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Conserved domains on  [gi|41055186|ref|NP_957493|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [Danio rerio]

Protein Classification

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 ...
 676-1038 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: 786.55  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  676 IFHIKSLMKQNEALNKMKALNDFVKSASQKATRIQTTEDMKVCIKQETYMEALSDVVSPLSPSIILCELCADKCKFMDSK 755
Cdd:cd05174    1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  756 MKPLWLMYKSKY---DSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIAN 832
Cdd:cd05174   81 MKPLWIMYSSEEagaGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIAN 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  833 IQRNNSNSAATAAFNKDALLNWLKSKNPGDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 912
Cdd:cd05174  161 IQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  913 GNFKSKFGINRERVPFILTYDFVHVIQEGRTNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKDIQ 992
Cdd:cd05174  241 GNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQ 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 41055186  993 YLKDSLALGKSEEEALKNFKVKFNEALRESWKTKVNWMMHTFAKDN 1038
Cdd:cd05174  321 YLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 505-676 2.83e-94

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: 296.53  E-value: 2.83e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  505 KEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRLKyPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELLD 584
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKK-PQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  585 YSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLRF 664
Cdd:cd00872   80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                        170
                 ....*....|..
gi 41055186  665 GLILEAYCRGSI 676
Cdd:cd00872  160 GLLLEAYLRGCG 171
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 315-481 2.40e-79

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: 256.08  E-value: 2.40e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  315 CSLWSIQEPFYIYLLQGSRVNA-DEGMKLVVQAGLFHGSELLCKVVTSNEVSVCFDPVWDQKLVFDINVSDLPRMSRLCF 393
Cdd:cd08693    1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  394 ALYGVIE-----KTKKRPTKKKNKRADCPLAWVNTMVFDYKDQLKTGEFSLSTWPSVPDDKGDLLNPMGTVEKNPNIDST 468
Cdd:cd08693   81 AIYEVSKkakgkRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                        170
                 ....*....|...
gi 41055186  469 AGLLIRFPNIRPH 481
Cdd:cd08693  161 TALHISFPEYKPE 173
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.23e-34

PI3-kinase family, p85-binding domain;


:

Pssm-ID: 460483  Cd Length: 74  Bit Score: 126.48  E-value: 1.23e-34
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 41055186     34 FTVACSDTISTIKKMLWKNAKNEPLFSALSDPDAYVFTCINMTAEREELEDEQRRLCDVRPFLPILRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd super family cl02484
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 188-280 1.09e-19

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).


The actual alignment was detected with superfamily member pfam00794:

Pssm-ID: 413336  Cd Length: 106  Bit Score: 85.04  E-value: 1.09e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    188 KIFVNVKFEGSEETFVLQQDPQDLPVVLKRNALRKKSTVFRSVKQEKpeDYSLQVNERWEFIYGKYPLCQFKYIFTCLHG 267
Cdd:pfam00794   16 KLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEYIRNCLKS 93

                           90
                   ....*....|...
gi 41055186    268 GLTPHLTMVHYSS 280
Cdd:pfam00794   94 GREPHLTLVEQSS 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 ...
 676-1038 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: 786.55  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  676 IFHIKSLMKQNEALNKMKALNDFVKSASQKATRIQTTEDMKVCIKQETYMEALSDVVSPLSPSIILCELCADKCKFMDSK 755
Cdd:cd05174    1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  756 MKPLWLMYKSKY---DSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIAN 832
Cdd:cd05174   81 MKPLWIMYSSEEagaGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIAN 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  833 IQRNNSNSAATAAFNKDALLNWLKSKNPGDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 912
Cdd:cd05174  161 IQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  913 GNFKSKFGINRERVPFILTYDFVHVIQEGRTNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKDIQ 992
Cdd:cd05174  241 GNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQ 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 41055186  993 YLKDSLALGKSEEEALKNFKVKFNEALRESWKTKVNWMMHTFAKDN 1038
Cdd:cd05174  321 YLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 505-676 2.83e-94

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: 296.53  E-value: 2.83e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  505 KEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRLKyPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELLD 584
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKK-PQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  585 YSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLRF 664
Cdd:cd00872   80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                        170
                 ....*....|..
gi 41055186  665 GLILEAYCRGSI 676
Cdd:cd00872  160 GLLLEAYLRGCG 171
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 315-481 2.40e-79

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: 256.08  E-value: 2.40e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  315 CSLWSIQEPFYIYLLQGSRVNA-DEGMKLVVQAGLFHGSELLCKVVTSNEVSVCFDPVWDQKLVFDINVSDLPRMSRLCF 393
Cdd:cd08693    1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  394 ALYGVIE-----KTKKRPTKKKNKRADCPLAWVNTMVFDYKDQLKTGEFSLSTWPSVPDDKGDLLNPMGTVEKNPNIDST 468
Cdd:cd08693   81 AIYEVSKkakgkRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                        170
                 ....*....|...
gi 41055186  469 AGLLIRFPNIRPH 481
Cdd:cd08693  161 TALHISFPEYKPE 173
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 772-989 1.65e-78

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: 256.46  E-value: 1.65e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     772 IIFKNGDDLRQDMLTLQMIQIMDILWKTE----GLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQRNN---------- 837
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     838 ------------SNSAATAAFNKDALLNWLKSKNPGDKLD--QAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 903
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     904 FHIDFGHFLGNFKSKFGiNRERVPFILTYDFVHVIqegrtNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLP 983
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 41055186     984 ELNSSK 989
Cdd:smart00146  235 DWRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 769-987 3.80e-72

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: 239.15  E-value: 3.80e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    769 SVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDL-RMQPYGCLSTGNKTGLIEVVKNSDTIANIQRN--NSNSAATAA 845
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    846 FN-----------------------KDALLNWLKSKNPG-DKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RES 900
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    901 GQLFHIDFGHFLGNFKSKFGINrERVPFILTYDFVHVIqegrtNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAA 980
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*..
gi 41055186    981 GLPELNS 987
Cdd:pfam00454  235 GLPDWSI 241
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-684 1.25e-71

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: 235.61  E-value: 1.25e-71
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     504 TKEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRLKYPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELL 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     584 DYSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLR 663
Cdd:smart00145   84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIR 163

