NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|1726111164|ref|XP_030312224|]
View 

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [Calypte anna]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 702-1063 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: 776.83  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  702 MKVLAKQVEALNKMKTLNSLIKLNAMKQSKAKGKDAMHTCLKQNAYREALSDLQSPLNPSVILSELHVEKCRYMDSKMKP 781
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  782 LWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQL 861
Cdd:cd05173     81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  862 NSSNVAAAAAFNKDALLNWLKEYNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 941
Cdd:cd05173    161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  942 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQYLK 1021
Cdd:cd05173    241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1726111164 1022 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1063
Cdd:cd05173    321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 319-496 4.84e-96

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: 301.54  E-value: 4.84e-96
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  319 TSVWDISNPFKIVLLKGNKLNT-EENAKVHVRAGLFHGTELLCKTIVSSEISGRSDHVWNEVLEFEINVCDLPRMARLCF 397
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  398 AVYAVMDKMKTKKSTKamnpskYQTIRKAGKVHYPVAWVNTMVFDYKGQLKNGELVLHSWSSFPDELEEMLNPMGTVQTN 477
Cdd:cd08693     81 AIYEVSKKAKGKRSRK------NQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                          170
                   ....*....|....*....
gi 1726111164  478 PYTENATALHIRFQEYSKQ 496
Cdd:cd08693    155 PNTESATALHISFPEYKPE 173
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 533-698 2.29e-84

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: 270.34  E-value: 2.29e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  533 VLKEIMERDPLSQLCENEMDLIWTLRYDCReNFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPD 612
Cdd:cd00872      6 QLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDCNFPD 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  613 QYVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVHIPAVSVQFGLILE 692
Cdd:cd00872     85 EHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRFGLLLE 164


                   ....*.
gi 1726111164  693 AYCRGS 698
Cdd:cd00872    165 AYLRGC 170
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 175-282 2.95e-36

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: 132.45  E-value: 2.95e-36
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   175 EPVIPESFQDKLYSGNLVVAVHFDNCQDVFSFQVSPNMNPIKLNELAIRKRLTIHGKEDEEVDpaDYVLQVSGRLEYVFG 254
Cdd:smart00144    2 SPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE--DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*...
gi 1726111164   255 DHPLIQFQYIRNCVMNRTLPQLTLVECC 282
Cdd:smart00144   80 DHPLGSFEYIRNCLKNGTEPHLVLMTLS 107
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
38-111 1.12e-34

PI3-kinase family, p85-binding domain;


:

Pssm-ID: 460483  Cd Length: 74  Bit Score: 126.86  E-value: 1.12e-34
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1726111164   38 LDVPRDATISHIKQLLWKQAHAYPLFHLLMEIDSYMFSCVNQTAVHEELEDETRRLCDVRPFLPVLKLVTRNCD 111
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
 
Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 702-1063 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: 776.83  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  702 MKVLAKQVEALNKMKTLNSLIKLNAMKQSKAKGKDAMHTCLKQNAYREALSDLQSPLNPSVILSELHVEKCRYMDSKMKP 781
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  782 LWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQL 861
Cdd:cd05173     81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  862 NSSNVAAAAAFNKDALLNWLKEYNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 941
Cdd:cd05173    161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  942 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQYLK 1021
Cdd:cd05173    241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1726111164 1022 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1063
Cdd:cd05173    321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 319-496 4.84e-96

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: 301.54  E-value: 4.84e-96
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  319 TSVWDISNPFKIVLLKGNKLNT-EENAKVHVRAGLFHGTELLCKTIVSSEISGRSDHVWNEVLEFEINVCDLPRMARLCF 397
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  398 AVYAVMDKMKTKKSTKamnpskYQTIRKAGKVHYPVAWVNTMVFDYKGQLKNGELVLHSWSSFPDELEEMLNPMGTVQTN 477
Cdd:cd08693     81 AIYEVSKKAKGKRSRK------NQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                          170
                   ....*....|....*....
gi 1726111164  478 PYTENATALHIRFQEYSKQ 496
Cdd:cd08693    155 PNTESATALHISFPEYKPE 173
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 533-698 2.29e-84

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: 270.34  E-value: 2.29e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  533 VLKEIMERDPLSQLCENEMDLIWTLRYDCReNFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPD 612
Cdd:cd00872      6 QLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDCNFPD 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  613 QYVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVHIPAVSVQFGLILE 692
Cdd:cd00872     85 EHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRFGLLLE 164


                   ....*.
gi 1726111164  693 AYCRGS 698
Cdd:cd00872    165 AYLRGC 170
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 798-1015 2.57e-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: 2.57e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   798 IIFKNGDDLRQDMLTLQMLRLMDILWKE----AGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQLNS---------- 863
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   864 ------------SNVAAAAAFNKDALLNWLKEYNLGDDLD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQL 929
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   930 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLP 1009
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1726111164  1010 ELTSVK 1015
Cdd:smart00146  235 DWRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 796-1013 3.11e-73

