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Conserved domains on  [gi|568930781|ref|XP_006538706|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [Mus musculus]

Protein Classification

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta( domain architecture ID 10490333)

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 705-1072 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


:

Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 813.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  705 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 784
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  785 KMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 864
Cdd:cd05174    80 KMKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  865 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 944
Cdd:cd05174   159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  945 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 1024
Cdd:cd05174   239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 568930781 1025 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 1072
Cdd:cd05174   319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 5.11e-92

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


:

Pssm-ID: 176075  Cd Length: 173  Bit Score: 291.14  E-value: 5.11e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  314 VSLWSLEQPFSIELIEGRKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCF 392
Cdd:cd08693     1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  393 ALYAVVEKAKKARSTK----KKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESA 468
Cdd:cd08693    81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                         170
                  ....*....|...
gi 568930781  469 AALVIYLPEVAPH 481
Cdd:cd08693   161 TALHISFPEYKPE 173
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-713 2.34e-78

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


:

Pssm-ID: 214537  Cd Length: 184  Bit Score: 254.49  E-value: 2.34e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAqvsreggsgrqprgrwtvpah 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVA--------------------- 62

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    584 pylttklsQMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLL 663
Cdd:smart00145   63 --------QALSLLLSWAPLDPEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLL 134

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|
gi 568930781    664 GRALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMK 713
Cdd:smart00145  135 ERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEAYLRGCGTHLKELLK 184
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 6.89e-36

PI3-kinase family, p85-binding domain;


:

Pssm-ID: 460483  Cd Length: 74  Bit Score: 130.33  E-value: 6.89e-36
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568930781    34 FPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 7.50e-32

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


:

Pssm-ID: 395642  Cd Length: 106  Bit Score: 120.09  E-value: 7.50e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   182 LLRVSNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVEQpeEYALQVNGRHEYLYGNYPLCHFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 568930781   262 ICSCLHSGLTPHLTMVHSSS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 705-1072 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 813.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  705 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 784
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  785 KMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 864
Cdd:cd05174    80 KMKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  865 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 944
Cdd:cd05174   159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  945 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 1024
Cdd:cd05174   239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 568930781 1025 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 1072
Cdd:cd05174   319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 5.11e-92

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 291.14  E-value: 5.11e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  314 VSLWSLEQPFSIELIEGRKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCF 392
Cdd:cd08693     1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  393 ALYAVVEKAKKARSTK----KKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESA 468
Cdd:cd08693    81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                         170
                  ....*....|...
gi 568930781  469 AALVIYLPEVAPH 481
Cdd:cd08693   161 TALHISFPEYKPE 173
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 806-1023 1.04e-80

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 263.00  E-value: 1.04e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    806 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 870
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    871 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 937
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    938 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 1017
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 568930781   1018 ELSCSK 1023
Cdd:smart00146  235 DWRSGK 240
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-713 2.34e-78

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 254.49  E-value: 2.34e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAqvsreggsgrqprgrwtvpah 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVA--------------------- 62

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    584 pylttklsQMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLL 663
Cdd:smart00145   63 --------QALSLLLSWAPLDPEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLL 134

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|
gi 568930781    664 GRALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMK 713
Cdd:smart00145  135 ERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEAYLRGCGTHLKELLK 184
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 804-1020 2.31e-76

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 251.09  E-value: 2.31e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   804 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAAF 880
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   881 N-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESG 935
Cdd:pfam00454   82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   936 QLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG 1015
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*
gi 568930781  1016 LPELS 1020
Cdd:pfam00454  236 LPDWS 240
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 505-704 2.87e-71

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 234.13  E-value: 2.87e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  505 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQvsreggsgrqprgrwtvpahp 584
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQ--------------------- 58

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  585 ylttklsqMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLG 664
Cdd:cd00872    59 --------MYQLLKRWPKLKPEQALELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLK 130

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 568930781  665 RALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGS 704
Cdd:cd00872   131 RALRNQRIGHFFFWHLRSEMHNPSVSQRFGLLLEAYLRGC 170
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 499-713 5.23e-57

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 194.86  E-value: 5.23e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   499 ERGRITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQVsreggsgrqprgrw 578
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAEA-------------- 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   579 tvpahpylttkLSQMLYllcsWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCEL 658
Cdd:pfam00613   66 -----------LSLLLK----WAPIDPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYL 130

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568930781   659 TKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMK 713
Cdd:pfam00613  131 SRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
709-1045 1.88e-36

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 150.32  E-value: 1.88e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  709 KVLMKQGE--ALSKLKALNDFVKVSSQKTTKPQTKEMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCSvEQCT 780
Cdd:COG5032  1698 KIRKKFKIdiSLLNLSRKLYISVLRSIRKRLKRLLELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEP-EVSV 1776

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  781 FMDSKMKPLWIMYSseeaGSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLI 855
Cdd:COG5032  1777 VKSHLQRPRRLTIR----GSDGKLySFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGII 1852

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  856 EVVLHSDTIANI------QLNKS-NMAATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTL 907
Cdd:COG5032  1853 EWVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFAR 1932

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  908 SCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERF 986
Cdd:COG5032  1933 SLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSF 2006

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568930781  987 RGYCERAYTILRRHGLLFLHLFALMRAAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 1045
Cdd:COG5032  2007 RELCETAFRALRKNADSLMNVLELFVRDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 6.89e-36

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 130.33  E-value: 6.89e-36
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568930781    34 FPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 7.50e-32