                           170       180
                    ....*....|....*....|.
gi 41055186     664 FGLILEAYCRGSIFHIKSLMK 684
Cdd:smart00145  164 FGLLLEAYLRGCGTHLKELLK 184
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-684 5.28e-60

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: 203.33  E-value: 5.28e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    504 TKEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRLKyPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELL 583
Cdd:pfam00613    6 NEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLV-PKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    584 DYSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLR 663
Cdd:pfam00613   85 DPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPR 164

                          170       180
                   ....*....|....*....|.
gi 41055186    664 FGLILEAYCRGSIFHIKSLMK 684
Cdd:pfam00613  165 FGSLLELYLRSCGTSLLGLNK 185
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.23e-34

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 126.48  E-value: 1.23e-34
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 41055186     34 FTVACSDTISTIKKMLWKNAKNEPLFSALSDPDAYVFTCINMTAEREELEDEQRRLCDVRPFLPILRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
597-1009 6.94e-34

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 141.84  E-value: 6.94e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  597 IRCLRKLPDDKLFQYLLQLVQVLKYESyldcdltsFLLERALANKKIGHFLFWHL-RSEMHVPSVSLRFGLILEAYCRgs 675
Cdd:COG5032 1628 IRIAYPLLHLLFEPILAQLLSRLSSEN--------NKISVALLIDKPLHEERENFpSGLSLSSFQSSFLKELIKKSPR-- 1697

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  676 ifHIKSLMKQNEALNK--MKALNDFVKSASQKATRIQTTEDMKVCIKQETYMEALSDVV----SPLSPSIILCELCADKC 749
Cdd:COG5032 1698 --KIRKKFKIDISLLNlsRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFHAFLEIKLpgqyLLDKPFVLIERFEPEVS 1775

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  750 KFMDSKMKPLWLMYK-SKYDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGL----DLRMQPYGCLSTGNKTGLIEVV 824
Cdd:COG5032 1776 VVKSHLQRPRRLTIRgSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWV 1855

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  825 KNSDTIANI------QRNNSNSAAT---------------------AAFNKDALLNWLKSKNPGD-KLDQAIEEFTLSCA 876
Cdd:COG5032 1856 PNSDTLHSIlreyhkRKNISIDQEKklaarldnlklllkdefftkaTLKSPPVLYDWFSESFPNPeDWLTARTNFARSLA 1935

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  877 GYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKSKFGINrERVPFILTYDFVHVI----QEGrtnnsekfeR 951
Cdd:COG5032 1936 VYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMgvsgVEG---------S 2005

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 41055186  952 FRVCCEQAYKILCRNGTLFVNLFALMK------AAGLPELN--SSKDIQYLKDSLALGKSEEEALK 1009
Cdd:COG5032 2006 FRELCETAFRALRKNADSLMNVLELFVrdplieWRRLPCFReiQNNEIVNVLERFRLKLSEKDAEK 2071
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 5.35e-23

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 93.70  E-value: 5.35e-23
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 41055186      31 YLNFTVACSDTISTIKKMLWKNAKNEPLFSALSDPDAYVFTCINMTAEREELEDEQRRLCDVRPFLPILRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 313-400 2.29e-21

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 89.71  E-value: 2.29e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     313 NTCSLWSI--QEPFYIYLLQGSRVNADEGM-KLVVQAGLFHGSELLCKVVTSNEVSVCFDPVWDQKLVFDINVSDLPRMS 389
Cdd:smart00142    2 KIESLWDCdrNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREA 81

                            90
                    ....*....|.
gi 41055186     390 RLCFALYGVIE 400
Cdd:smart00142   82 RLCITIYAVKN 92
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 340-465 2.07e-20

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: 88.19  E-value: 2.07e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    340 MKLVVQAGLFHGSELLCKVVTSNEVSVCFD-PVWDQKLVFDINVSDLPRMSRLCFALYGViektkkrptkKKNKRADCPL 418
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV----------SGPEKSFVPI 72

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 41055186    419 AWVNTMVFDYKDQLKTGEFSLSTWPSVP---DDKGDLLNPMGTVEKNPNI 465
Cdd:pfam00792   73 GWVNTSLFDKKGILRQGKQKLRLWPSKStpgRSNVDEMNRLEKLLKKYER 122
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 188-280 1.09e-19

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: 85.04  E-value: 1.09e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    188 KIFVNVKFEGSEETFVLQQDPQDLPVVLKRNALRKKSTVFRSVKQEKpeDYSLQVNERWEFIYGKYPLCQFKYIFTCLHG 267
Cdd:pfam00794   16 KLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEYIRNCLKS 93

                           90
                   ....*....|...
gi 41055186    268 GLTPHLTMVHYSS 280
Cdd:pfam00794   94 GREPHLTLVEQSS 106
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 188-280 1.71e-10

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: 58.88  E-value: 1.71e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     188 KIFVNVKFEGSEETFVLQQDPQDLPVVLKRNALRKKSTVFRSVKQEKpEDYSLQVNERWEFIYGKYPLCQFKYIFTCLHG 267
Cdd:smart00144   17 KILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTS-EDYILKVCGRDEYLLGDHPLGSFEYIRNCLKN 95

                            90
                    ....*....|...
gi 41055186     268 GLTPHLTMVHYSS 280
Cdd:smart00144   96 GTEPHLVLMTLSA 108
ligD PRK09633
DNA ligase D;
933-1029 3.52e-03

DNA ligase D;


Pssm-ID: 182006 [Multi-domain]  Cd Length: 610  Bit Score: 41.18  E-value: 3.52e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186   933 DFVHVIQEGRTNNSEKFER---FRVCCEQAYKILCRNGTLFVN---------LFALMKAAGLPELN------------SS 988
Cdd:PRK09633   88 DFEHVQQRGRLKNTEVIAKsanARPCQLLAFDLLELKGESLTSlpylerkkqLDKLMKAAKLPASPdpyakariqyipST 167

