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Conserved domains on  [gi|1868156914|ref|XP_035295295|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [Cricetulus griseus]

Protein Classification

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

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

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 680-1046 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: 815.05  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  680 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSK 759
Cdd:cd05174      1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  760 MKPLWIMYSSEEAGsAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 839
Cdd:cd05174     81 MKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  840 NIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 919
Cdd:cd05174    160 NIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  920 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDI 999
Cdd:cd05174    240 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDI 319

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1868156914 1000 QYLKDSLALGKTEEEALKQFRVKFNEALRESWKTKVNWLAHNVSKDN 1046
Cdd:cd05174    320 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 9.33e-92

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


:

Pssm-ID: 176075  Cd Length: 173  Bit Score: 289.98  E-value: 9.33e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  314 VSLWSLEQPFCIELMEGSKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWRQRLEFDINICDLPRMARLCF 392
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  393 ALYAVVEKAKKARSTK----KKSRKADCPIAWANLMLFDYKDQLKTGERRLYMWPSVPDEKGELLNPAGTVRSNPNTESA 468
Cdd:cd08693     81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                          170
                   ....*....|...
gi 1868156914  469 AALVIFLPEVAPH 481
Cdd:cd08693    161 TALHISFPEYKPE 173
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 505-688 5.35e-82

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: 264.12  E-value: 5.35e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   505 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSAL 584
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQ---ALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   585 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSV 664
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1868156914   665 ALRFGLIMEAYCRGSTHHMKVLMK 688
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.07e-35

PI3-kinase family, p85-binding domain;


:

Pssm-ID: 460483  Cd Length: 74  Bit Score: 129.56  E-value: 1.07e-35
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1868156914   34 FPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 1.22e-33

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: 125.10  E-value: 1.22e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  182 ILRVTNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVEQpeDYALQVNGRHEYLYGNYPLCQFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 1868156914  262 ICSCLHSGLTPHLTMVHASS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 680-1046 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: 815.05  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  680 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSK 759
Cdd:cd05174      1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  760 MKPLWIMYSSEEAGsAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 839
Cdd:cd05174     81 MKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  840 NIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 919
Cdd:cd05174    160 NIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  920 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDI 999
Cdd:cd05174    240 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDI 319

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1868156914 1000 QYLKDSLALGKTEEEALKQFRVKFNEALRESWKTKVNWLAHNVSKDN 1046
Cdd:cd05174    320 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 9.33e-92

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


Pssm-ID: 176075  Cd Length: 173  Bit Score: 289.98  E-value: 9.33e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  314 VSLWSLEQPFCIELMEGSKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWRQRLEFDINICDLPRMARLCF 392
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  393 ALYAVVEKAKKARSTK----KKSRKADCPIAWANLMLFDYKDQLKTGERRLYMWPSVPDEKGELLNPAGTVRSNPNTESA 468
Cdd:cd08693     81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                          170
                   ....*....|...
gi 1868156914  469 AALVIFLPEVAPH 481
Cdd:cd08693    161 TALHISFPEYKPE 173
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 505-688 5.35e-82

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: 264.12  E-value: 5.35e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   505 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSAL 584
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQ---ALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   585 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSV 664
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1868156914   665 ALRFGLIMEAYCRGSTHHMKVLMK 688
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 780-997 1.90e-80

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


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 261.85  E-value: 1.90e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   780 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 844
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   845 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 911
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   912 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 991
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1868156914   992 ELSCSK 997
Cdd:smart00146  235 DWRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 777-994 2.96e-76

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


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 250.71  E-value: 2.96e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  777 SVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAA 853
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  854 FN-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RES 908
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  909 GQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAA 988
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*.
gi 1868156914  989 GLPELS 994
Cdd:pfam00454  235 GLPDWS 240
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 506-679 2.75e-74

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: 242.60  E-value: 2.75e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  506 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSALE 585
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQ---MYQLLKRWPKLKPEQALE 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  586 LLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSVA 665
Cdd:cd00872     77 LLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVS 156

                          170
                   ....*....|....
gi 1868156914  666 LRFGLIMEAYCRGS 679
Cdd:cd00872    157 QRFGLLLEAYLRGC 170
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 503-688 2.94e-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: 204.10  E-value: 2.94e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  503 RITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLS 582
Cdd:pfam00613    4 KPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAE---ALSLLLKWAPIDPVD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  583 ALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVP 662
Cdd:pfam00613   80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 1868156914  663 SVALRFGLIMEAYCRGSTHHMKVLMK 688
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
638-1019 1.90e-36