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 120.09  E-value: 7.50e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   182 LLRVSNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVEQpeEYALQVNGRHEYLYGNYPLCHFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 568930781   262 ICSCLHSGLTPHLTMVHSSS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 312-407 2.34e-30

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 115.52  E-value: 2.34e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    312 SSVSLWSLEQPFSIELIEGRKVNADERM-KLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARL 390
Cdd:smart00142    4 ESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARL 83

                            90
                    ....*....|....*..
gi 568930781    391 CFALYAVVEKAKKARST 407
Cdd:smart00142   84 CITIYAVKNPSKGSEFG 100
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 339-448 2.49e-22

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 93.97  E-value: 2.49e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   339 MKLVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarstkKKSKKADCP 417
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVP 71

                           90       100       110
                   ....*....|....*....|....*....|.
gi 568930781   418 IAWANLMLFDYKDQLKTGERCLYMWPSVPDE 448
Cdd:pfam00792   72 IGWVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 2.88e-21

PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.


Pssm-ID: 197539  Cd Length: 78  Bit Score: 88.69  E-value: 2.88e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568930781     31 YLNFPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 183-281 3.55e-16

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 75.44  E-value: 3.55e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    183 LRVSNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPlVEQPEEYALQVNGRHEYLYGNYPLCHFQYI 262
Cdd:smart00144   11 LKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQV-DPTSEDYILKVCGRDEYLLGDHPLGSFEYI 89

                            90
                    ....*....|....*....
gi 568930781    263 CSCLHSGLTPHLTMVHSSS 281
Cdd:smart00144   90 RNCLKNGTEPHLVLMTLSA 108
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 705-1072 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 813.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  705 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 784
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  785 KMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 864
Cdd:cd05174    80 KMKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  865 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 944
Cdd:cd05174   159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  945 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 1024
Cdd:cd05174   239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 568930781 1025 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 1072
Cdd:cd05174   319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 708-1070 0e+00

Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. In vitro, they can also phosphorylate the substrates PtdIns and PtdIns(4)P. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270709 [Multi-domain]  Cd Length: 363  Bit Score: 656.24  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  708 MKVLMKQGEALSKLKALNDFVKVssQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDSKMK 787
Cdd:cd05165     1 LKSLSRQVEALNKLKKLSDILKE--KKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELI-IEKCKVMDSKKR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  788 PLWIMYSSEE--AGSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 865
Cdd:cd05165    78 PLWLVFENADplALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIA 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  866 NIQLNKSNMAaTAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 944
Cdd:cd05165   158 NIQKKKGKVA-TLAFNKDSLHKWLKEKNKtGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGH 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  945 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTN-NSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSK 1023
Cdd:cd05165   237 FLGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVK 316

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 568930781 1024 DIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 1070
Cdd:cd05165   317 DIEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 708-1071 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kbeta can be activated by G-protein-coupled receptors. Deletion of PI3Kbeta in mice results in early lethality at around day three of development. PI3Kbeta plays an important role in regulating sustained integrin activation and stable platelet agrregation, especially under conditions of high shear stress. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270717 [Multi-domain]  Cd Length: 362  Bit Score: 622.75  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  708 MKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKMK 787
Cdd:cd05173     1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSEL-NVEKCKYMDSKMK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  788 PLWIMYSSEEAGSaGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 867
Cdd:cd05173    80 PLWIVYNNKLFGG-DSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  868 QLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLG 947
Cdd:cd05173   159 QLNSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILG 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  948 NFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQY 1027
Cdd:cd05173   239 NFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQY 318

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....
gi 568930781 1028 LKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 1071
Cdd:cd05173   319 LKDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 708-1054 1.38e-149

Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class II PI3Ks comprise three catalytic isoforms that do not associate with any regulatory subunits. They selectively use PtdIns as a susbtrate to produce PtsIns(3)P. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270624 [Multi-domain]  Cd Length: 334  Bit Score: 449.33  E-value: 1.38e-149
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  708 MKVLMKQGEALSKLKALNDFVK-VSSQKttkpqtkemmhmcmRQETYMEALSHLQS------PLDPSTlleEVCS--VEQ 778
Cdd:cd00891     1 REELLKQVKVLDELKEIAKKIKeEPSEE--------------RKEVLEKLLQKLELpkkftlPLDPRM---EVKGliVEK 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  779 CTFMDSKMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVV 858
Cdd:cd00891    64 CKVMDSKKLPLWLVFKNADPG-GDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVV 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  859 LHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 937
Cdd:cd00891   143 PNSETTAAIQ--KKYGGFGAAFKDTPISNWLKKHNPTEEeYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHL 220

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  938 FHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 1017
Cdd:cd00891   221 FHIDFGHFLGNFKKKFGIKRERAPFVFTPEMAYVM-GGE--DSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIP 297

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 568930781 1018 ELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALR 1054
Cdd:cd00891   298 ELQSIEDIEYLRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 711-1068 2.96e-117

Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. They are activated by a variety of stimuli including chemokines, cytokines, lysophosphatidic acid (LPA), insulin, and tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 365.46  E-value: 2.96e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  711 LMKQGEALSKLKALNDFVKvssqkttkpQTKEmmhmCMRQETYMEALSHLQS---------PLDPSTLLEEVcSVEQCTF 781
Cdd:cd05166     4 FLKQHVLVQALTSIAEKVK---------SAKD----SARENALRRELEQLASfllensfrlPLDPALEVTGV-DVRSCSY 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  782 MDSKMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHS 861
Cdd:cd05166    70 FNSNALPLKLVFRNADPR-AEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEA 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  862 DTIANIQlnkSNMAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHI 940
Cdd:cd05166   149 ETLREIQ---TEHGLTGSFKDRPLADWLQKHNPSElEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHI 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  941 DFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELS 1020
Cdd:cd05166   226 DFGKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGD-KPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT 304