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 41055186   989 KDIQYLKDSLALGKSEEEALKNFKVKFNEALRES-WKTKVNW 1029
Cdd:PRK09633  168 TDFDALWEAVKRYDGEGIVAKKKTSKWLENKRSKdWLKIKNW 209
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 676-1038 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: 786.55  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  676 IFHIKSLMKQNEALNKMKALNDFVKSASQKATRIQTTEDMKVCIKQETYMEALSDVVSPLSPSIILCELCADKCKFMDSK 755
Cdd:cd05174    1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  756 MKPLWLMYKSKY---DSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIAN 832
Cdd:cd05174   81 MKPLWIMYSSEEagaGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIAN 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  833 IQRNNSNSAATAAFNKDALLNWLKSKNPGDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 912
Cdd:cd05174  161 IQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  913 GNFKSKFGINRERVPFILTYDFVHVIQEGRTNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKDIQ 992
Cdd:cd05174  241 GNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQ 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 41055186  993 YLKDSLALGKSEEEALKNFKVKFNEALRESWKTKVNWMMHTFAKDN 1038
Cdd:cd05174  321 YLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 679-1036 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: 617.34  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  679 IKSLMKQNEALNKMKALNDFVKSasQKATRIQTTEDMKVCIKQETYMEALSDVVSPLSPSIILCELCADKCKFMDSKMKP 758
Cdd:cd05165    1 LKSLSRQVEALNKLKKLSDILKE--KKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  759 LWLMYKS------KYDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIAN 832
Cdd:cd05165   79 LWLVFENadplalSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  833 IQRNNSNSAaTAAFNKDALLNWLKSKNP-GDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 911
Cdd:cd05165  159 IQKKKGKVA-TLAFNKDSLHKWLKEKNKtGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHF 237

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  912 LGNFKSKFGINRERVPFILTYDFVHVIQEGRTN-NSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKD 990
Cdd:cd05165  238 LGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKD 317

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 41055186  991 IQYLKDSLALGKSEEEALKNFKVKFNEALRESWKTKVNWMMHTFAK 1036
Cdd:cd05165  318 IEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 679-1037 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: 603.49  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  679 IKSLMKQNEALNKMKALNDFVKSASQKATRIQTTEDMKVCIKQETYMEALSDVVSPLSPSIILCELCADKCKFMDSKMKP 758
Cdd:cd05173    1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  759 LWLMYKSKY---DSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQR 835
Cdd:cd05173   81 LWIVYNNKLfggDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  836 NNSNSAATAAFNKDALLNWLKSKNPGDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNF 915
Cdd:cd05173  161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  916 KSKFGINRERVPFILTYDFVHVIQEGRTNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKDIQYLK 995
Cdd:cd05173  241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|..
gi 41055186  996 DSLALGKSEEEALKNFKVKFNEALRESWKTKVNWMMHTFAKD 1037
Cdd:cd05173  321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 680-1020 3.34e-152

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: 455.11  E-value: 3.34e-152
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  680 KSLMKQNEALNKMKALNDFVKSASQkatriqtTEDMKVCIKQETYMEALSDVVSPLSPSIILCELCADKCKFMDSKMKPL 759
Cdd:cd00891    2 EELLKQVKVLDELKEIAKKIKEEPS-------EERKEVLEKLLQKLELPKKFTLPLDPRMEVKGLIVEKCKVMDSKKLPL 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  760 WLMYKSK---YDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQRn 836
Cdd:cd00891   75 WLVFKNAdpgGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQK- 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  837 nSNSAATAAFNKDALLNWLKSKNPGD-KLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNF 915
Cdd:cd00891  154 -KYGGFGAAFKDTPISNWLKKHNPTEeEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGNF 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  916 KSKFGINRERVPFILTYDFVHVIQEGrtnNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKDIQYLK 995
Cdd:cd00891  233 KKKFGIKRERAPFVFTPEMAYVMGGE---DSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYLR 309

                        330       340
                 ....*....|....*....|....*
gi 41055186  996 DSLALGKSEEEALKNFKVKFNEALR 1020
Cdd:cd00891  310 DALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 680-1035 1.22e-112

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: 352.36  E-value: 1.22e-112
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  680 KSLMKQNEALNKMKALNDFVKSASQKAtriqttedMKVCIKQEtyMEALSDVVS------PLSPSIILCELCADKCKFMD 753
Cdd:cd05166    2 EEFLKQHVLVQALTSIAEKVKSAKDSA--------RENALRRE--LEQLASFLLensfrlPLDPALEVTGVDVRSCSYFN 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  754 SKMKPLWLMYKS---KYDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTI 830
Cdd:cd05166   72 SNALPLKLVFRNadpRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETL 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  831 ANIQrnnSNSAATAAFNKDALLNWLKSKNPgDKLD--QAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDF 908
Cdd:cd05166  152 REIQ---TEHGLTGSFKDRPLADWLQKHNP-SELEyeKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDF 227

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  909 GHFLGNFKSKFGINRERVPFILTYDFVHVIQEGRtNNSEKFERF-RVCCeQAYKILCRNGTLFVNLFALMKAAGLPELNS 987
Cdd:cd05166  228 GKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGD-KPSSRFQLFvDLCC-QAFNIIRKNSNLLLNLLSLMLSSGIPGVTQ 305

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*...
gi 41055186  988 SkDIQYLKDSLALGKSEEEALKNFKVKFNEALReSWKTKVNWMMHTFA 1035
Cdd:cd05166  306 D-DLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNLA 351
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 734-1032 4.13e-109

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: 343.77  E-value: 4.13e-109
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  734 PLSPSIILCELCADKCKFMDSKMKPLWLMYKS------KYDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQ 807
Cdd:cd00894   58 PYDPGLRAGALVIEKCKVMASKKKPLWLEFKCadptalSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  808 PYGCLSTGNKTGLIEVVKNSDTIANIQRnnSNSAATAAFNKDALLNWLKSKNP-GDKLDQAIEEFTLSCAGYCVATYVLG 886
Cdd:cd00894  138 PYGCISTGDKIGMIEIVKDATTIAKIQQ--STVGNTGAFKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCVATFVLG 215

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  887 IGDRHSDNIMIRESGQLFHIDFGHFLGNFKSKFGINRERVPFILTYDFVHVIQEGRTNNSEKFERFRVCCEQAYKILCRN 966
Cdd:cd00894  216 IGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHH 295

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 41055186  967 GTLFVNLFALMKAAGLPELNSSKDIQYLKDSLALGKSEEEALKNFKVKFNEALRESWKTKVNWMMH 1032
Cdd:cd00894  296 TNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLH 361
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 678-1036 6.02e-106

