQVYLVDYGLAS 178

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715  36 LELVKQGAEARVF--RGRFQGRAAVIKH-RFPKGYRHPALEarlgrrrtvQEARALLRCRRAGISAPVVFFVDYASNCLY 112
Cdd:cd14166   8 MEVLGSGAFSEVYlvKQRSTGKLYALKCiKKSPLSRDSSLE---------NEIAVLKRIKHENIVTLEDIYESTTHYYLV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715 113 MEEIEGSVTVRDYIQSTMETEKtpqglsNLAKTIGQVLAR---MHDEDLIHGDLTTSNMLLKPPLEQLNIVLIDFGLSFI 189
Cdd:cd14166  79 MQLVSGGELFDRILERGVYTEK------DASRVINQVLSAvkyLHENGIVHRDLKPENLLYLTPDENSKIMITDFGLSKM 152

                ....*....
gi 41327715 190 salpEDKGV 198
Cdd:cd14166 153 ----EQNGI 157

3-deoxy-D-manno-octulosonic-acid kinase; Reviewed

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715   75 RLGRRRTVQEARALLRCRRAGISAPVVFFVDYASNCLY------MEEIEGSVTVRDYIQSTMETEKTPQglsnlakTIGQ 148
Cdd:PRK01723  81 GLERTRAFAEFRLLAQLYEAGLPVPRPIAARVVRHGLFyradilIERIEGARDLVALLQEAPLSEEQWQ-------AIGQ 153

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 41327715  149 VLARMHDEDLIHGDLTTSNMLLKPpleQLNIVLIDF 184
Cdd:PRK01723 154 LIARFHDAGVYHADLNAHNILLDP---DGKFWLIDF 186

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 41327715 148 QVLAR---MHDEDLIHGDLTTSNMLLKPPLEQLNIVLIDFGLS 187
Cdd:cd14016 104 QMISRleyLHSKGYIHRDIKPENFLMGLGKNSNKVYLIDFGLA 146

RIO-like kinase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41327715     62 RFPKGYRHPALEARLGRRRtvqEARALLRCRRAGISAPVVffVDYASNCLYMEEIEG----SVTVRDYiqstmetEKTPQ 137
Cdd:smart00090  81 RFKYRKINPRKLVRLWAEK---EFRNLQRLYEAGVPVPKP--IAWRRNVLVMEFIGGdglpAPRLKDV-------EPEEE 148

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 41327715    138 GLSNLAKTIGQVLARMHDE-DLIHGDLTTSNMLLKPPleqlNIVLIDFGLS 187
Cdd:smart00090 149 EEFELYDDILEEMRKLYKEgELVHGDLSEYNILVHDG----KVVIIDVSQS 195

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.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 41327715 150 LARMHDEDLIHGDLTTSNMLLKpplEQLNIVLIDFGL 186
Cdd:cd14078 114 VAYVHSQGYAHRDLKPENLLLD---EDQNLKLIDFGL 147

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.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 41327715 153 MHDEDLIHGDLTTSNMLLKpplEQLNIVLIDFGLS 187
Cdd:cd14070 119 LHRAGVVHRDLKIENLLLD---ENDNIKLIDFGLS 150