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 568930781 1021 cSKDIQYLKDSLALGKTEEEALKHFRVKFNEALReSWKTKVNWLAHNV 1068
Cdd:cd05166   305 -QDDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 707-1070 1.38e-108

Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kalpha plays an important role in insulin signaling. It also mediates physiologic heart growth and provides protection from stress. Activating mutations of PI3Kalpha is associated with diverse forms of cancer at high frequency. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 343.19  E-value: 1.38e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  707 HMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKM 786
Cdd:cd05175     4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNL-RLEECRIMSSAK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  787 KPLWIMYSSEEAGSA---GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDT 863
Cdd:cd05175    83 RPLWLNWENPDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHT 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  864 IANIQLnKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFG 943
Cdd:cd05175   163 IMQIQC-KGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFG 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  944 HFLGNFKTKFGINRERVPFILTYDFVHVIQQG--KTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSC 1021
Cdd:cd05175   242 HFLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQS 321

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 568930781 1022 SKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 1070
Cdd:cd05175   322 FDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 758-1068 7.77e-106

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 335.68  E-value: 7.77e-106
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  758 SHLQSPLDPStLLEEVCSVEQCTFMDSKMKPLWIMYS--SEEAGSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEG 835
Cdd:cd00894    53 ESFRVPYDPG-LRAGALVIEKCKVMASKKKPLWLEFKcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETES 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  836 LDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCV 914
Cdd:cd00894   132 LDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCV 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  915 ATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAY 994
Cdd:cd00894   210 ATFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAY 289

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568930781  995 TILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNV 1068
Cdd:cd00894   290 LALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 5.11e-92

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 291.14  E-value: 5.11e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  314 VSLWSLEQPFSIELIEGRKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCF 392
Cdd:cd08693     1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  393 ALYAVVEKAKKARSTK----KKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESA 468
Cdd:cd08693    81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                         170
                  ....*....|...
gi 568930781  469 AALVIYLPEVAPH 481
Cdd:cd08693   161 TALHISFPEYKPE 173
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 749-1070 8.33e-85

Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 278.79  E-value: 8.33e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  749 RQETYMEALSHLQS---------PLDPSTLLEEVcSVEQCTFMDSKMKPLWI-MYSSEEAGSAGNVgiIFKNGDDLRQDM 818
Cdd:cd05176    29 RQVALQDGMERVQSffqknkcrlPLSPSLVAKEL-NIKACSFFSSNAVPLKVaLVNADPLGEEINV--MFKVGEDLRQDM 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  819 LTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNksnMAATAAFNKDALLNWLKSKNPGE-A 897
Cdd:cd05176   106 LALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVE---YGVTGSFKDKPLAEWLRKYNPSEeE 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  898 LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKT 977
Cdd:cd05176   183 YEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEK 262

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  978 NNSeKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESW 1057
Cdd:cd05176   263 PTI-RFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQTTDAEATIFF-TRLIESSLGSV 340

                         330
                  ....*....|...
gi 568930781 1058 KTKVNWLAHNVSK 1070
Cdd:cd05176   341 ATKFNFFIHNLAQ 353
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 806-1023 1.04e-80

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 263.00  E-value: 1.04e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    806 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 870
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    871 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 937
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    938 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 1017
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 568930781   1018 ELSCSK 1023
Cdd:smart00146  235 DWRSGK 240
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 709-1053 3.85e-79

Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class III PI3Ks, also called Vps34 (vacuolar protein sorting 34), contain an N-terminal lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They phosphorylate only the substrate PtdIns. They interact with a regulatory subunit, Vps15, to form a membrane-associated complex. Class III PI3Ks are involved in protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 262.85  E-value: 3.85e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  709 KVLMKQGEALSKLKALNDFVKVSSQKTTKpQTKEMMHMCMRQETYMEALSH-LQSPLDPSTLLEEVCSvEQCTFMDSKMK 787
Cdd:cd00896     2 EALKRQQEFVDRLRSLMKEVKNEKGSRDK-KIERLRELLSDSELGLLLFFEpLPLPLDPSVKVTGIIP-EKSTVFKSALM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  788 PLWIMYSSEEAGSagnVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 867
Cdd:cd00896    80 PLKLTFKTLDGGE---YKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  868 qLNKSNmaataafnkdALLNWLKSKNPGEA-----LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDF 942
Cdd:cd00896   157 -LKKYG----------SILNFLRKHNPDESgpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDF 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  943 GHFLGN----FKTKFGINRERVPFIltydfvhviqqGKTnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPE 1018
Cdd:cd00896   226 GYILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPD 293

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 568930781 1019 LSCSKD--IQYLKDSLALGKTEEEALKHFRVKFNEAL 1053
Cdd:cd00896   294 IALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 709-1070 7.75e-79