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: 335.49  E-value: 6.02e-106
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  678 HIKSLMKQNEALNKMKALNDFVKSASQKATRIQTTEDMKVCIKQETYMEALSDVVSPLSPSIILCELCADKCKFMDSKMK 757
Cdd:cd05175    4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  758 PLWLMYKSK-------YDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTI 830
Cdd:cd05175   84 PLWLNWENPdimsellFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  831 ANIQRNNSNSAATAaFNKDALLNWLKSKNPGDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 910
Cdd:cd05175  164 MQIQCKGGLKGALQ-FNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 242

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  911 FLGNFKSKFGINRERVPFILTYDFVHVIQEG--RTNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSS 988
Cdd:cd05175  243 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 322

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*...
gi 41055186  989 KDIQYLKDSLALGKSEEEALKNFKVKFNEALRESWKTKVNWMMHTFAK 1036
Cdd:cd05175  323 DDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 505-676 2.83e-94

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: 296.53  E-value: 2.83e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  505 KEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRLKyPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELLD 584
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKK-PQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  585 YSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLRF 664
Cdd:cd00872   80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                        170
                 ....*....|..
gi 41055186  665 GLILEAYCRGSI 676
Cdd:cd00872  160 GLLLEAYLRGCG 171
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 734-1036 1.86e-80

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: 266.46  E-value: 1.86e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  734 PLSPSIILCELCADKCKFMDSKMKPLWLMYKSKyDSVG----IIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPY 809
Cdd:cd05176   52 PLSPSLVAKELNIKACSFFSSNAVPLKVALVNA-DPLGeeinVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIF 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  810 GCLSTGNKTGLIEVVKNSDTIANIQrnnSNSAATAAFNKDALLNWLKSKNPG-DKLDQAIEEFTLSCAGYCVATYVLGIG 888
Cdd:cd05176  131 KCLSTGKDRGMVELVPSSDTLRKIQ---VEYGVTGSFKDKPLAEWLRKYNPSeEEYEKASENFIYSCAGCCVATYVLGIC 207

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  889 DRHSDNIMIRESGQLFHIDFGHFLGNFKSKFGINRERVPFILTYDFVHVIQEGRTNNSeKFERFRVCCEQAYKILCRNGT 968
Cdd:cd05176  208 DRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEKPTI-RFQLFVDLCCQAYNLIRKHTN 286

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 41055186  969 LFVNLFALMKAAGLPELNSSKDIQYLKDSLALGKSEEEALKNFkVKFNEALRESWKTKVNWMMHTFAK 1036
Cdd:cd05176  287 LFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQTTDAEATIFF-TRLIESSLGSVATKFNFFIHNLAQ 353
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 315-481 2.40e-79

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: 256.08  E-value: 2.40e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  315 CSLWSIQEPFYIYLLQGSRVNA-DEGMKLVVQAGLFHGSELLCKVVTSNEVSVCFDPVWDQKLVFDINVSDLPRMSRLCF 393
Cdd:cd08693    1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  394 ALYGVIE-----KTKKRPTKKKNKRADCPLAWVNTMVFDYKDQLKTGEFSLSTWPSVPDDKGDLLNPMGTVEKNPNIDST 468
Cdd:cd08693   81 AIYEVSKkakgkRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                        170
                 ....*....|...
gi 41055186  469 AGLLIRFPNIRPH 481
Cdd:cd08693  161 TALHISFPEYKPE 173
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 772-989 1.65e-78

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: 256.46  E-value: 1.65e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     772 IIFKNGDDLRQDMLTLQMIQIMDILWKTE----GLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQRNN---------- 837
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     838 ------------SNSAATAAFNKDALLNWLKSKNPGDKLD--QAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 903
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     904 FHIDFGHFLGNFKSKFGiNRERVPFILTYDFVHVIqegrtNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLP 983
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 41055186     984 ELNSSK 989
Cdd:smart00146  235 DWRSGK 240
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 680-1035 1.46e-77

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: 258.23  E-value: 1.46e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  680 KSLMKQNEALNKMKALNDFVKSasQKATRIQTTEDMKVCIKQETYMEALSD--VVSPLSPSIILCELCADKCKFMDSKMK 757
Cdd:cd00896    2 EALKRQQEFVDRLRSLMKEVKN--EKGSRDKKIERLRELLSDSELGLLLFFepLPLPLDPSVKVTGIIPEKSTVFKSALM 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  758 PLWLMYK----SKYdsvGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANI 833
Cdd:cd00896   80 PLKLTFKtldgGEY---KVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  834 QRNNsnsaataafnkDALLNWLKSKNPGDK-----LDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDF 908
Cdd:cd00896  157 LKKY-----------GSILNFLRKHNPDESgpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDF 225

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  909 GHFLGN----FKSKFGINRERVPFIltydfvhviqeGRTnNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPE 984
Cdd:cd00896  226 GYILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPD 293

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|...
gi 41055186  985 LNSSKD--IQYLKDSLALGKSEEEALKNFKVKFNEALRESWkTKVNWMMHTFA 1035
Cdd:cd00896  294 IALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESVNALF-PAVVETIHKIA 345
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 698-1036 7.76e-77

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: 256.36  E-value: 7.76e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  698 FVKSASQKATRIQTTEDM--KVCIKQET--YMEALSDVVS---PLSPSIILCELCADKCKFMDSKMKPLWLMY---KSKY 767
Cdd:cd05177   10 LISILIDAAEKVKTASDTrrKEVLKREAsrLEDFFQDVVScclPLNPALRVKGIDADACSYFTSNAAPLKISFinaNPLA 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  768 DSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQRNnsnSAATAAFN 847
Cdd:cd05177   90 KNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRE---SGLIGPLK 166

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  848 KDALLNWLKSKNP-GDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKSKFGINRERV 926
Cdd:cd05177  167 ENTIEKWFHMHNKlKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSIKRDRA 246

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  927 PFILTYDFVHVIQEGrTNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKDIQYLKDSLALGKSEEE 1006
Cdd:cd05177  247 PFIFTSEMEYFITEG-GKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQDTDLE 325