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 150.32  E-value: 1.90e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  638 LDRALANRKIGHFLFWHL-RSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMKqgeaLSKLKALNDFVKVSSQKTTKPQTK 716
Cdd:COG5032   1657 ISVALLIDKPLHEERENFpSGLSLSSFQSSFLKELIKKSPRKIRKKFKIDIS----LLNLSRKLYISVLRSIRKRLKRLL 1732

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  717 EMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCVEQCTFMDSKMKPLWIMYSseeaGSAGSV-GIIFKNGDDLR 789
Cdd:COG5032   1733 ELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEPEVSVVKSHLQRPRRLTIR----GSDGKLySFIVKGGDDLR 1808

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  790 QDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANI------QLNKS-NMAATAAFNKDA 858
Cdd:COG5032   1809 QDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDN 1888

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  859 LLNWLKSKNPGEALD---------------------RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDF 916
Cdd:COG5032   1889 LKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFARSLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDF 1968

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  917 GHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPE---L 993
Cdd:COG5032   1969 GFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEwrrL 2042

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1868156914  994 SCSKDIQY-----LKDSLALGKTEEEALKQF 1019
Cdd:COG5032   2043 PCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.07e-35

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 129.56  E-value: 1.07e-35
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1868156914   34 FPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 1.22e-33

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: 125.10  E-value: 1.22e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  182 ILRVTNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVEQpeDYALQVNGRHEYLYGNYPLCQFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 1868156914  262 ICSCLHSGLTPHLTMVHASS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 312-407 3.71e-30

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 114.75  E-value: 3.71e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   312 SSVSLWSLEQPFCIELMEGSKVNADERM-KLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWRQRLEFDINICDLPRMARL 390
Cdd:smart00142    4 ESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARL 83

                            90
                    ....*....|....*..
gi 1868156914   391 CFALYAVVEKAKKARST 407
Cdd:smart00142   84 CITIYAVKNPSKGSEFG 100
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 339-448 2.43e-22

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


Pssm-ID: 395640  Cd Length: 136  Bit Score: 93.97  E-value: 2.43e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  339 MKLVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWRQRLEFDINICDLPRMARLCFALYAVvekakkarstkKKSRKADCP 417
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVP 71

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1868156914  418 IAWANLMLFDYKDQLKTGERRLYMWPSVPDE 448
Cdd:pfam00792   72 IGWVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 4.31e-21

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 88.31  E-value: 4.31e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1868156914    31 YLNFPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 183-277 5.51e-18

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: 80.45  E-value: 5.51e-18
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   183 LRVTNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPlVEQPEDYALQVNGRHEYLYGNYPLCQFQYI 262
Cdd:smart00144   11 LKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQV-DPTSEDYILKVCGRDEYLLGDHPLGSFEYI 89

                            90
                    ....*....|....*
gi 1868156914   263 CSCLHSGLTPHLTMV 277
Cdd:smart00144   90 RNCLKNGTEPHLVLM 104
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 680-1046 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: 815.05  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  680 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSK 759
Cdd:cd05174      1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  760 MKPLWIMYSSEEAGsAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 839
Cdd:cd05174     81 MKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  840 NIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 919
Cdd:cd05174    160 NIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  920 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDI 999
Cdd:cd05174    240 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDI 319

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1868156914 1000 QYLKDSLALGKTEEEALKQFRVKFNEALRESWKTKVNWLAHNVSKDN 1046
Cdd:cd05174    320 QYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 683-1044 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: 655.86  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  683 MKVLMKQGEALSKLKALNDFVKVssQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMKP 762
Cdd:cd05165      1 LKSLSRQVEALNKLKKLSDILKE--KKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  763 LWIMYSSEE--AGSAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIAN 840
Cdd:cd05165     79 LWLVFENADplALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  841 IQLNKSNMAaTAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHF 919
Cdd:cd05165    159 IQKKKGKVA-TLAFNKDSLHKWLKEKNKtGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHF 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  920 LGNFKTKFGINRERVPFILTYDFVHVIQQGKTN-NSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 998
Cdd:cd05165    238 LGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKD 317

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 1868156914  999 IQYLKDSLALGKTEEEALKQFRVKFNEALRESWKTKVNWLAHNVSK 1044
Cdd:cd05165    318 IEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 683-1045 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: 630.84  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  683 MKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMKP 762
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  763 LWIMYSSEEAGSaGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQ 842
Cdd:cd05173     81 LWIVYNNKLFGG-DSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQ 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  843 LNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGN 922
Cdd:cd05173    160 LNSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGN 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  923 FKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYL 1002
Cdd:cd05173    240 FKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYL 319

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|...
gi 1868156914 1003 KDSLALGKTEEEALKQFRVKFNEALRESWKTKVNWLAHNVSKD 1045
Cdd:cd05173    320 KDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 683-1028 2.55e-148