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 262.14  E-value: 7.75e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  709 KVLMKQGEALSKLKALNDFVKVSSqkttKPQTKEMMHMCMRQ-ETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKMK 787
Cdd:cd05177     2 KEFSKETKLISILIDAAEKVKTAS----DTRRKEVLKREASRlEDFFQDVVSCCLPLNPALRVKGI-DADACSYFTSNAA 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  788 PLWIMYSSEEAgSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 867
Cdd:cd05177    77 PLKISFINANP-LAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKI 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  868 QlNKSNMAATaaFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 946
Cdd:cd05177   156 H-RESGLIGP--LKENTIEKWFHMHNKLKEdYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFL 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  947 GNFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQ 1026
Cdd:cd05177   233 GHAQTFGSIKRDRAPFIFTSEMEYFITEGG-KKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLK 311

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....
gi 568930781 1027 YLKDSLALGKTEEEALKHFRVKFNEALrESWKTKVNWLAHNVSK 1070
Cdd:cd05177   312 YVYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTLAQ 354
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-713 2.34e-78

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 254.49  E-value: 2.34e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAqvsreggsgrqprgrwtvpah 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVA--------------------- 62

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    584 pylttklsQMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLL 663
Cdd:smart00145   63 --------QALSLLLSWAPLDPEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLL 134

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|
gi 568930781    664 GRALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMK 713
Cdd:smart00145  135 ERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEAYLRGCGTHLKELLK 184
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 804-1020 2.31e-76

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 251.09  E-value: 2.31e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   804 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAAF 880
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   881 N-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESG 935
Cdd:pfam00454   82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   936 QLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG 1015
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*
gi 568930781  1016 LPELS 1020
Cdd:pfam00454  236 LPDWS 240
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 763-1070 1.07e-74

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 251.07  E-value: 1.07e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  763 PLDPSTLLEEVcSVEQCTFMDSKMKPLWIMYSSEEAgSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTP 842
Cdd:cd00895    53 PLSPSLLVKGI-VPRDCSYFNSNAVPLKLSFQNVDP-LGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVI 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  843 YGCLPTGDRTGLIEVVLHSDTIANIQLNKsnmAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGI 921
Cdd:cd00895   131 FRCFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPTEdEYEKAVENFIYSCAGCCVATYVLGI 207

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  922 GDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHG 1001
Cdd:cd00895   208 CDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSS-RFHDFVDLCCQAYNLIRKHT 286

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568930781 1002 LLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWKTKVNWLAHNVSK 1070
Cdd:cd00895   287 HLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYF-TRLIESSLGSVATKLNFFIHNLAQ 354
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 505-704 2.87e-71

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 234.13  E-value: 2.87e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  505 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQvsreggsgrqprgrwtvpahp 584
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQ--------------------- 58

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  585 ylttklsqMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLG 664
Cdd:cd00872    59 --------MYQLLKRWPKLKPEQALELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLK 130

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 568930781  665 RALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGS 704
Cdd:cd00872   131 RALRNQRIGHFFFWHLRSEMHNPSVSQRFGLLLEAYLRGC 170
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 499-713 5.23e-57

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 194.86  E-value: 5.23e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   499 ERGRITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQVsreggsgrqprgrw 578
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAEA-------------- 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   579 tvpahpylttkLSQMLYllcsWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCEL 658
Cdd:pfam00613   66 -----------LSLLLK----WAPIDPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYL 130

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568930781   659 TKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMK 713
Cdd:pfam00613  131 SRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 807-1060 9.39e-50

Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIalpha is a 220 kDa protein found in the plasma membrane and the endoplasmic reticulum (ER). The role of PI4KIIIalpha in the ER remains unclear. In the plasma membrane, it provides PtdIns(4)P, which is then converted by PI5Ks to PtdIns(4,5)P2, an important signaling molecule. Vertebrate PI4KIIIalpha is also part of a signaling complex associated with P2X7 ion channels. The yeast homolog, Stt4p, is also important in regulating the conversion of phosphatidylserine to phosphatidylethanolamine at the ER and Golgi interface. Mammalian PI4KIIIalpha is highly expressed in the nervous system. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 178.56  E-value: 9.39e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  807 IFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSdtianiqlnKS--NMAATAAFNkda 884
Cdd:cd05167    53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNS---------KSrdQIGRETDNG--- 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  885 LLNWLKSK--NPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGhFL------GNFKTkfgi 955
Cdd:cd05167   121 LYEYFLSKygDEStPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIfeispgGNLGF---- 195

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  956 nrERVPFILTYDFVHVIqqGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPelsC--SKDIQYLKDSLA 1033
Cdd:cd05167   196 --ESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLP---CfrGQTIKNLRERFA 268

                         250       260
                  ....*....|....*....|....*..
gi 568930781 1034 LGKTEEEALKHFRVKFNEALrESWKTK 1060
Cdd:cd05167   269 LEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 803-1060 9.95e-48

Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. There are two types of PI4Ks, types II and III. Type II PI4Ks lack the characteristic catalytic kinase domain present in PI3Ks and type III PI4Ks, and are excluded from this family. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 172.06  E-value: 9.95e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  803 NVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIAniQLNKSNMAATAAFNk 882
Cdd:cd00893    27 LVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSID--SLKKKLDSFNKFVS- 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  883 daLLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERVPF 962
Cdd:cd00893   104 --LSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPF 179

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  963 ILTYDFVHVIqqgKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEAL 1042
Cdd:cd00893   180 KLSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELE 256

                         250
                  ....*....|....*...
gi 568930781 1043 KHFRVKFNEALReSWKTK 1060
Cdd:cd00893   257 VYVLSLINKSLD-NWRTR 273
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 506-685 1.83e-47

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in a variety of fundamental cellular processes and can be divided into three main classes, defined by their substrate specificity and domain architecture.