                        330       340       350
                 ....*....|....*....|....*....|
gi 41055186 1007 ALKNFKVKFNEALrESWKTKVNWMMHTFAK 1036
Cdd:cd05177  326 ATSYFTKKIKESL-ECFPVKLNNLIHTLAQ 354
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 734-1036 8.81e-73

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: 245.30  E-value: 8.81e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  734 PLSPSIILCELCADKCKFMDSKMKPLWLMYKSK---YDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYG 810
Cdd:cd00895   53 PLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVdplGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFR 132

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  811 CLSTGNKTGLIEVVKNSDTIANIQRNNsnsAATAAFNKDALLNWLKSKNPG-DKLDQAIEEFTLSCAGYCVATYVLGIGD 889
Cdd:cd00895  133 CFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPTeDEYEKAVENFIYSCAGCCVATYVLGICD 209

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  890 RHSDNIMIRESGQLFHIDFGHFLGNFKSKFGINRERVPFILTYDFVHVIQEGrTNNSEKFERFRVCCEQAYKILCRNGTL 969
Cdd:cd00895  210 RHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGG-DKPSSRFHDFVDLCCQAYNLIRKHTHL 288

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 41055186  970 FVNLFALMKAAGLPELNSSKDIQYLKDSLALGKSEEEALKNFkVKFNEALRESWKTKVNWMMHTFAK 1036
Cdd:cd00895  289 FLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYF-TRLIESSLGSVATKLNFFIHNLAQ 354
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 769-987 3.80e-72

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: 239.15  E-value: 3.80e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    769 SVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDL-RMQPYGCLSTGNKTGLIEVVKNSDTIANIQRN--NSNSAATAA 845
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    846 FN-----------------------KDALLNWLKSKNPG-DKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RES 900
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    901 GQLFHIDFGHFLGNFKSKFGINrERVPFILTYDFVHVIqegrtNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAA 980
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*..
gi 41055186    981 GLPELNS 987
Cdd:pfam00454  235 GLPDWSI 241
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-684 1.25e-71

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: 235.61  E-value: 1.25e-71
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     504 TKEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRLKYPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELL 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     584 DYSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLR 663
Cdd:smart00145   84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIR 163

                           170       180
                    ....*....|....*....|.
gi 41055186     664 FGLILEAYCRGSIFHIKSLMK 684
Cdd:smart00145  164 FGLLLEAYLRGCGTHLKELLK 184
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-684 5.28e-60

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: 203.33  E-value: 5.28e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    504 TKEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRLKyPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELL 583
Cdd:pfam00613    6 NEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLV-PKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    584 DYSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLR 663
Cdd:pfam00613   85 DPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPR 164

                          170       180
                   ....*....|....*....|.
gi 41055186    664 FGLILEAYCRGSIFHIKSLMK 684
Cdd:pfam00613  165 FGSLLELYLRSCGTSLLGLNK 185
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 505-656 1.16e-59

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: 200.90  E-value: 1.16e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  505 KEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELrLKYPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELLD 584
Cdd:cd00864    1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYL-LNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLS 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 41055186  585 YSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMH 656
Cdd:cd00864   80 PKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 770-1026 1.47e-47

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: 171.68  E-value: 1.47e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  770 VGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQRNnsnsaaTAAFNKD 849
Cdd:cd00893   28 VSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKK------LDSFNKF 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  850 -ALLNWLKSKNPGDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKSKFGInrERVPF 928
Cdd:cd00893  102 vSLSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPF 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  929 ILTYDFVHVIqeGRTnNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELNSSKDIQYLKDSLALGKSEEEaL 1008
Cdd:cd00893  180 KLSSEYIEVL--GGV-DSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGE-L 255

                        250
                 ....*....|....*...
gi 41055186 1009 KNFKVKFNEALRESWKTK 1026
Cdd:cd00893  256 EVYVLSLINKSLDNWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 767-1006 8.54e-46

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: 166.50  E-value: 8.54e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  767 YDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQRNNSNSaataaf 846
Cdd:cd05168   28 WDLRSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNF------ 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  847 nkDALLNWLKSK---NPGDKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKSKFGInr 923
Cdd:cd05168  102 --TSLLDYFERTfgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF-- 177

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  924 ERVPFILTYDFVHVIqEGRtnNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAG-LPEL--NSSKDIQYLKDSLAL 1000
Cdd:cd05168  178 ETAPFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFfgGGEFTIEQLRERFKL 254


                 ....*.
gi 41055186 1001 GKSEEE 1006
Cdd:cd05168  255 NLTEEE 260
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 773-1026 1.91e-44

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: 163.15  E-value: 1.91e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  773 IFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIQRNNSNSaataafnkdaLL 852
Cdd:cd05167   53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQIGRETDNG----------LY 122

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  853 NWLKSKNpGDK----LDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGhFLgnFKSKFG--INRERV 926
Cdd:cd05167  123 EYFLSKY-GDEstpaFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FI--FEISPGgnLGFESA 198

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  927 PFILTYDFVHVIqeGRTNNSEKFERFRVCCEQAYKILCRNGTLFVNLFALMKAAGLPELnSSKDIQYLKDSLALGKSEEE 1006
Cdd:cd05167  199 PFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCF-RGQTIKNLRERFALEMSERE 275

                        250       260
                 ....*....|....*....|
gi 41055186 1007 ALKNFKVKFNEALrESWKTK 1026
Cdd:cd05167  276 AANFMIKLIADSY-LKIRTK 294
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 743-977 1.68e-42

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: 154.41  E-value: 1.68e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  743 ELCADKCKFMDSKMKPLWLMYKskyDSVG----IIFKNGDDLRQDMLTLQMIQIMDILWKTEGLDLRMQPYGCLSTGNKT 818
Cdd:cd00142    2 ALDVGILKVIHSKQRPKKITLI---GADGktysFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  819 GLIEVVKNSDTIANiqrnnsnsaataafnkdaLLNWLKSKNPG-DKLDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI 897
Cdd:cd00142   79 GLIEIVKDAQTIED------------------LLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMI 140

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  898 RESGQLFHIDFGHFLGNFKSKFGInrERVPFILTYDFVHVIQEGRTNNsekfeRFRVCCEQAYKILCRNGTLFVNLFALM 977
Cdd:cd00142  141 EPSGNIFHIDFGFIFSGRKLAEGV--ETVPFRLTPMLENAMGTAGVNG-----PFQISMVKIMEILREHADLIVPILEHS 213
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 315-479 2.39e-38