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: 445.09  E-value: 2.55e-148
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  683 MKVLMKQGEALSKLKALNDFVK-VSSQKttkpqtkemmhmcmRQETYMEALSHLQS------PLDPSTLLEEVCVEQCTF 755
Cdd:cd00891      1 REELLKQVKVLDELKEIAKKIKeEPSEE--------------RKEVLEKLLQKLELpkkftlPLDPRMEVKGLIVEKCKV 66

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  756 MDSKMKPLWIMYSSEEAGsAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHS 835
Cdd:cd00891     67 MDSKKLPLWLVFKNADPG-GDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNS 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  836 DTIANIQlnKSNMAATAAFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHI 914
Cdd:cd00891    146 ETTAAIQ--KKYGGFGAAFKDTPISNWLKKHNPTEEeYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHI 223

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  915 DFGHFLGNFKTKFGINRERVPFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELS 994
Cdd:cd00891    224 DFGHFLGNFKKKFGIKRERAPFVFTPEMAYVM-GGE--DSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQ 300

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1868156914  995 CSKDIQYLKDSLALGKTEEEALKQFRVKFNEALR 1028
Cdd:cd00891    301 SIEDIEYLRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 686-1042 9.52e-117

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


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 363.53  E-value: 9.52e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  686 LMKQGEALSKLKALNDFVKvssqkttkpQTKEmmhmCMRQETYMEALSHLQS---------PLDPSTLLEEVCVEQCTFM 756
Cdd:cd05166      4 FLKQHVLVQALTSIAEKVK---------SAKD----SARENALRRELEQLASfllensfrlPLDPALEVTGVDVRSCSYF 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  757 DSKMKPLWIMYSSEEAGsAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSD 836
Cdd:cd05166     71 NSNALPLKLVFRNADPR-AEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAE 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  837 TIANIQlnkSNMAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHID 915
Cdd:cd05166    150 TLREIQ---TEHGLTGSFKDRPLADWLQKHNPSElEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHID 226

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  916 FGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSc 995
Cdd:cd05166    227 FGKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGD-KPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT- 304

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1868156914  996 SKDIQYLKDSLALGKTEEEALKQFRVKFNEALReSWKTKVNWLAHNV 1042
Cdd:cd05166    305 QDDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 682-1044 2.52e-108

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


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 342.04  E-value: 2.52e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  682 HMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMK 761
Cdd:cd05175      4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  762 PLWIMYSSEEAGSA---GSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 838
Cdd:cd05175     84 PLWLNWENPDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  839 ANIQLnKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 918
Cdd:cd05175    164 MQIQC-KGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  919 FLGNFKTKFGINRERVPFILTYDFVHVIQQG--KTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCS 996
Cdd:cd05175    243 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 322

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1868156914  997 KDIQYLKDSLALGKTEEEALKQFRVKFNEALRESWKTKVNWLAHNVSK 1044
Cdd:cd05175    323 DDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 733-1042 3.16e-106

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


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 336.07  E-value: 3.16e-106
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  733 SHLQSPLDPSTLLEEVCVEQCTFMDSKMKPLWIMYS--SEEAGSAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL 810
Cdd:cd00894     53 ESFRVPYDPGLRAGALVIEKCKVMASKKKPLWLEFKcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESL 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  811 DLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCVA 889
Cdd:cd00894    133 DLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCVA 210

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  890 TYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYT 969
Cdd:cd00894    211 TFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYL 290

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1868156914  970 ILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKQFRVKFNEALRESWKTKVNWLAHNV 1042
Cdd:cd00894    291 ALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 9.33e-92

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


Pssm-ID: 176075  Cd Length: 173  Bit Score: 289.98  E-value: 9.33e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  314 VSLWSLEQPFCIELMEGSKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWRQRLEFDINICDLPRMARLCF 392
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  393 ALYAVVEKAKKARSTK----KKSRKADCPIAWANLMLFDYKDQLKTGERRLYMWPSVPDEKGELLNPAGTVRSNPNTESA 468
Cdd:cd08693     81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                          170
                   ....*....|...
gi 1868156914  469 AALVIFLPEVAPH 481
Cdd:cd08693    161 TALHISFPEYKPE 173
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 724-1044 2.04e-85