Pssm-ID: 238440  Cd Length: 152  Bit Score: 166.24  E-value: 1.83e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  506 EEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVaqvsreggsgrqprgrwtvpahpy 585
Cdd:cd00864     2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNV-PKALPKLLKSVNWNDDEEV------------------------ 56

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  586 lttklSQMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGR 665
Cdd:cd00864    57 -----SELYQLLKWWAPLSPEDALELLSPKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLER 131

                         170       180
                  ....*....|....*....|
gi 568930781  666 ALANRKIGHFLFWHLRSEMH 685
Cdd:cd00864   132 ALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 804-1060 8.48e-45

Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIbeta (also called Pik1p in yeast) is a 110 kDa protein that is localized to the Golgi and the nucleus. It is required for maintaining the structural integrity of the Golgi complex (GC), and is a key regulator of protein transport from the GC to the plasma membrane. PI4KIIIbeta also functions in the genesis, transport, and exocytosis of synaptic vesicles. The Drosophila PI4KIIIbeta is essential for cytokinesis during spermatogenesis. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 163.81  E-value: 8.48e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  804 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVlhSDTIANIQLNKSNMAATaafnkd 883
Cdd:cd05168    31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETI--PDTVSIDSLKKRFPNFT------ 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  884 ALLNWLKSK---NPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERV 960
Cdd:cd05168   103 SLLDYFERTfgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETA 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  961 PFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG-LPELSCSKD--IQYLKDSLALGKT 1037
Cdd:cd05168   181 PFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNLT 257

                         250       260
                  ....*....|....*....|...
gi 568930781 1038 EEEALKHFRVKFNEALReSWKTK 1060
Cdd:cd05168   258 EEECAQFVDSLIDKSLN-NWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 776-1011 4.05e-43

Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family include PI3K, phosphoinositide 4-kinase (PI4K), PI3K-related protein kinases (PIKKs), and TRansformation/tRanscription domain-Associated Protein (TRAPP). PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives, while PI4K catalyze the phosphorylation of the 4-hydroxyl of PtdIns. PIKKs are protein kinases that catalyze the phosphorylation of serine/threonine residues, especially those that are followed by a glutamine. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI4Ks produce PtdIns(4)P, the major precursor to important signaling phosphoinositides. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PI3K-like catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270621 [Multi-domain]  Cd Length: 216  Bit Score: 156.34  E-value: 4.05e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  776 VEQCTFMDSKMKPLWImyssEEAGSAGN-VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGL 854
Cdd:cd00142     5 VGILKVIHSKQRPKKI----TLIGADGKtYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  855 IEVVLHSDTIANiqlnksnmaataafnkdaLLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRE 933
Cdd:cd00142    81 IEIVKDAQTIED------------------LLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEP 142

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568930781  934 SGQLFHIDFGHFLGNFKTKFGInrERVPFILTYDFVHVIQQGKTNNsekfeRFRGYCERAYTILRRHGLLFLHLFALM 1011
Cdd:cd00142   143 SGNIFHIDFGFIFSGRKLAEGV--ETVPFRLTPMLENAMGTAGVNG-----PFQISMVKIMEILREHADLIVPILEHS 213
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 314-483 6.95e-40

C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes of PI3Ks. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains members with the first C2 repeat, C2A, and a type-I topology, as well as some with a single C2 repeat.


Pssm-ID: 176026  Cd Length: 156  Bit Score: 144.81  E-value: 6.95e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  314 VSLWSLEQPFSIEL--IEGRKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLC 391
Cdd:cd08380     1 KSLWDINFNLRIKIhgITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  392 FALYAVvekakkarsTKKKSKKaDCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEkgellNPAGTVRGNPNTESAAAL 471
Cdd:cd08380    81 LSIYAV---------SEPGSKK-EVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPCNNSNENSTRL 145

                         170
                  ....*....|..
gi 568930781  472 VIYLPEVaPHPV 483
Cdd:cd08380   146 LIELPEF-SKPV 156
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
709-1045 1.88e-36

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 150.32  E-value: 1.88e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  709 KVLMKQGE--ALSKLKALNDFVKVSSQKTTKPQTKEMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCSvEQCT 780
Cdd:COG5032  1698 KIRKKFKIdiSLLNLSRKLYISVLRSIRKRLKRLLELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEP-EVSV 1776

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  781 FMDSKMKPLWIMYSseeaGSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLI 855
Cdd:COG5032  1777 VKSHLQRPRRLTIR----GSDGKLySFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGII 1852

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  856 EVVLHSDTIANI------QLNKS-NMAATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTL 907
Cdd:COG5032  1853 EWVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFAR 1932

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  908 SCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERF 986
Cdd:COG5032  1933 SLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSF 2006

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568930781  987 RGYCERAYTILRRHGLLFLHLFALMRAAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 1045
Cdd:COG5032  2007 RELCETAFRALRKNADSLMNVLELFVRDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 6.89e-36

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 130.33  E-value: 6.89e-36
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568930781    34 FPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 315-467 1.62e-34

C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, alpha isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176043  Cd Length: 158  Bit Score: 129.53  E-value: 1.62e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  315 SLWSLEQPFSIELIEGRKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVNvCSEPVWKQRLEFDISVCDLPRMARLCFAL 394
Cdd:cd08398     2 SLWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLCDNVNTQRVP-CSNPRWNEWLDYDIYIPDLPRSARLCLSI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568930781  395 YAVvekakkarSTKKKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPsVPDEKGELLNPAGTVRGNPNTES 467
Cdd:cd08398    81 CSV--------KGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWP-VPHGLEDLLNPIGVTGSNPNKDT 144
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 7.50e-32