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: 242.62  E-value: 3.11e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  796 VGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDL-RILPYGCLATGDHSGLIEAVSSSETIADIQLN--SSNVAAAAAF 872
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  873 N-----------------------KDALLNWLKEYNLG-DDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMV-RKNG 927
Cdd:pfam00454   82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  928 QLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAG 1007
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1726111164 1008 LPELTS 1013
Cdd:pfam00454  236 LPDWSI 241
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 534-707 5.97e-72

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: 236.77  E-value: 5.97e-72
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   534 LKEIMERDPLSQLCENEMDLIWTLRYDCRENFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPDQ 613
Cdd:smart00145   11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   614 YVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVHIPAVSVQFGLILEA 693
Cdd:smart00145   91 FVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                           170
                    ....*....|....
gi 1726111164   694 YCRGSVAHMKVLAK 707
Cdd:smart00145  171 YLRGCGTHLKELLK 184
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 533-707 6.36e-71

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


Pssm-ID: 395488  Cd Length: 185  Bit Score: 233.76  E-value: 6.36e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  533 VLKEIMERDPLSQLCENEMDLIWTLRYdCRENFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPD 612
Cdd:pfam00613   12 ELEAILAYDPLSKLTAEEKDLIWKFRY-YLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELLDPKFPD 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  613 QYVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVHIPAVSVQFGLILE 692
Cdd:pfam00613   91 PEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRFGSLLE 170

                          170
                   ....*....|....*
gi 1726111164  693 AYCRGSVAHMKVLAK 707
Cdd:pfam00613  171 LYLRSCGTSLLGLNK 185
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
706-1050 9.80e-37

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 151.47  E-value: 9.80e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  706 AKQVEALNKMKTLNSLIKLNAMKQSKAKGKDAMHTCLKQnAYREALSDLQSPLNPSVILSELHVEKCRYMDS-KMKPLWI 784
Cdd:COG5032   1709 LLNLSRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKShLQRPRRL 1787

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  785 vyNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGL----DLRILPYGCLATGDHSGLIEAVSSSETIADI- 859
Cdd:COG5032   1788 --TIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIl 1865

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  860 -----QLN-SSNVAAAAAFNKDALLNWLKEY-------------------NLGDDLD--RAIEEFTLSCAGYCVATYVLG 912
Cdd:COG5032   1866 reyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARSLAVYSVIGYILG 1945

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  913 IGDRHSDNIMV-RKNGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQYCEEAYLILRK 991
Cdd:COG5032   1946 LGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM--GVSG-VE--GSFRELCETAFRALRK 2019

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  992 HGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRESWT 1050
Cdd:COG5032   2020 NADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQAT 2089
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 175-282 2.95e-36

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: 132.45  E-value: 2.95e-36
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   175 EPVIPESFQDKLYSGNLVVAVHFDNCQDVFSFQVSPNMNPIKLNELAIRKRLTIHGKEDEEVDpaDYVLQVSGRLEYVFG 254
Cdd:smart00144    2 SPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE--DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*...
gi 1726111164   255 DHPLIQFQYIRNCVMNRTLPQLTLVECC 282
Cdd:smart00144   80 DHPLGSFEYIRNCLKNGTEPHLVLMTLS 107
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
38-111 1.12e-34

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 126.86  E-value: 1.12e-34
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1726111164   38 LDVPRDATISHIKQLLWKQAHAYPLFHLLMEIDSYMFSCVNQTAVHEELEDETRRLCDVRPFLPVLKLVTRNCD 111
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 175-282 3.53e-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: 123.56  E-value: 3.53e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  175 EPVIPESFQdKLYSGNLVVAVHFDNCQDVFSFQVSPNMNPIKLNELAIRKRLTIHGKEDEEvdpADYVLQVSGRLEYVFG 254
Cdd:pfam00794    2 STVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVT---DDYVLKVCGRDEYLLG 77

                           90       100
                   ....*....|....*....|....*...
gi 1726111164  255 DHPLIQFQYIRNCVMNRTLPQLTLVECC 282
Cdd:pfam00794   78 DHPLGQFEYIRNCLKSGREPHLTLVEQS 105
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 35-112 1.31e-31

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 118.35  E-value: 1.31e-31
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1726111164    35 YINLDVPRDATISHIKQLLWKQAHAYPLFHLLMEIDSYMFSCVNQTAVHEELEDETRRLCDVRPFLPVLKLVTRNCDP 112
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 316-412 1.79e-26

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 104.35  E-value: 1.79e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   316 RTTTSVWDISNPF--KIVLLKGNKLNTEEN-AKVHVRAGLFHGTELLCKTIVSSEISGRSDHVWNEVLEFEINVCDLPRM 392
Cdd:smart00142    1 VKIESLWDCDRNLviTIALIHGIPLNWSRDySDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90       100
                    ....*....|....*....|
gi 1726111164   393 ARLCFAVYAVMDKMKTKKST 412
Cdd:smart00142   81 ARLCITIYAVKNPSKGSEFG 100
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 345-466 5.45e-17