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: 140.19  E-value: 2.39e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  315 CSLWSIQEPFYIYLLQGSRVNADEG--MKLVVQAGLFHGSELLCKVVTSNEVSVCFDPVWDQKLVFDINVSDLPRMSRLC 392
Cdd:cd08380    1 KSLWDINFNLRIKIHGITNINLLDSedLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  393 FALYGVIEKTKKRptkkknkraDCPLAWVNTMVFDYKDQLKTGEFSLSTWPSVPDDkgdllNPMGTVEKNPNIDSTAGLL 472
Cdd:cd08380   81 LSIYAVSEPGSKK---------EVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPCNNSNENSTRLL 146


                 ....*..
gi 41055186  473 IRFPNIR 479
Cdd:cd08380  147 IELPEFS 153
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.23e-34

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 126.48  E-value: 1.23e-34
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 41055186     34 FTVACSDTISTIKKMLWKNAKNEPLFSALSDPDAYVFTCINMTAEREELEDEQRRLCDVRPFLPILRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
597-1009 6.94e-34

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 141.84  E-value: 6.94e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  597 IRCLRKLPDDKLFQYLLQLVQVLKYESyldcdltsFLLERALANKKIGHFLFWHL-RSEMHVPSVSLRFGLILEAYCRgs 675
Cdd:COG5032 1628 IRIAYPLLHLLFEPILAQLLSRLSSEN--------NKISVALLIDKPLHEERENFpSGLSLSSFQSSFLKELIKKSPR-- 1697

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  676 ifHIKSLMKQNEALNK--MKALNDFVKSASQKATRIQTTEDMKVCIKQETYMEALSDVV----SPLSPSIILCELCADKC 749
Cdd:COG5032 1698 --KIRKKFKIDISLLNlsRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFHAFLEIKLpgqyLLDKPFVLIERFEPEVS 1775

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  750 KFMDSKMKPLWLMYK-SKYDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTEGL----DLRMQPYGCLSTGNKTGLIEVV 824
Cdd:COG5032 1776 VVKSHLQRPRRLTIRgSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWV 1855

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  825 KNSDTIANI------QRNNSNSAAT---------------------AAFNKDALLNWLKSKNPGD-KLDQAIEEFTLSCA 876
Cdd:COG5032 1856 PNSDTLHSIlreyhkRKNISIDQEKklaarldnlklllkdefftkaTLKSPPVLYDWFSESFPNPeDWLTARTNFARSLA 1935

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  877 GYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKSKFGINrERVPFILTYDFVHVI----QEGrtnnsekfeR 951
Cdd:COG5032 1936 VYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMgvsgVEG---------S 2005

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 41055186  952 FRVCCEQAYKILCRNGTLFVNLFALMK------AAGLPELN--SSKDIQYLKDSLALGKSEEEALK 1009
Cdd:COG5032 2006 FRELCETAFRALRKNADSLMNVLELFVrdplieWRRLPCFReiQNNEIVNVLERFRLKLSEKDAEK 2071
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 315-467 4.81e-31

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: 119.51  E-value: 4.81e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  315 CSLWSIQEPFYIYLLQGSRVNADEGMKLVVQAGLFHGSELLCKVVTSNEVSvCFDPVWDQKLVFDINVSDLPRMSRLCFA 394
Cdd:cd08398    1 KSLWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLCDNVNTQRVP-CSNPRWNEWLDYDIYIPDLPRSARLCLS 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 41055186  395 LYGViektkkrPTKKKNKRADCPLAWVNTMVFDYKDQLKTGEFSLSTWPsVPDDKGDLLNPMGTVEKNPNIDS 467
Cdd:cd08398   80 ICSV-------KGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWP-VPHGLEDLLNPIGVTGSNPNKDT 144
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 505-670 8.39e-28

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: 110.62  E-value: 8.39e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  505 KEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELrLKYPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELLD 584
Cdd:cd00869    1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYC-TNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  585 YSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESYLDCDLTSFLLERALANKKIGHFLFWHLRSEMHVPSVSLRF 664
Cdd:cd00869   80 PKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAY 159


                 ....*.
gi 41055186  665 GLILEA 670
Cdd:cd00869  160 QDLGAA 165
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 504-656 3.38e-27

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: 108.96  E-value: 3.38e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  504 TKEEHQKLKEIVDNKNSTEFFEDEKEPLWKLREELRlKYPESLPKLLLITKWNKHEDVAQMVGLLQKWPELPALHALELL 583
Cdd:cd00870    7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLT-NNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELL 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  584 DYSFPDPHVRFFTIRCLRKLPDDKLFQYLLQLVQVLKYESY-------LDCDLTSFLLERALANKKIGHFLFWHLRSEMH 656
Cdd:cd00870   86 SPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWYLKVELE 165
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 5.35e-23

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 93.70  E-value: 5.35e-23
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 41055186      31 YLNFTVACSDTISTIKKMLWKNAKNEPLFSALSDPDAYVFTCINMTAEREELEDEQRRLCDVRPFLPILRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 773-979 2.49e-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: 96.57  E-value: 2.49e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  773 IFKNGDDLRQDMLTLQMIQIMD-ILWK---TEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANIqrnnsnsaataaFNK 848
Cdd:cd05164   33 LVKGDDDLRKDERVMQLFQLLNtLLEKdkeTRKRNLTIRTYSVVPLSSQSGLIEWVDNTTTLKPV------------LKK 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  849 DAllnWLKSKNPGDKLDqAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGnfKSKFGINRERVP 927
Cdd:cd05164  101 WF---NETFPDPTQWYE-ARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFN--KGKTLPVPEIVP 174

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 41055186  928 FILTYDFVHVIQEGRTNNSekferFRVCCEQAYKILCRNGTLfvnLFALMKA 979
Cdd:cd05164  175 FRLTRNIINGMGPTGVEGL-----FRKSCEQVLRVFRKHKDK---LITFLDT 218
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 313-400 2.29e-21