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 120.09  E-value: 7.50e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   182 LLRVSNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVEQpeEYALQVNGRHEYLYGNYPLCHFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 568930781   262 ICSCLHSGLTPHLTMVHSSS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 312-407 2.34e-30

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 115.52  E-value: 2.34e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    312 SSVSLWSLEQPFSIELIEGRKVNADERM-KLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARL 390
Cdd:smart00142    4 ESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARL 83

                            90
                    ....*....|....*..
gi 568930781    391 CFALYAVVEKAKKARST 407
Cdd:smart00142   84 CITIYAVKNPSKGSEFG 100
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 504-685 8.30e-24

Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III phosphorylate phosphoinositol (PtdIns) only. The prototypical PI3K class III, yeast Vps34, is involved in trafficking proteins from Golgi to the vacuole.


Pssm-ID: 238442  Cd Length: 166  Bit Score: 98.94  E-value: 8.30e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVAQVsreggsgrqprgrwtvpah 583
Cdd:cd00870     7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNN-KKALTKFLKSVNWSDEQEVKQA------------------- 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  584 pylttklsqmLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESY-------LDC 656
Cdd:cd00870    67 ----------LELMPKWAKIDIEDALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDS 136

                         170       180
                  ....*....|....*....|....*....
gi 568930781  657 ELTKFLLGRALANRKIGHFLFWHLRSEMH 685
Cdd:cd00870   137 PLADFLIERALKNPKLANFLYWYLKVELE 165
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 807-1001 1.23e-22

Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members include ATM (Ataxia telangiectasia mutated), ATR (Ataxia telangiectasia and Rad3-related), TOR (Target of rapamycin), SMG-1 (Suppressor of morphogenetic effect on genitalia-1), and DNA-PK (DNA-dependent protein kinase). PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). They show strong preference for phosphorylating serine/threonine residues followed by a glutamine and are also referred to as (S/T)-Q-directed kinases. They all contain a FATC (FRAP, ATM and TRRAP, C-terminal) domain. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PIKK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 97.34  E-value: 1.23e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  807 IFKNGDDLRQDMLTLQMIQLMDVLWKQEG----LDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIqlnksnmaataaFNK 882
Cdd:cd05164    33 LVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLIEWVDNTTTLKPV------------LKK 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  883 DAllnWLKSKNPGEALDrAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTkFGINrERVP 961
Cdd:cd05164   101 WF---NETFPDPTQWYE-ARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFNKGKT-LPVP-EIVP 174

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 568930781  962 FILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRRHG 1001
Cdd:cd05164   175 FRLTRNIINGMGPTGVEGL-----FRKSCEQVLRVFRKHK 209
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 505-685 2.18e-22

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


Pssm-ID: 238441  Cd Length: 169  Bit Score: 95.22  E-value: 2.18e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  505 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLlvtkwnkhedvaqvsregGSgrqprgrwtvpAHP 584
Cdd:cd00869     1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNE-PNALPLVL------------------AS-----------APS 50

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  585 YLTTKLSQMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLG 664
Cdd:cd00869    51 WDWANLMDVYQLLHQWAPLRPLIALELLLPKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLS 130

                         170       180
                  ....*....|....*....|.
gi 568930781  665 RALANRKIGHFLFWHLRSEMH 685
Cdd:cd00869   131 RSLVSLRFAHELYWLLKDALD 151
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 339-448 2.49e-22

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 93.97  E-value: 2.49e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781   339 MKLVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarstkKKSKKADCP 417
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVP 71

                           90       100       110
                   ....*....|....*....|....*....|.
gi 568930781   418 IAWANLMLFDYKDQLKTGERCLYMWPSVPDE 448
Cdd:pfam00792   72 IGWVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 2.88e-21

PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.


Pssm-ID: 197539  Cd Length: 78  Bit Score: 88.69  E-value: 2.88e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568930781     31 YLNFPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 782-1001 1.62e-20

Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic domain, and a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. It is also called FRAP (FK506 binding protein 12-rapamycin associated protein). TOR is a central component of the eukaryotic growth regulatory network. It controls the expression of many genes transcribed by all three RNA polymerases. It associates with other proteins to form two distinct complexes, TORC1 and TORC2. TORC1 is involved in diverse growth-related functions including protein synthesis, nutrient use and transport, autophagy and stress responses. TORC2 is involved in organizing cytoskeletal structures. TOR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The TOR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 92.93  E-value: 1.62e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  782 MDSKMKP--LWIMysseeaGSAGNVgIIF--KNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTG 853
Cdd:cd05169    11 ITSKQRPrkLTIV------GSDGKE-YKFllKGHEDLRLDERVMQLFGLVNTLLKNDsetsRRNLSIQRYSVIPLSPNSG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  854 LIEVVLHSDTIA----------NIQLN--KSNMAATA-------------AFN-----------KDALlnWLKSKNPGEA 897
Cdd:cd05169    84 LIGWVPGCDTLHslirdyrekrKIPLNieHRLMLQMApdydnltliqkveVFEyalentpgddlRRVL--WLKSPSSEAW 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  898 LDRAIeEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFG-------HflgnfKTKFginRERVPFILTYDFV 969
Cdd:cd05169   162 LERRT-NFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRMLV 232