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: 78.56  E-value: 5.45e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  345 KVHVRAGLFHGTELLCKTIVSSEISGRSD-HVWNEVLEFEINVCDLPRMARLCFAVYAVMDKMKTKKstkamnpskyqti 423
Cdd:pfam00792    4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFV------------- 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1726111164  424 rkagkvhyPVAWVNTMVFDYKGQLKNGELVLHSWSSFPDELEE 466
Cdd:pfam00792   71 --------PIGWVNTSLFDKKGILRQGKQKLRLWPSKSTPGRS 105
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 813-938 5.60e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 44.31  E-value: 5.60e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  813 LQMLRLMDILWKEAgLDLRILPYGClatgdHSGLIEAVSSSETiadiqlnsSNVAaaaafNKDallnwLKEYNLGDDLDR 892
Cdd:PTZ00303  1074 LQMLLSSEIGNAEM-LDYSVLPLSC-----DSGLIEKAEGREL--------SNLD-----NMD-----IASYVLYRGTRS 1129

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1726111164  893 AIEeFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHIL 938
Cdd:PTZ00303  1130 CIN-FLASAKLFLLLNYIFSIGDRHKGNVLIGTNGALLHIDFRFIF 1174
 
Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 702-1063 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: 776.83  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  702 MKVLAKQVEALNKMKTLNSLIKLNAMKQSKAKGKDAMHTCLKQNAYREALSDLQSPLNPSVILSELHVEKCRYMDSKMKP 781
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  782 LWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQL 861
Cdd:cd05173     81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  862 NSSNVAAAAAFNKDALLNWLKEYNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 941
Cdd:cd05173    161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  942 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQYLK 1021
Cdd:cd05173    241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1726111164 1022 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1063
Cdd:cd05173    321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 701-1063 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: 641.72  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  701 HMKVLAKQVEALNKMKTLNSLIKLNAMKQSKAKGKDAMHTCLKQNAYREALSDLQSPLNPSVILSELHVEKCRYMDSKMK 780
Cdd:cd05174      3 HMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKMK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  781 PLWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQ 860
Cdd:cd05174     83 PLWIMYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQ 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  861 LNSSNVAAAAAFNKDALLNWLKEYNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGN 940
Cdd:cd05174    163 LNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGN 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  941 FKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQYL 1020
Cdd:cd05174    243 FKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQYL 322

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|...
gi 1726111164 1021 KDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1063
Cdd:cd05174    323 KDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 365
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 702-1062 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: 637.75  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  702 MKVLAKQVEALNKMKTLNSLIKlnAMKQSKAKGKDAMHTCLKQNAYREALSDLQSPLNPSVILSELHVEKCRYMDSKMKP 781
Cdd:cd05165      1 LKSLSRQVEALNKLKKLSDILK--EKKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  782 LWIVYNN---KMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIAD 858
Cdd:cd05165     79 LWLVFENadpLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  859 IQLNSSNVAAAAaFNKDALLNWLKEYN-LGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHI 937
Cdd:cd05165    159 IQKKKGKVATLA-FNKDSLHKWLKEKNkTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHF 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  938 LGNFKSKFGIKRERVPFILTYDFIHVIQQGKTG-NTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKD 1016
Cdd:cd05165    238 LGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKD 317

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 1726111164 1017 IQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRK 1062
Cdd:cd05165    318 IEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 702-1046 1.95e-156

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: 466.66  E-value: 1.95e-156
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  702 MKVLAKQVEALNKMKTLNSLIKlnamKQSKAKGKDAMHTCLKQNAYREALsdlQSPLNPSVILSELHVEKCRYMDSKMKP 781
Cdd:cd00891      1 REELLKQVKVLDELKEIAKKIK----EEPSEERKEVLEKLLQKLELPKKF---TLPLDPRMEVKGLIVEKCKVMDSKKLP 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  782 LWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQl 861
Cdd:cd00891     74 LWLVFKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQ- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  862 nSSNVAAAAAFNKDALLNWLKEYNLGD-DLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGN 940
Cdd:cd00891    153 -KKYGGFGAAFKDTPISNWLKKHNPTEeEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGN 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  941 FKSKFGIKRERVPFILTYDFIHVIqqgKTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQYL 1020
Cdd:cd00891    232 FKKKFGIKRERAPFVFTPEMAYVM---GGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYL 308

                          330       340
                   ....*....|....*....|....*.
gi 1726111164 1021 KDSLALGKSEEEALKQFKQKFDEALR 1046
Cdd:cd00891    309 RDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 705-1060 7.73e-115

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: 358.91  E-value: 7.73e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  705 LAKQVEALNKMKTLNSLIKlnamkqsKAKGKdamhtcLKQNAYREALSDLQS---------PLNPSVILSELHVEKCRYM 775
Cdd:cd05166      4 FLKQHVLVQALTSIAEKVK-------SAKDS------ARENALRRELEQLASfllensfrlPLDPALEVTGVDVRSCSYF 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  776 DSKMKPLWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSET 855
Cdd:cd05166     71 NSNALPLKLVFRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAET 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  856 IADIQlnsSNVAAAAAFNKDALLNWLKEYNLG-DDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDF 934
Cdd:cd05166    151 LREIQ---TEHGLTGSFKDRPLADWLQKHNPSeLEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDF 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  935 GHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSv 1014
Cdd:cd05166    228 GKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGDK-PSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQ- 305