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


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 279.94  E-value: 2.04e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  724 RQETYMEALSHLQS---------PLDPSTLLEEVCVEQCTFMDSKMKPLWI-MYSSEEAGSagSVGIIFKNGDDLRQDML 793
Cdd:cd05176     29 RQVALQDGMERVQSffqknkcrlPLSPSLVAKELNIKACSFFSSNAVPLKVaLVNADPLGE--EINVMFKVGEDLRQDML 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  794 TLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNksnMAATAAFNKDALLNWLKSKNPGE-AL 872
Cdd:cd05176    107 ALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVE---YGVTGSFKDKPLAEWLRKYNPSEeEY 183

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  873 DRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTN 952
Cdd:cd05176    184 EKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEKP 263

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  953 NSeKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEAlKQFRVKFNEALRESWK 1032
Cdd:cd05176    264 TI-RFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQTTDAEA-TIFFTRLIESSLGSVA 341

                          330
                   ....*....|..
gi 1868156914 1033 TKVNWLAHNVSK 1044
Cdd:cd05176    342 TKFNFFIHNLAQ 353
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 505-688 5.35e-82

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: 264.12  E-value: 5.35e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   505 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSAL 584
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQ---ALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   585 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSV 664
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1868156914   665 ALRFGLIMEAYCRGSTHHMKVLMK 688
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 780-997 1.90e-80

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


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 261.85  E-value: 1.90e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   780 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 844
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   845 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 911
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   912 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 991
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1868156914   992 ELSCSK 997
Cdd:smart00146  235 DWRSGK 240
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 684-1027 5.45e-79

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


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 262.08  E-value: 5.45e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  684 KVLMKQGEALSKLKALNDFVKVSSQKTTKpQTKEMMHMCMRQETYMEALSH-LQSPLDPSTLLEEVCVEQCTFMDSKMKP 762
Cdd:cd00896      2 EALKRQQEFVDRLRSLMKEVKNEKGSRDK-KIERLRELLSDSELGLLLFFEpLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  763 LWIMYSSEEAGSagsVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIq 842
Cdd:cd00896     81 LKLTFKTLDGGE---YKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  843 LNKSNmaataafnkdALLNWLKSKNPGEA-----LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFG 917
Cdd:cd00896    157 LKKYG----------SILNFLRKHNPDESgpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFG 226

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  918 HFLGN----FKTKFGINRERVPFIltydfvhviqqGKTnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPEL 993
Cdd:cd00896    227 YILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDI 294

                          330       340       350
                   ....*....|....*....|....*....|....*.
gi 1868156914  994 SCSKD--IQYLKDSLALGKTEEEALKQFRVKFNEAL 1027
Cdd:cd00896    295 ALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 684-1044 5.06e-78

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: 259.82  E-value: 5.06e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  684 KVLMKQGEALSKLKALNDFVKVSSqkttKPQTKEMMHMCMRQ-ETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMKP 762
Cdd:cd05177      2 KEFSKETKLISILIDAAEKVKTAS----DTRRKEVLKREASRlEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAP 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  763 LWIMYSSEEAgSAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQ 842
Cdd:cd05177     78 LKISFINANP-LAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIH 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  843 lNKSNMAATaaFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLG 921
Cdd:cd05177    157 -RESGLIGP--LKENTIEKWFHMHNKLKEdYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLG 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  922 NFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQY 1001
Cdd:cd05177    234 HAQTFGSIKRDRAPFIFTSEMEYFITEGG-KKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKY 312

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|...
gi 1868156914 1002 LKDSLALGKTEEEALKQFRVKFNEALrESWKTKVNWLAHNVSK 1044
Cdd:cd05177    313 VYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTLAQ 354
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 777-994 2.96e-76

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


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 250.71  E-value: 2.96e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  777 SVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAA 853
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  854 FN-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RES 908
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  909 GQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAA 988
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*.
gi 1868156914  989 GLPELS 994
Cdd:pfam00454  235 GLPDWS 240
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 738-1044 2.30e-74

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


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 249.92  E-value: 2.30e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  738 PLDPSTLLEEVCVEQCTFMDSKMKPLWIMYSSEEAgSAGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPY 817
Cdd:cd00895     53 PLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDP-LGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIF 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  818 GCLPTGDRTGLIEVVLHSDTIANIQLNKsnmAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGIG 896
Cdd:cd00895    132 RCFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPTEdEYEKAVENFIYSCAGCCVATYVLGIC 208

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  897 DRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHGL 976
Cdd:cd00895    209 DRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSS-RFHDFVDLCCQAYNLIRKHTH 287

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1868156914  977 LFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKQFrVKFNEALRESWKTKVNWLAHNVSK 1044
Cdd:cd00895    288 LFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYF-TRLIESSLGSVATKLNFFIHNLAQ 354
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 506-679 2.75e-74

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: 242.60  E-value: 2.75e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  506 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSALE 585
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQ---MYQLLKRWPKLKPEQALE 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  586 LLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSVA 665
Cdd:cd00872     77 LLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVS 156