                         250       260       270
                  ....*....|....*....|....*....|..
gi 568930781  970 HVIQQGKTNNSekferFRGYCERAYTILRRHG 1001
Cdd:cd05169   233 NAMEVSGVEGT-----FRSTCEDVMRVLRENK 259
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 777-973 4.88e-20

Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, containing the Ku70/80 subunit, and a catalytic subunit, which contains a NUC194 domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is part of a multi-component system involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology. DNA-PK functions as a molecular sensor for DNA damage that enhances the signal via phosphorylation of downstream targets. It may also act as a protein scaffold that aids the localization of DNA repair proteins to the site of DNA damage. DNA-PK also plays a role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. DNA-PK is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The DNA-PK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 90.33  E-value: 4.88e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  777 EQCTFMDSKMKPLWI-MYSSEEAGSAgnvgIIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDR 851
Cdd:cd05172     6 PRVLVLSSKRRPKRItIRGSDEKEYK----FLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  852 TGLIEVVLHSDTIANIqlnksnmaataaFNKDALLNWLK--SKNPgEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNI 929
Cdd:cd05172    82 LGLIEWVDNTTPLKEI------------LENDLLRRALLslASSP-EAFLALRSNFARSLAAMSICGYILGIGDRHLSNF 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 568930781  930 MI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQ 973
Cdd:cd05172   149 LVdLSTGRLIGIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQ 192
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 807-1000 6.08e-19

Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA double strand breaks (DSBs) caused by radiation. It is activated at the site of a DSB and phosphorylates key substrates that trigger pathways that regulate DNA repair and cell cycle checkpoints at the G1/S, S phase, and G2/M transition. Patients with the human genetic disorder Ataxia telangiectasia (A-T), caused by truncating mutations in ATM, show genome instability, increased cancer risk, immunodeficiency, compromised mobility, and neurodegeneration. A-T displays clinical heterogeneity, which is correlated to the degree of retained ATM activity. ATM contains a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATM catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270715 [Multi-domain]  Cd Length: 282  Bit Score: 88.37  E-value: 6.08e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  807 IFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNKSN--------- 873
Cdd:cd05171    33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSksgaharyr 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  874 ------------MAATAAFNKDALLN-----------------WLKSKNPGEALDRaIEEFTLSCAGYCVATYVLGIGDR 924
Cdd:cd05171   113 pkdwtastcrkkMREKAKASAEERLKvfdeicknfkpvfrhffLEKFPDPSDWFER-RLAYTRSVATSSIVGYILGLGDR 191

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  925 HSDNIMI-RESGQLFHIDFG-HFlgnfktKFGIN---RERVPFILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRR 999
Cdd:cd05171   192 HLNNILIdQKTGELVHIDLGiAF------EQGKLlpiPETVPFRLTRDIVDGMGITGVEGV-----FRRCCEETLRVLRE 260


                  .
gi 568930781 1000 H 1000
Cdd:cd05171   261 N 261
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 345-479 3.27e-18

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175979  Cd Length: 171  Bit Score: 83.18  E-value: 3.27e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  345 AGLFHGNEMLCKTVSSSEVNVCSE----PVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTKKKSKKadcPIAW 420
Cdd:cd04012    35 CSLYHGGRLLCSPVTTKPVKITKSffprVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGGSNKQRMGPE---ELGW 111

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568930781  421 ANLMLFDYKDQLKTGERCLYMWPSvpdEKGELLNPAGTVrgNPNTESAAALVIYLPEVA 479
Cdd:cd04012   112 VSLPLFDFRGVLRQGSLLLGLWPP---SKDNPLGPAPPP--LFEQPDRVILQIDFPSSA 165
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 313-483 2.09e-16

C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, gamma isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176044  Cd Length: 178  Bit Score: 78.41  E-value: 2.09e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  313 SVSLWSLEQPFSIEL----IEGRKVNADerMKLVVQAGLFHGNEMLCKTVSSSEvNVCSEPVWKQRLEFDISVCDLPRMA 388
Cdd:cd08399     2 TVSLWDCDRKFRVKIlgidIPVLPRNTD--LTVFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  389 RLCFALYAV----VEKAKKARSTKKKSKKADCPIAWANLMLFDYKDQLKTGERCLYMW--PSVPDEKGELLNPAGTVRGN 462
Cdd:cd08399    79 LLNLQIYCGkapaLSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWqiSGKGEDQGSVNADKLTSATN 158

                         170       180
                  ....*....|....*....|.
gi 568930781  463 PNTESAAALVIYLPEVApHPV 483
Cdd:cd08399   159 PDKENSMSISILLDNYC-HPV 178
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 782-1000 2.47e-16

Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to as Mei-41 (Drosophila), Esr1/Mec1p (Saccharomyces cerevisiae), Rad3 (Schizosaccharomyces pombe), and FRAP-related protein (human). ATR contains a UME domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. Together with its downstream effector kinase, Chk1, ATR plays a central role in regulating the replication checkpoint. ATR stabilizes replication forks by promoting the association of DNA polymerases with the fork. Preventing fork collapse is essential in preserving genomic integrity. ATR also plays a role in normal cell growth and in response to DNA damage. ATR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 79.47  E-value: 2.47e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  782 MDSKMKPLWIMYsseeAGSAGN-VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQ----EGLDLRMTPYGCLPTGDRTGLIE 856
Cdd:cd00892    11 MPSLQKPKKITL----VGSDGKkYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLNEECGIIE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  857 VVLHSDTIANIqLNKsnmaataaFNKDALLNWLKSK--NPGEALdRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RE 933
Cdd:cd00892    87 WVPNTVTLRSI-LST--------LYPPVLHEWFLKNfpDPTAWY-EARNNYTRSTAVMSMVGYILGLGDRHGENILFdST 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568930781  934 SGQLFHIDFGHFLGNFKTkFGInRERVPFILTYDFVHVIqqGKTnnseKFE-RFRGYCERAYTILRRH 1000
Cdd:cd00892   157 TGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAM--GVT----GVEgTFRRTCEVTLRVLREN 216
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 183-281 3.55e-16

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 75.44  E-value: 3.55e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781    183 LRVSNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPlVEQPEEYALQVNGRHEYLYGNYPLCHFQYI 262
Cdd:smart00144   11 LKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQV-DPTSEDYILKVCGRDEYLLGDHPLGSFEYI 89

                            90
                    ....*....|....*....
gi 568930781    263 CSCLHSGLTPHLTMVHSSS 281
Cdd:smart00144   90 RNCLKNGTEPHLVLMTLSA 108
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 799-1008 9.93e-09

Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C-terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD. In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The SMG-1 catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270714  Cd Length: 304  Bit Score: 58.04  E-value: 9.93e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  799 GSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLW----KQEGLDLRMTPYGCLPTGDRTGLIEVV-------------LH 860
Cdd:cd05170    24 GSDGKRyPYLFKGLEDLHLDERIMQFLSIVNAMLasdnEHRRRRYRARHYSVTPLGPRSGLIQWVdgatplfslykrwQQ 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  861 SDTIANIQLNKSNMAATAA--------FNK---------------------DAL---LNWLKSKNPGEALDRAI------ 902
Cdd:cd05170   104 RRAAAQAQKNQDSGSTPPPvprpselfYNKlkpalkaagirkstsrrewplEVLrqvLEELVAETPRDLLARELwcssps 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  903 --------EEFTLSCAGYCVATYVLGIGDRHSDNIMIR-ESGQLFHIDF------GHFLgnfktkfginR--ERVPFILT 965
Cdd:cd05170   184 saewwrvtQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLT 253

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 568930781  966 YDFVHVIqqGKTNnsekFE-RFRGYCERAYTILRRHGLLFLHLF 1008
Cdd:cd05170   254 QNIEHAL--GPTG----VEgTFRLSCEQVLKILRKGRETLLTLL 291
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 799-943 7.81e-08

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: 52.44  E-value: 7.81e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  799 GSAGNVGIIFKNGDDlRQDMLTLQMIQLMDVLWKQEGLDLrmTPYGCLPTGDRTG----LIEVVlhsdtianiqlnksnm 874
Cdd:cd13968    14 GECTTIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELV---------------- 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568930781  875 aataafnKDALLNWLKSKnpGEALDRAIEEFTLSCAGYCVATYV--LGIGDRHSDNIMIRESGQLFHIDFG 943
Cdd:cd13968    75 -------KGGTLIAYTQE--EELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 341-448 9.51e-07

C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. These are the only domains identified in the class III PI3Ks present in this cd. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176042  Cd Length: 159  Bit Score: 49.55  E-value: 9.51e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  341 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKarstkkkskkadCPIAW 420
Cdd:cd08397    32 LFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKA------------VPFGG 99

                          90       100
                  ....*....|....*....|....*...
gi 568930781  421 ANLMLFDYKDQLKTGERCLYMWPSVPDE 448
Cdd:cd08397   100 TTLSLFNKDGTLRRGRQKLRVWPDVEAD 127
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 591-684 1.85e-04

Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. PI4K phosphorylates hydroxylgroup at position 4 on the inositol ring of phosphoinositide, the first commited step in the phosphatidylinositol cycle.


Pssm-ID: 238443  Cd Length: 175  Bit Score: 43.50  E-value: 1.85e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568930781  591 SQMLYLLCsWPELPVLSALELLDFSFP-DCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESylDCELTKFLLGRALAN 669
Cdd:cd00871    57 PDLKYLLY-WAPVSPVQALSLFTPQYPgHPLVLQYAVRVLESYPVETVFFYIPQIVQALRYDK--MGYVEEYILETAKRS 133

                          90
                  ....*....|....*
gi 568930781  670 RKIGHFLFWHLRSEM 684
Cdd:cd00871   134 QLFAHQIIWNMQTNC 148
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 904-965 5.92e-04

Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs to the the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. It contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain and has a large molecular weight. Unlike most PIKK proteins, however, it contains an inactive PI3K-like pseudokinase domain, which lacks the conserved residues necessary for ATP binding and catalytic activity. TRRAP also contains many motifs that may be critical for protein-protein interactions. TRRAP is a common component of many histone acetyltransferase (HAT) complexes, and is responsible for the recruitment of these complexes to chromatin during transcription, replication, and DNA repair. TRRAP also exists in non-HAT complexes such as the p400 and MRN complexes, which are implicated in ATP-dependent remodeling and DNA repair, respectively. The TRRAP pseudokinase domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270707  Cd Length: 252  Bit Score: 42.89  E-value: 5.92e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568930781  904 EFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFgHFLGNFKTKFGINRERVPFILT 965
Cdd:cd05163   140 QFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDF-LPSINSQGPLLDNNEPVPFRLT 201
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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