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 1726111164 1015 KDIQYLKDSLALGKSEEEALKQFKQKFDEALReSWTTKVNWMAHTV 1060
Cdd:cd05166    306 DDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 701-1062 1.52e-110

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: 348.20  E-value: 1.52e-110
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  701 HMKVLAKQVEALNKMKTLNSLIKLNAMKQSKAKGKDAMHTCLKQNAYREALSDLQSPLNPSVILSELHVEKCRYMDSKMK 780
Cdd:cd05175      4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  781 PLWIVYNNKMFGGDLV----GIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETI 856
Cdd:cd05175     84 PLWLNWENPDIMSELLfqnnEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  857 ADIQLNSSnVAAAAAFNKDALLNWLKEYNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGH 936
Cdd:cd05175    164 MQIQCKGG-LKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  937 ILGNFKSKFGIKRERVPFILTYDFIHVIQQG--KTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSV 1014
Cdd:cd05175    243 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 322

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1726111164 1015 KDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRK 1062
Cdd:cd05175    323 DDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 752-1060 2.06e-108

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: 342.23  E-value: 2.06e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  752 SDLQSPLNPSVILSELHVEKCRYMDSKMKPLWIVY---NNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGL 828
Cdd:cd00894     53 ESFRVPYDPGLRAGALVIEKCKVMASKKKPLWLEFkcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESL 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  829 DLRILPYGCLATGDHSGLIEAVSSSETIADIQlnSSNVAAAAAFNKDALLNWLKEY-NLGDDLDRAIEEFTLSCAGYCVA 907
Cdd:cd00894    133 DLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKcPIEEKFQAAVERFVYSCAGYCVA 210

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  908 TYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEEAYL 987
Cdd:cd00894    211 TFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYL 290

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1726111164  988 ILRKHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTV 1060
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 ...
 319-496 4.84e-96

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: 301.54  E-value: 4.84e-96
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  319 TSVWDISNPFKIVLLKGNKLNT-EENAKVHVRAGLFHGTELLCKTIVSSEISGRSDHVWNEVLEFEINVCDLPRMARLCF 397
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  398 AVYAVMDKMKTKKSTKamnpskYQTIRKAGKVHYPVAWVNTMVFDYKGQLKNGELVLHSWSSFPDELEEMLNPMGTVQTN 477
Cdd:cd08693     81 AIYEVSKKAKGKRSRK------NQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                          170
                   ....*....|....*....
gi 1726111164  478 PYTENATALHIRFQEYSKQ 496
Cdd:cd08693    155 PNTESATALHISFPEYKPE 173
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 710-1060 1.37e-84

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


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 278.02  E-value: 1.37e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  710 EALNKMKTLNSLIKLNAMKQSKAKGKdamhtcLKQNAYREALSDLQS---------PLNPSVILSELHVEKCRYMDSKMK 780
Cdd:cd05176      2 EELEKQTRLVQLLGRVAEKVRQASGS------ARQVALQDGMERVQSffqknkcrlPLSPSLVAKELNIKACSFFSSNAV 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  781 PLWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQ 860
Cdd:cd05176     76 PLKVALVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQ 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  861 LNSSnvaAAAAFNKDALLNWLKEYNLG-DDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILG 939
Cdd:cd05176    156 VEYG---VTGSFKDKPLAEWLRKYNPSeEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLG 232

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  940 NFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQY 1019
Cdd:cd05176    233 HAQMFGSFKRDRAPFVLTSDMAYVINGGEK-PTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKY 311

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|.
gi 1726111164 1020 LKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 1060
Cdd:cd05176    312 VFDALQPQTTDAEATIFFTRLIESSL-GSVATKFNFFIHNL 351
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 533-698 2.29e-84

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: 270.34  E-value: 2.29e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  533 VLKEIMERDPLSQLCENEMDLIWTLRYDCReNFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPD 612
Cdd:cd00872      6 QLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDCNFPD 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  613 QYVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVHIPAVSVQFGLILE 692
Cdd:cd00872     85 EHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRFGLLLE 164


                   ....*.
gi 1726111164  693 AYCRGS 698
Cdd:cd00872    165 AYLRGC 170
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 703-1045 1.30e-80

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: 266.71  E-value: 1.30e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  703 KVLAKQVEALNKMKTLNSLIKlnAMKQSKAKGKDAMHTCLKQNAYREALSD--LQSPLNPSVILSELHVEKCRYMDSKMK 780
Cdd:cd00896      2 EALKRQQEFVDRLRSLMKEVK--NEKGSRDKKIERLRELLSDSELGLLLFFepLPLPLDPSVKVTGIIPEKSTVFKSALM 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  781 PLWIVYnnKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIq 860
Cdd:cd00896     80 PLKLTF--KTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  861 LNssnvaaaaafNKDALLNWLKEYNLGDD-----LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFG 935
Cdd:cd00896    157 LK----------KYGSILNFLRKHNPDESgpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFG 226