                          170
                   ....*....|....
gi 1868156914  666 LRFGLIMEAYCRGS 679
Cdd:cd00872    157 QRFGLLLEAYLRGC 170
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 503-688 2.94e-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: 204.10  E-value: 2.94e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  503 RITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLS 582
Cdd:pfam00613    4 KPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAE---ALSLLLKWAPIDPVD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  583 ALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVP 662
Cdd:pfam00613   80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 1868156914  663 SVALRFGLIMEAYCRGSTHHMKVLMK 688
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 507-660 8.01e-51

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: 175.87  E-value: 8.01e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  507 EEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVaqlSQMLYLLCSWPELPVLSALEL 586
Cdd:cd00864      2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNV-PKALPKLLKSVNWNDDEEV---SELYQLLKWWAPLSPEDALEL 77

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1868156914  587 LDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMH 660
Cdd:cd00864     78 LSPKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 781-1034 1.16e-49

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


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 178.17  E-value: 1.16e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  781 IFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSdtianiqlnKS--NMAATAAFNkda 858
Cdd:cd05167     53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNS---------KSrdQIGRETDNG--- 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  859 LLNWLKSK--NPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGhFL------GNFKTkfgi 929
Cdd:cd05167    121 LYEYFLSKygDEStPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIfeispgGNLGF---- 195

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  930 nrERVPFILTYDFVHVIqqGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPelsC--SKDIQYLKDSLA 1007
Cdd:cd05167    196 --ESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLP---CfrGQTIKNLRERFA 268

                          250       260
                   ....*....|....*....|....*..
gi 1868156914 1008 LGKTEEEALKQFRVKFNEALrESWKTK 1034
Cdd:cd05167    269 LEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 778-1034 9.84e-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: 169.36  E-value: 9.84e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  778 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIAniQLNKSNMAATAAFNkd 857
Cdd:cd00893     28 VSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSID--SLKKKLDSFNKFVS-- 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  858 aLLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERVPFI 937
Cdd:cd00893    104 -LSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPFK 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  938 LTYDFVHVIqqgKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALK 1017
Cdd:cd00893    181 LSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEV 257

                          250
                   ....*....|....*..
gi 1868156914 1018 QFRVKFNEALReSWKTK 1034
Cdd:cd00893    258 YVLSLINKSLD-NWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 778-1034 2.04e-44

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: 162.65  E-value: 2.04e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  778 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVlhSDTIANIQLNKSNMAATaafnkd 857
Cdd:cd05168     31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETI--PDTVSIDSLKKRFPNFT------ 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  858 ALLNWLKSK---NPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERV 934
Cdd:cd05168    103 SLLDYFERTfgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETA 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  935 PFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG-LPELSCSKD--IQYLKDSLALGKT 1011
Cdd:cd05168    181 PFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNLT 257

                          250       260
                   ....*....|....*....|...
gi 1868156914 1012 EEEaLKQFRVKFNEALRESWKTK 1034
Cdd:cd05168    258 EEE-CAQFVDSLIDKSLNNWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 750-985 1.58e-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: 154.80  E-value: 1.58e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  750 VEQCTFMDSKMKPLWImyssEEAGSAG-SVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGL 828
Cdd:cd00142      5 VGILKVIHSKQRPKKI----TLIGADGkTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  829 IEVVLHSDTIANiqlnksnmaataafnkdaLLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRE 907
Cdd:cd00142     81 IEIVKDAQTIED------------------LLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEP 142

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1868156914  908 SGQLFHIDFGHFLGNFKTKFGInrERVPFILTYDFVHVIQQGKTNNsekfeRFRGYCERAYTILRRHGLLFLHLFALM 985
Cdd:cd00142    143 SGNIFHIDFGFIFSGRKLAEGV--ETVPFRLTPMLENAMGTAGVNG-----PFQISMVKIMEILREHADLIVPILEHS 213
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 314-483 1.76e-41

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: 149.43  E-value: 1.76e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  314 VSLWSLEQPFCIELM--EGSKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWRQRLEFDINICDLPRMARLC 391
Cdd:cd08380      1 KSLWDINFNLRIKIHgiTNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  392 FALYAVvekakkarstKKKSRKADCPIAWANLMLFDYKDQLKTGERRLYMWPSVPDEkgellNPAGTVRSNPNTESAAAL 471
Cdd:cd08380     81 LSIYAV----------SEPGSKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPCNNSNENSTRL 145

                          170
                   ....*....|..
gi 1868156914  472 VIFLPEVaPHPV 483
Cdd:cd08380    146 LIELPEF-SKPV 156
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
638-1019 1.90e-36