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 89.71  E-value: 2.29e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     313 NTCSLWSI--QEPFYIYLLQGSRVNADEGM-KLVVQAGLFHGSELLCKVVTSNEVSVCFDPVWDQKLVFDINVSDLPRMS 389
Cdd:smart00142    2 KIESLWDCdrNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREA 81

                            90
                    ....*....|.
gi 41055186     390 RLCFALYGVIE 400
Cdd:smart00142   82 RLCITIYAVKN 92
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 340-465 2.07e-20

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: 88.19  E-value: 2.07e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    340 MKLVVQAGLFHGSELLCKVVTSNEVSVCFD-PVWDQKLVFDINVSDLPRMSRLCFALYGViektkkrptkKKNKRADCPL 418
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV----------SGPEKSFVPI 72

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 41055186    419 AWVNTMVFDYKDQLKTGEFSLSTWPSVP---DDKGDLLNPMGTVEKNPNI 465
Cdd:pfam00792   73 GWVNTSLFDKKGILRQGKQKLRLWPSKStpgRSNVDEMNRLEKLLKKYER 122
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 188-280 1.09e-19

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: 85.04  E-value: 1.09e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186    188 KIFVNVKFEGSEETFVLQQDPQDLPVVLKRNALRKKSTVFRSVKQEKpeDYSLQVNERWEFIYGKYPLCQFKYIFTCLHG 267
Cdd:pfam00794   16 KLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEYIRNCLKS 93

                           90
                   ....*....|...
gi 41055186    268 GLTPHLTMVHYSS 280
Cdd:pfam00794   94 GREPHLTLVEQSS 106
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 752-939 1.48e-19

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: 88.79  E-value: 1.48e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  752 MDSKMKPLWL-MYKSKYDSVGIIFKNGDDLRQDMLTLQMIQIMDILWKTE----GLDLRMQPYGCLSTGNKTGLIEVVKN 826
Cdd:cd05172   11 LSSKRRPKRItIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWVDN 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  827 SDTIANIQRNN-------SNSAATAAFnkdaLLnwLKSKnpgdkldqaieeFTLSCAGYCVATYVLGIGDRHSDNIMI-R 898
Cdd:cd05172   91 TTPLKEILENDllrrallSLASSPEAF----LA--LRSN------------FARSLAAMSICGYILGIGDRHLSNFLVdL 152

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 41055186  899 ESGQLFHIDFGHFLGNFKSKFGINrERVPFILTYDFVHVIQ 939
Cdd:cd05172  153 STGRLIGIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQ 192
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 767-966 3.02e-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: 89.14  E-value: 3.02e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  767 YDSVGI----IFKNGDDLRQDMLTLQMIQIMDILWK----TEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANI-QRNN 837
Cdd:cd05171   23 IGSDGKkykqLVKGGDDLRQDAVMEQVFELVNQLLKrdkeTRKRKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYlVGAS 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  838 SNSAATAAFN-KD-------ALLNWLKSKNPGDKLD----------------------------QAIEEFTLSCAGYCVA 881
Cdd:cd05171  103 SKSGAHARYRpKDwtastcrKKMREKAKASAEERLKvfdeicknfkpvfrhfflekfpdpsdwfERRLAYTRSVATSSIV 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  882 TYVLGIGDRHSDNIMI-RESGQLFHIDFG-HFlgnfksKFGIN---RERVPFILTYDFVH------ViqEGrtnnsekfe 950
Cdd:cd05171  183 GYILGLGDRHLNNILIdQKTGELVHIDLGiAF------EQGKLlpiPETVPFRLTRDIVDgmgitgV--EG--------- 245

                        250
                 ....*....|....*.
gi 41055186  951 RFRVCCEQAYKILCRN 966
Cdd:cd05171  246 VFRRCCEETLRVLREN 261
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 346-477 3.10e-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: 3.10e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  346 AGLFHGSELLCKVVTSNEVSVC--FDP--VWDQKLVFDINVSDLPRMSRLCFALYGVieKTKKRPTKKKNKRADCPLAWV 421
Cdd:cd04012   35 CSLYHGGRLLCSPVTTKPVKITksFFPrvVWDEWIEFPIPVCQLPRESRLVLTLYGT--TSSPDGGSNKQRMGPEELGWV 112

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 41055186  422 NTMVFDYKDQLKTGEFSLSTWPSVPDdkgdllNPMG-TVEKNPNIDSTAGLLIRFPN 477
Cdd:cd04012  113 SLPLFDFRGVLRQGSLLLGLWPPSKD------NPLGpAPPPLFEQPDRVILQIDFPS 163
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 775-967 4.97e-17

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: 82.53  E-value: 4.97e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  775 KNGDDLRQDMLTLQMIQIMDILWK----TEGLDLRMQPYGCLSTGNKTGLIEVVKNSDTIANI---QRNNSNSAATA--- 844
Cdd:cd05169   35 KGHEDLRLDERVMQLFGLVNTLLKndseTSRRNLSIQRYSVIPLSPNSGLIGWVPGCDTLHSLirdYREKRKIPLNIehr 114

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  845 -------------------AFN-----------KDALlnWLKSKNPGDKLDQAIEeFTLSCAGYCVATYVLGIGDRHSDN 894
Cdd:cd05169  115 lmlqmapdydnltliqkveVFEyalentpgddlRRVL--WLKSPSSEAWLERRTN-FTRSLAVMSMVGYILGLGDRHPSN 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  895 IMI-RESGQLFHIDFG-------HflgnfKSKFginRERVPFILTYDFVHVIQEGRTNNSekferFRVCCEQAYKILCRN 966
Cdd:cd05169  192 IMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRMLVNAMEVSGVEGT-----FRSTCEDVMRVLREN 258


                 .
gi 41055186  967 G 967
Cdd:cd05169  259 K 259
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 747-963 2.21e-13

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: 71.00  E-value: 2.21e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  747 DKCKFMDSKMKPLWLMYK-SKYDSVGIIFKNGDDLRQDMLTLQMIQIMDILWK----TEGLDLRMQPYGCLSTGNKTGLI 821
Cdd:cd00892    6 DEVEIMPSLQKPKKITLVgSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSkdpeSRRRNLHIRTYAVIPLNEECGII 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  822 EVVKNSDTIANIqrnnSNSAATAAFNKdallnWLKSK--NPGDKLdQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-R 898
Cdd:cd00892   86 EWVPNTVTLRSI----LSTLYPPVLHE-----WFLKNfpDPTAWY-EARNNYTRSTAVMSMVGYILGLGDRHGENILFdS 155