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  936 HILGN----FKSKFGIKRERVPFIltydfihviqqGKTgNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPEL 1011
Cdd:cd00896    227 YILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDI 294

                          330       340       350
                   ....*....|....*....|....*....|....*.
gi 1726111164 1012 TSVKD--IQYLKDSLALGKSEEEALKQFKQKFDEAL 1045
Cdd:cd00896    295 ALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 798-1015 2.57e-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: 2.57e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   798 IIFKNGDDLRQDMLTLQMLRLMDILWKE----AGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQLNS---------- 863
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   864 ------------SNVAAAAAFNKDALLNWLKEYNLGDDLD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQL 929
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   930 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLP 1009
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1726111164  1010 ELTSVK 1015
Cdd:smart00146  235 DWRSGK 240
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 757-1060 2.75e-79

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


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 263.29  E-value: 2.75e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  757 PLNPSVILSELHVEKCRYMDSKMKPLWIVYNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYG 836
Cdd:cd05177     53 PLNPALRVKGIDADACSYFTSNAAPLKISFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYR 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  837 CLATGDHSGLIEAVSSSETIADIQLNSSnvaAAAAFNKDALLNWLKEYN-LGDDLDRAIEEFTLSCAGYCVATYVLGIGD 915
Cdd:cd05177    133 CLSTGKTQGLVQMVPDAVTLAKIHRESG---LIGPLKENTIEKWFHMHNkLKEDYDKAVRNFFHSCAGWCVVTFILGVCD 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  916 RHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQYCEEAYLILRKHGNL 995
Cdd:cd05177    210 RHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSIKRDRAPFIFTSEMEYFITEGGK-KPQRFQRFVELCCRAYNIVRKHSQL 288

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1726111164  996 FITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 1060
Cdd:cd05177    289 LLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTL 352
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 743-1060 3.50e-75

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: 252.23  E-value: 3.50e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  743 KQNAYREALSDLQS----------PLNPSVILSELHVEKCRYMDSKMKPLWIVYNNKMFGGDLVGIIFKNGDDLRQDMLT 812
Cdd:cd00895     29 RQGILREGLEEVKQffsingscrlPLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDPLGENIRVIFKCGDDLRQDMLT 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  813 LQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQLNSSnvaAAAAFNKDALLNWLKEYNLG-DDLD 891
Cdd:cd00895    109 LQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG---VTGSFKDRPLADWLQKHNPTeDEYE 185

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  892 RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGN 971
Cdd:cd00895    186 KAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPS 265

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  972 TeKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTT 1051
Cdd:cd00895    266 S-RFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYFTRLIESSL-GSVAT 343


                   ....*....
gi 1726111164 1052 KVNWMAHTV 1060
Cdd:cd00895    344 KLNFFIHNL 352
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 796-1013 3.11e-73

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: 242.62  E-value: 3.11e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  796 VGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDL-RILPYGCLATGDHSGLIEAVSSSETIADIQLN--SSNVAAAAAF 872
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  873 N-----------------------KDALLNWLKEYNLG-DDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMV-RKNG 927
Cdd:pfam00454   82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  928 QLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAG 1007
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1726111164 1008 LPELTS 1013
Cdd:pfam00454  236 LPDWSI 241
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 534-707 5.97e-72

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: 236.77  E-value: 5.97e-72
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   534 LKEIMERDPLSQLCENEMDLIWTLRYDCRENFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPDQ 613
Cdd:smart00145   11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   614 YVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVHIPAVSVQFGLILEA 693
Cdd:smart00145   91 FVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                           170
                    ....*....|....
gi 1726111164   694 YCRGSVAHMKVLAK 707
Cdd:smart00145  171 YLRGCGTHLKELLK 184
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 533-707 6.36e-71

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


Pssm-ID: 395488  Cd Length: 185  Bit Score: 233.76  E-value: 6.36e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  533 VLKEIMERDPLSQLCENEMDLIWTLRYdCRENFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPD 612
Cdd:pfam00613   12 ELEAILAYDPLSKLTAEEKDLIWKFRY-YLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELLDPKFPD 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  613 QYVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVHIPAVSVQFGLILE 692
Cdd:pfam00613   91 PEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRFGSLLE 170

                          170
                   ....*....|....*
gi 1726111164  693 AYCRGSVAHMKVLAK 707
Cdd:pfam00613  171 LYLRSCGTSLLGLNK 185
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 534-679 7.34e-54

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: 184.73  E-value: 7.34e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  534 LKEIMERDPLSQLCENEMDLIWTLRYDCReNFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPDQ 613
Cdd:cd00864      7 LLAILLYPPFSTLTEEEKELLWKFRYYLL-NVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSPKYPDP 85

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1726111164  614 YVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVH 679
Cdd:cd00864     86 VVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 790-1052 9.74e-50