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 150.32  E-value: 1.90e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  638 LDRALANRKIGHFLFWHL-RSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMKqgeaLSKLKALNDFVKVSSQKTTKPQTK 716
Cdd:COG5032   1657 ISVALLIDKPLHEERENFpSGLSLSSFQSSFLKELIKKSPRKIRKKFKIDIS----LLNLSRKLYISVLRSIRKRLKRLL 1732

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  717 EMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCVEQCTFMDSKMKPLWIMYSseeaGSAGSV-GIIFKNGDDLR 789
Cdd:COG5032   1733 ELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEPEVSVVKSHLQRPRRLTIR----GSDGKLySFIVKGGDDLR 1808

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  790 QDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANI------QLNKS-NMAATAAFNKDA 858
Cdd:COG5032   1809 QDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDN 1888

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  859 LLNWLKSKNPGEALD---------------------RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDF 916
Cdd:COG5032   1889 LKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFARSLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDF 1968

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  917 GHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPE---L 993
Cdd:COG5032   1969 GFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEwrrL 2042

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1868156914  994 SCSKDIQY-----LKDSLALGKTEEEALKQF 1019
Cdd:COG5032   2043 PCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 315-483 4.06e-36

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: 134.15  E-value: 4.06e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  315 SLWSLEQPFCIELMEGSKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVNvCSEPVWRQRLEFDINICDLPRMARLCFAL 394
Cdd:cd08398      2 SLWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLCDNVNTQRVP-CSNPRWNEWLDYDIYIPDLPRSARLCLSI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  395 YAVvekakkarSTKKKSRKADCPIAWANLMLFDYKDQLKTGERRLYMWPsVPDEKGELLNPAGTVRSNPNTESAAALVIF 474
Cdd:cd08398     81 CSV--------KGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWP-VPHGLEDLLNPIGVTGSNPNKDTPCLELEF 151


                   ....*....
gi 1868156914  475 lpEVAPHPV 483
Cdd:cd08398    152 --DRFSCVV 158
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.07e-35

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 129.56  E-value: 1.07e-35
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1868156914   34 FPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 1.22e-33

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: 125.10  E-value: 1.22e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  182 ILRVTNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVEQpeDYALQVNGRHEYLYGNYPLCQFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 1868156914  262 ICSCLHSGLTPHLTMVHASS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 312-407 3.71e-30

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 114.75  E-value: 3.71e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   312 SSVSLWSLEQPFCIELMEGSKVNADERM-KLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWRQRLEFDINICDLPRMARL 390
Cdd:smart00142    4 ESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARL 83

                            90
                    ....*....|....*..
gi 1868156914   391 CFALYAVVEKAKKARST 407
Cdd:smart00142   84 CITIYAVKNPSKGSEFG 100
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 505-660 7.42e-28

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: 110.50  E-value: 7.42e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  505 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNkheDVAQLSQMLYLLCSWPELPVLSAL 584
Cdd:cd00870      7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNN-KKALTKFLKSVNWS---DEQEVKQALELMPKWAKIDIEDAL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  585 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESY-------LDCELTKFLLDRALANRKIGHFLFWHLRS 657
Cdd:cd00870     83 ELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWYLKV 162


                   ...
gi 1868156914  658 EMH 660
Cdd:cd00870    163 ELE 165
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 506-660 6.74e-26

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: 105.23  E-value: 6.74e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  506 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLL-LVTKWnkheDVAQLSQMLYLLCSWPELPVLSAL 584
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNE-PNALPLVLaSAPSW----DWANLMDVYQLLHQWAPLRPLIAL 75

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1868156914  585 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMH 660
Cdd:cd00869     76 ELLLPKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALD 151
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 781-975 1.76e-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: 96.96  E-value: 1.76e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  781 IFKNGDDLRQDMLTLQMIQLMDVLWKQEG----LDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIqlnksnmaataaFNK 856
Cdd:cd05164     33 LVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLIEWVDNTTTLKPV------------LKK 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  857 DAllnWLKSKNPGEALDrAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTkFGINrERVP 935
Cdd:cd05164    101 WF---NETFPDPTQWYE-ARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFNKGKT-LPVP-EIVP 174

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1868156914  936 FILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRRHG 975
Cdd:cd05164    175 FRLTRNIINGMGPTGVEGL-----FRKSCEQVLRVFRKHK 209
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 339-448 2.43e-22

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


Pssm-ID: 395640  Cd Length: 136  Bit Score: 93.97  E-value: 2.43e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  339 MKLVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWRQRLEFDINICDLPRMARLCFALYAVvekakkarstkKKSRKADCP 417
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVP 71