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 41055186  899 ESGQLFHIDF------GHflgnfksKFGInRERVPFILTYDFVHVI----QEGrtnnsekfeRFRVCCEQAYKIL 963
Cdd:cd00892  156 TTGDVVHVDFdclfdkGL-------TLEV-PERVPFRLTQNMVDAMgvtgVEG---------TFRRTCEVTLRVL 213
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-473 3.27e-11

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: 63.01  E-value: 3.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  314 TCSLWSIQEPFYIYLLQGS----RVNADegMKLVVQAGLFHGSELLCKVVTSNEvSVCFDPVWDQKLVFDINVSDLPRMS 389
Cdd:cd08399    2 TVSLWDCDRKFRVKILGIDipvlPRNTD--LTVFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGA 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  390 RLCFALYGVIEKTKKRPTKKKNKRADCP-----LAWVNTMVFDYKDQLKTGEFSLSTW--PSVPDDKGDLLNPMGTVEKN 462
Cdd:cd08399   79 LLNLQIYCGKAPALSSKKSAESPSSESKgkhqlLYYVNLLLIDHRFLLRTGEYVLHMWqiSGKGEDQGSVNADKLTSATN 158

                        170
                 ....*....|.
gi 41055186  463 PNIDSTAGLLI 473
Cdd:cd08399  159 PDKENSMSISI 169
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 188-280 1.71e-10

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: 58.88  E-value: 1.71e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186     188 KIFVNVKFEGSEETFVLQQDPQDLPVVLKRNALRKKSTVFRSVKQEKpEDYSLQVNERWEFIYGKYPLCQFKYIFTCLHG 267
Cdd:smart00144   17 KILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTS-EDYILKVCGRDEYLLGDHPLGSFEYIRNCLKN 95

                            90
                    ....*....|...
gi 41055186     268 GLTPHLTMVHYSS 280
Cdd:smart00144   96 GTEPHLVLMTLSA 108
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 854-966 1.16e-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: 60.73  E-value: 1.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  854 WLKSKNpgdkldqaieeFTLSCAGYCVATYVLGIGDRHSDNIMIR-ESGQLFHIDF------GHFLgnfkskfginR--E 924
Cdd:cd05170  188 WRVTQR-----------FARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpE 246

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 41055186  925 RVPFILTYDFVHVIQ----EGrtnnsekfeRFRVCCEQAYKILCRN 966
Cdd:cd05170  247 KVPFRLTQNIEHALGptgvEG---------TFRLSCEQVLKILRKG 283
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 757-909 3.28e-09

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: 56.30  E-value: 3.28e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  757 KPLWLMYKSKydSVGIIFKNGDDlRQDMLTLQMIQIMDILWKTEGLDLrmQPYGCLST----GNKTGLIEVVKNSDTIAN 832
Cdd:cd13968    8 KVFWAEGECT--TIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTedvdGPNILLMELVKGGTLIAY 82

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 41055186  833 IQRNNSNSAATAAFNKDallnwlksknpgdkldqaieeftlsCAGYCVATYV--LGIGDRHSDNIMIRESGQLFHIDFG 909
Cdd:cd13968   83 TQEEELDEKDVESIMYQ-------------------------LAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 540-655 5.53e-06

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: 47.74  E-value: 5.53e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  540 LKYPESLPklLLITKWNKHEDVAQMVGLLQkWPELPALHALELLDYSFP-DPHVRFFTIRCLRKLPDDKLFQYLLQLVQV 618
Cdd:cd00871   37 VKIPEALP--FLVTGKSVDENSPDLKYLLY-WAPVSPVQALSLFTPQYPgHPLVLQYAVRVLESYPVETVFFYIPQIVQA 113

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 41055186  619 LKYES--YLDcdltSFLLERALANKKIGHFLFWHLRSEM 655
Cdd:cd00871  114 LRYDKmgYVE----EYILETAKRSQLFAHQIIWNMQTNC 148
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 870-931 9.77e-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: 42.12  E-value: 9.77e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 41055186  870 EFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFgHF-LGNFKSKFGINRErVPFILT 931
Cdd:cd05163  140 QFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDF-LPsINSQGPLLDNNEP-VPFRLT 201
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 319-475 1.37e-03

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: 40.31  E-value: 1.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  319 SIQEPFYIYLLQGSRVNADegmkLVVQAGLFHGSELLC-KVVTSnevsvcFDP-----VWDQKLVFDINVSDLPRMSRLC 392
Cdd:cd08397   13 KLEDPVLRFSGSNVSPNSD----LFVTCQVFDDGKPLTlPVQTS------YKPfknrrNWNEWLTLPIKYSDLPRNSQLA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186  393 FALYGVIEKTKkrptkkknkraDCPLAWVNTMVFDYKDQLKTGEFSLSTWPSVPDDkGDLLNPMGTVEKNPN--IDSTAG 470
Cdd:cd08397   83 ITIWDVSGTGK-----------AVPFGGTTLSLFNKDGTLRRGRQKLRVWPDVEAD-GSIPTSTGKSPDSERdeLDRLEK 150


                 ....*
gi 41055186  471 LLIRF 475
Cdd:cd08397  151 LLKKY 155
ligD PRK09633
DNA ligase D;
933-1029 3.52e-03

DNA ligase D;


Pssm-ID: 182006 [Multi-domain]  Cd Length: 610  Bit Score: 41.18  E-value: 3.52e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41055186   933 DFVHVIQEGRTNNSEKFER---FRVCCEQAYKILCRNGTLFVN---------LFALMKAAGLPELN------------SS 988
Cdd:PRK09633   88 DFEHVQQRGRLKNTEVIAKsanARPCQLLAFDLLELKGESLTSlpylerkkqLDKLMKAAKLPASPdpyakariqyipST 167

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 41055186   989 KDIQYLKDSLALGKSEEEALKNFKVKFNEALRES-WKTKVNW 1029
Cdd:PRK09633  168 TDFDALWEAVKRYDGEGIVAKKKTSKWLENKRSKdWLKIKNW 209
 
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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