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: 177.84  E-value: 9.74e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  790 MFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQLNSsnvaaa 869
Cdd:cd00893     22 LKGWKLVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKL------ 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  870 AAFNKD-ALLNWLKEYNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIk 948
Cdd:cd00893     96 DSFNKFvSLSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF- 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  949 rERVPFILTYDFIHVIqqgKTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGK 1028
Cdd:cd00893    175 -EGAPFKLSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPEL 250

                          250       260
                   ....*....|....*....|....
gi 1726111164 1029 SEEEALKQFKQKFDEALReSWTTK 1052
Cdd:cd00893    251 TEGELEVYVLSLINKSLD-NWRTR 273
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 799-1052 8.81e-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: 175.86  E-value: 8.81e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  799 IFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVssSETIADIQLNSSNVaaaaafnkdall 878
Cdd:cd05167     53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVI--PNSKSRDQIGRETD------------ 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  879 NWLKEYNL---GDD----LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHIL-----GNfkskfg 946
Cdd:cd05167    119 NGLYEYFLskyGDEstpaFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFGFIFeispgGN------ 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  947 IKRERVPFILTYDFIHVIqqGKTGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTAGLPELTSvKDIQYLKDSLAL 1026
Cdd:cd05167    193 LGFESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRG-QTIKNLRERFAL 269

                          250       260
                   ....*....|....*....|....*.
gi 1726111164 1027 GKSEEEALKQFKQKFDEALrESWTTK 1052
Cdd:cd05167    270 EMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 794-1052 1.42e-48

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: 174.59  E-value: 1.42e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  794 DLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSGLIEAVSSSETIADIQLNSSNVaaaaafn 873
Cdd:cd05168     29 DLRSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNF------- 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  874 kDALLN-WLKEY--NLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIkrE 950
Cdd:cd05168    102 -TSLLDyFERTFgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--E 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  951 RVPFILTYDFIHVIqQGKtgNTEKFGRFRQYCEEAYLILRKHGNLFITLFALMLTA-------GLPELTsvkdIQYLKDS 1023
Cdd:cd05168    179 TAPFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGsklpcffGGGEFT----IEQLRER 251

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1726111164 1024 LALGKSEEealkQFKQKFDEALRES---WTTK 1052
Cdd:cd05168    252 FKLNLTEE----ECAQFVDSLIDKSlnnWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 766-1004 4.27e-44

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: 159.04  E-value: 4.27e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  766 ELHVEKCRYMDSKMKPLWIVYNNKmfGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGLDLRILPYGCLATGDHSG 845
Cdd:cd00142      2 ALDVGILKVIHSKQRPKKITLIGA--DGKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  846 LIEAVSSSETIADiqlnssnvaaaaafnkdaLLNWLKEYNLG-DDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVR 924
Cdd:cd00142     80 LIEIVKDAQTIED------------------LLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIE 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  925 KNGQLFHIDFGHILGNFKSKfgIKRERVPFILTYDFIHVIqqgktGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALML 1004
Cdd:cd00142    142 PSGNIFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAM-----GTAGVNGPFQISMVKIMEILREHADLIVPILEHSL 214
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 319-495 1.57e-43

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: 155.21  E-value: 1.57e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  319 TSVWDISNPFKIVLLKGNKLN--TEENAKVHVRAGLFHGTELLCKTIVSSEISGRSDHVWNEVLEFEINVCDLPRMARLC 396
Cdd:cd08380      1 KSLWDINFNLRIKIHGITNINllDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  397 FAVYAVMDKMKTKkstkamnpskyqtirkagkvHYPVAWVNTMVFDYKGQLKNGELVLHSWSSFPDEleemlNPMGTVQT 476
Cdd:cd08380     81 LSIYAVSEPGSKK--------------------EVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPC 135

                          170
                   ....*....|....*....
gi 1726111164  477 NPYTENATALHIRFQEYSK 495
Cdd:cd08380    136 NNSNENSTRLLIELPEFSK 154
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
706-1050 9.80e-37

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 151.47  E-value: 9.80e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  706 AKQVEALNKMKTLNSLIKLNAMKQSKAKGKDAMHTCLKQnAYREALSDLQSPLNPSVILSELHVEKCRYMDS-KMKPLWI 784
Cdd:COG5032   1709 LLNLSRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKShLQRPRRL 1787

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  785 vyNNKMFGGDLVGIIFKNGDDLRQDMLTLQMLRLMDILWKEAGL----DLRILPYGCLATGDHSGLIEAVSSSETIADI- 859
Cdd:COG5032   1788 --TIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIl 1865

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  860 -----QLN-SSNVAAAAAFNKDALLNWLKEY-------------------NLGDDLD--RAIEEFTLSCAGYCVATYVLG 912
Cdd:COG5032   1866 reyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARSLAVYSVIGYILG 1945

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  913 IGDRHSDNIMV-RKNGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQYCEEAYLILRK 991
Cdd:COG5032   1946 LGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM--GVSG-VE--GSFRELCETAFRALRK 2019

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  992 HGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRESWT 1050
Cdd:COG5032   2020 NADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQAT 2089
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 175-282 2.95e-36