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1868156914  418 IAWANLMLFDYKDQLKTGERRLYMWPSVPDE 448
Cdd:pfam00792   72 IGWVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 4.31e-21

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 88.31  E-value: 4.31e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1868156914    31 YLNFPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 756-975 2.00e-20

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


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 92.55  E-value: 2.00e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  756 MDSKMKP--LWIMysseeagsaGSVGIIF----KNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDR 825
Cdd:cd05169     11 ITSKQRPrkLTIV---------GSDGKEYkfllKGHEDLRLDERVMQLFGLVNTLLKNDsetsRRNLSIQRYSVIPLSPN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  826 TGLIEVVLHSDTIA----------NIQLN--KSNMAATA-------------AFN-----------KDALlnWLKSKNPG 869
Cdd:cd05169     82 SGLIGWVPGCDTLHslirdyrekrKIPLNieHRLMLQMApdydnltliqkveVFEyalentpgddlRRVL--WLKSPSSE 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  870 EALDRAIeEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFG-------HflgnfKTKFginRERVPFILTYD 941
Cdd:cd05169    160 AWLERRT-NFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRM 230

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1868156914  942 FVHVIQQGKTNNSekferFRGYCERAYTILRRHG 975
Cdd:cd05169    231 LVNAMEVSGVEGT-----FRSTCEDVMRVLRENK 259
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 751-947 5.90e-20

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


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 89.94  E-value: 5.90e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  751 EQCTFMDSKMKPLWI-MYSSEEAGSAgsvgIIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDR 825
Cdd:cd05172      6 PRVLVLSSKRRPKRItIRGSDEKEYK----FLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  826 TGLIEVVLHSDTIANIqlnksnmaataaFNKDALLNWLK--SKNPgEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNI 903
Cdd:cd05172     82 LGLIEWVDNTTPLKEI------------LENDLLRRALLslASSP-EAFLALRSNFARSLAAMSICGYILGIGDRHLSNF 148

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1868156914  904 MI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQ 947
Cdd:cd05172    149 LVdLSTGRLIGIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQ 192
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 776-974 3.48e-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: 3.48e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  776 GSVGI----IFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNKSN 847
Cdd:cd05171     24 GSDGKkykqLVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASS 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  848 ---------------------MAATAAFNKDALLN-----------------WLKSKNPGEALDRaIEEFTLSCAGYCVA 889
Cdd:cd05171    104 ksgaharyrpkdwtastcrkkMREKAKASAEERLKvfdeicknfkpvfrhffLEKFPDPSDWFER-RLAYTRSVATSSIV 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  890 TYVLGIGDRHSDNIMI-RESGQLFHIDFG-HFlgnfktKFGIN---RERVPFILTYDFVHVIQQGKTNNSekferFRGYC 964
Cdd:cd05171    183 GYILGLGDRHLNNILIdQKTGELVHIDLGiAF------EQGKLlpiPETVPFRLTRDIVDGMGITGVEGV-----FRRCC 251

                          250
                   ....*....|
gi 1868156914  965 ERAYTILRRH 974
Cdd:cd05171    252 EETLRVLREN 261
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 183-277 5.51e-18

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: 80.45  E-value: 5.51e-18
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914   183 LRVTNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPlVEQPEDYALQVNGRHEYLYGNYPLCQFQYI 262
Cdd:smart00144   11 LKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQV-DPTSEDYILKVCGRDEYLLGDHPLGSFEYI 89

                            90
                    ....*....|....*
gi 1868156914   263 CSCLHSGLTPHLTMV 277
Cdd:smart00144   90 RNCLKNGTEPHLVLM 104
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 345-479 2.78e-17

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: 80.48  E-value: 2.78e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  345 AGLFHGNEMLCKTVSSSEVNVCSE----PVWRQRLEFDINICDLPRMARLCFALYAVVEKAKKARSTKKKSRKadcPIAW 420
Cdd:cd04012     35 CSLYHGGRLLCSPVTTKPVKITKSffprVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGGSNKQRMGPE---ELGW 111

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  421 ANLMLFDYKDQLKTGERRLYMWPSVPDekgellNPAG-TVRSNPNTESAAALVIFLPEVA 479
Cdd:cd04012    112 VSLPLFDFRGVLRQGSLLLGLWPPSKD------NPLGpAPPPLFEQPDRVILQIDFPSSA 165
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 313-483 1.98e-16

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


Pssm-ID: 176044  Cd Length: 178  Bit Score: 78.41  E-value: 1.98e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  313 SVSLWSLEQPFCIELMeGSKVNADER---MKLVVQAGLFHGNEMLCKTVSSSEvNVCSEPVWRQRLEFDINICDLPRMAR 389
Cdd:cd08399      2 TVSLWDCDRKFRVKIL-GIDIPVLPRntdLTVFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGAL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  390 LCFALYAVvekaKKARSTKKKSRKADCP--------IAWANLMLFDYKDQLKTGERRLYMW--PSVPDEKGELLNPAGTV 459
Cdd:cd08399     80 LNLQIYCG----KAPALSSKKSAESPSSeskgkhqlLYYVNLLLIDHRFLLRTGEYVLHMWqiSGKGEDQGSVNADKLTS 155

                          170       180
                   ....*....|....*....|....
gi 1868156914  460 RSNPNTESAAALVIFLPEVApHPV 483
Cdd:cd08399    156 ATNPDKENSMSISILLDNYC-HPV 178
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 756-974 7.63e-16

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


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 77.93  E-value: 7.63e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  756 MDSKMKPLWIMYsseeAGSAG-SVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQ----EGLDLRMTPYGCLPTGDRTGLIE 830
Cdd:cd00892     11 MPSLQKPKKITL----VGSDGkKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLNEECGIIE 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  831 VVLHSDTIANIqLNKsnmaataaFNKDALLNWLKSK--NPGEALdRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RE 907
Cdd:cd00892     87 WVPNTVTLRSI-LST--------LYPPVLHEWFLKNfpDPTAWY-EARNNYTRSTAVMSMVGYILGLGDRHGENILFdST 156

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1868156914  908 SGQLFHIDFGHFLGNFKTkFGInRERVPFILTYDFVHVIqqGKTnnseKFE-RFRGYCERAYTILRRH 974
Cdd:cd00892    157 TGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAM--GVT----GVEgTFRRTCEVTLRVLREN 216
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 862-982 1.54e-08

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: 57.27  E-value: 1.54e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  862 WLKSKNPgEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIR-ESGQLFHIDF------GHFLgnfktkfginR--E 932
Cdd:cd05170    178 WCSSPSS-AEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpE 246

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1868156914  933 RVPFILTYDFVHVIqqGKTNnsekFE-RFRGYCERAYTILRRHGLLFLHLF 982
Cdd:cd05170    247 KVPFRLTQNIEHAL--GPTG----VEgTFRLSCEQVLKILRKGRETLLTLL 291
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 341-466 1.04e-07

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


Pssm-ID: 176042  Cd Length: 159  Bit Score: 52.64  E-value: 1.04e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  341 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWRQRLEFDINICDLPRMARLCFALYAVVekakkarstkkKSRKAdCPIAW 420
Cdd:cd08397     32 LFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDVS-----------GTGKA-VPFGG 99

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1868156914  421 ANLMLFDYKDQLKTGERRLYMWPSVPDEkGELLNPAGTVRSNPNTE 466
Cdd:cd08397    100 TTLSLFNKDGTLRRGRQKLRVWPDVEAD-GSIPTSTGKSPDSERDE 144
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 773-917 1.21e-07

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: 51.67  E-value: 1.21e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  773 GSAGSVGIIFKNGDDlRQDMLTLQMIQLMDVLWKQEGLDLrmTPYGCLPTGDRTG----LIEVVlhsdtianiqlnksnm 848
Cdd:cd13968     14 GECTTIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELV---------------- 74

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1868156914  849 aataafnKDALLNWLKSKnpGEALDRAIEEFTLSCAGYCVATYV--LGIGDRHSDNIMIRESGQLFHIDFG 917
Cdd:cd13968     75 -------KGGTLIAYTQE--EELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 542-659 1.27e-07

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: 52.74  E-value: 1.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1868156914  542 HFPEALArlLLVTKWNKHEDVAQLSQMLYllcsWPELPVLSALELLDFSFP-DCYVGSFAIKSLRKLTDDELFQYLLQLV 620
Cdd:cd00871     38 KIPEALP--FLVTGKSVDENSPDLKYLLY----WAPVSPVQALSLFTPQYPgHPLVLQYAVRVLESYPVETVFFYIPQIV 111

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1868156914  621 QVLKYESylDCELTKFLLDRALANRKIGHFLFWHLRSEM 659
Cdd:cd00871    112 QALRYDK--MGYVEEYILETAKRSQLFAHQIIWNMQTNC 148
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 878-939 6.24e-04

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


Pssm-ID: 270707  Cd Length: 252  Bit Score: 42.89  E-value: 6.24e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1868156914  878 EFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFgHFLGNFKTKFGINRERVPFILT 939
Cdd:cd05163    140 QFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDF-LPSINSQGPLLDNNEPVPFRLT 201
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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