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: 132.45  E-value: 2.95e-36
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   175 EPVIPESFQDKLYSGNLVVAVHFDNCQDVFSFQVSPNMNPIKLNELAIRKRLTIHGKEDEEVDpaDYVLQVSGRLEYVFG 254
Cdd:smart00144    2 SPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE--DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*...
gi 1726111164   255 DHPLIQFQYIRNCVMNRTLPQLTLVECC 282
Cdd:smart00144   80 DHPLGSFEYIRNCLKNGTEPHLVLMTLS 107
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
38-111 1.12e-34

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 126.86  E-value: 1.12e-34
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1726111164   38 LDVPRDATISHIKQLLWKQAHAYPLFHLLMEIDSYMFSCVNQTAVHEELEDETRRLCDVRPFLPVLKLVTRNCD 111
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 175-282 3.53e-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: 123.56  E-value: 3.53e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  175 EPVIPESFQdKLYSGNLVVAVHFDNCQDVFSFQVSPNMNPIKLNELAIRKRLTIHGKEDEEvdpADYVLQVSGRLEYVFG 254
Cdd:pfam00794    2 STVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVT---DDYVLKVCGRDEYLLG 77

                           90       100
                   ....*....|....*....|....*...
gi 1726111164  255 DHPLIQFQYIRNCVMNRTLPQLTLVECC 282
Cdd:pfam00794   78 DHPLGQFEYIRNCLKSGREPHLTLVEQS 105
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 35-112 1.31e-31

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 118.35  E-value: 1.31e-31
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1726111164    35 YINLDVPRDATISHIKQLLWKQAHAYPLFHLLMEIDSYMFSCVNQTAVHEELEDETRRLCDVRPFLPVLKLVTRNCDP 112
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 320-494 4.12e-30

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: 116.81  E-value: 4.12e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  320 SVWDISNPFKIVLLKGNKLNTEENAKVHVRAGLFHGTELLCkTIVSSEISGRSDHVWNEVLEFEINVCDLPRMARLCFAV 399
Cdd:cd08398      2 SLWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLC-DNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCLSI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  400 YAVMDKMKTKKStkamnpskyqtirkagkvHYPVAWVNTMVFDYKGQLKNGELVLHSWsSFPDELEEMLNPMGTVQTNPy 479
Cdd:cd08398     81 CSVKGRKGAKEE------------------HCPLAWGNINLFDYTDTLVSGKMALNLW-PVPHGLEDLLNPIGVTGSNP- 140

                          170
                   ....*....|....*
gi 1726111164  480 TENATALHIRFQEYS 494
Cdd:cd08398    141 NKDTPCLELEFDRFS 155
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 534-679 2.47e-27

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: 109.47  E-value: 2.47e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  534 LKEIMERDPLSQLCENEMDLIWTLRYDCRENFPQSLPKLLLSLKWnKLEDVAQLQALLQIWPKLLPREALELLDFNYPDQ 613
Cdd:cd00869      7 LLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSW-DWANLMDVYQLLHQWAPLRPLIALELLLPKFPDQ 85

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1726111164  614 YVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALANRRIGQMLFWHLRSEVH 679
Cdd:cd00869     86 EVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALD 151
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 316-412 1.79e-26

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 104.35  E-value: 1.79e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164   316 RTTTSVWDISNPF--KIVLLKGNKLNTEEN-AKVHVRAGLFHGTELLCKTIVSSEISGRSDHVWNEVLEFEINVCDLPRM 392
Cdd:smart00142    1 VKIESLWDCDRNLviTIALIHGIPLNWSRDySDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90       100
                    ....*....|....*....|
gi 1726111164   393 ARLCFAVYAVMDKMKTKKST 412
Cdd:smart00142   81 ARLCITIYAVKNPSKGSEFG 100
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 534-679 5.01e-26

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: 105.49  E-value: 5.01e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  534 LKEIMERDPLSQLCENEMDLIWTLRYDCReNFPQSLPKLLLSLKWNKLEDVAQLQALLQIWPKLLPREALELLDFNYPDQ 613
Cdd:cd00870     14 LNKILKYPPTTKLTDEEKDLIWKFRFYLT-NNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELLSPYFTNP 92

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1726111164  614 YVREYAVGCLKQMSDEELSQYLLQLVQVLKYE-------PFLDCALSRFLLERALANRRIGQMLFWHLRSEVH 679
Cdd:cd00870     93 VVRKYAVSRLKLASDEELLLYLLQLVQALKYEnldlsplPRLDSPLADFLIERALKNPKLANFLYWYLKVELE 165
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 799-1004 6.94e-24

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: 101.19  E-value: 6.94e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  799 IFKNGDDLRQDMLTLQMLRLMD-ILWKEAG---LDLRILPYGCLATGDHSGLIEAVSSSETIadiqlnssnvaaaaafnK 874
Cdd:cd05164     33 LVKGDDDLRKDERVMQLFQLLNtLLEKDKEtrkRNLTIRTYSVVPLSSQSGLIEWVDNTTTL-----------------K 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  875 DALLNWLKE-YNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMV-RKNGQLFHIDFGHILGnfKSKFGIKRERV 952
Cdd:cd05164     96 PVLKKWFNEtFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFN--KGKTLPVPEIV 173

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1726111164  953 PFILTYDFIHVIqqgktGNTEKFGRFRQYCEEAYLILRKHGNLFITLFALML 1004
Cdd:cd05164    174 PFRLTRNIINGM-----GPTGVEGLFRKSCEQVLRVFRKHKDKLITFLDTFL 220
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 775-965 1.46e-19

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


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 88.79  E-value: 1.46e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  775 MDSKMKPLWIvynnKMFGGD------LVgiifKNGDDLRQDMLTLQMLRLMDILWKE----AGLDLRILPYGCLATGDHS 844
Cdd:cd05172     11 LSSKRRPKRI----TIRGSDekeykfLV----KGGEDLRQDQRIQQLFDVMNNILASdpacRQRRLRIRTYQVIPMTSRL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  845 GLIEAVSSSETIADIqlnssnvaaaaaFNKDALLNWLkeYNLGDDLD-----RAieEFTLSCAGYCVATYVLGIGDRHSD 919
Cdd:cd05172     83 GLIEWVDNTTPLKEI------------LENDLLRRAL--LSLASSPEaflalRS--NFARSLAAMSICGYILGIGDRHLS 146

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1726111164  920 NIMV-RKNGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIQ 965
Cdd:cd05172    147 NFLVdLSTGRLIGIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQ 192
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 799-999 7.48e-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: 87.98  E-value: 7.48e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  799 IFKNGDDLRQDMLTLQMLRLMDILWKEAGL----DLRILPYGCLATGDHSGLIEAVSSSETIADIQLNSSNVAAAAafnk 874
Cdd:cd05171     33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSKSGAH---- 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  875 dallnwlKEYNLGDDLDRA----------------IEEFTLSCAGY---------------------------CVAT--- 908
Cdd:cd05171    109 -------ARYRPKDWTASTcrkkmrekakasaeerLKVFDEICKNFkpvfrhfflekfpdpsdwferrlaytrSVATssi 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  909 --YVLGIGDRHSDNIMV-RKNGQLFHIDFGHILGnfkskFGiKR----ERVPFILTYDFIHVIqqGKTGnTEkfGRFRQY 981
Cdd:cd05171    182 vgYILGLGDRHLNNILIdQKTGELVHIDLGIAFE-----QG-KLlpipETVPFRLTRDIVDGM--GITG-VE--GVFRRC 250

                          250
                   ....*....|....*...
gi 1726111164  982 CEEAYLILRKHGNLFITL 999
Cdd:cd05171    251 CEETLRVLRENKEALLTI 268
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 775-992 2.10e-18

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: 85.64  E-value: 2.10e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  775 MDSKMKPLWIVynnkMFG--GDLVGIIFKNGDDLRQDMltlqmlRLMD-------ILWKEA---GLDLRILPYGCLATGD 842
Cdd:cd00892     11 MPSLQKPKKIT----LVGsdGKKYPFLCKPKDDLRKDA------RMMEfntlinrLLSKDPesrRRNLHIRTYAVIPLNE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  843 HSGLIEAVSSSETIADIqlnssnvaaAAAFNKDALLNWLKEyNLGDDLD--RAIEEFTLSCAGYCVATYVLGIGDRHSDN 920
Cdd:cd00892     81 ECGIIEWVPNTVTLRSI---------LSTLYPPVLHEWFLK-NFPDPTAwyEARNNYTRSTAVMSMVGYILGLGDRHGEN 150

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1726111164  921 IMV-RKNGQLFHIDFGHILGNFKsKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQYCEEAYLILRKH 992
Cdd:cd00892    151 ILFdSTTGDVVHVDFDCLFDKGL-TLEVP-ERVPFRLTQNMVDAM--GVTG-VE--GTFRRTCEVTLRVLREN 216
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 347-494 1.05e-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: 81.64  E-value: 1.05e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  347 HVRAGLFHGTELLCKTIVSSEISGRSDH----VWNEVLEFEINVCDLPRMARLCFAVYAvmdkmktkksTKAMNPSKYQT 422
Cdd:cd04012     32 YLSCSLYHGGRLLCSPVTTKPVKITKSFfprvVWDEWIEFPIPVCQLPRESRLVLTLYG----------TTSSPDGGSNK 101

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1726111164  423 IRKAGKvhyPVAWVNTMVFDYKGQLKNGELVLHSWSSFPDeleEMLNPMGTvqTNPYTENATALHIRFQEYS 494
Cdd:cd04012    102 QRMGPE---ELGWVSLPLFDFRGVLRQGSLLLGLWPPSKD---NPLGPAPP--PLFEQPDRVILQIDFPSSA 165
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 345-466 5.45e-17

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: 78.56  E-value: 5.45e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  345 KVHVRAGLFHGTELLCKTIVSSEISGRSD-HVWNEVLEFEINVCDLPRMARLCFAVYAVMDKMKTKKstkamnpskyqti 423
Cdd:pfam00792    4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFV------------- 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1726111164  424 rkagkvhyPVAWVNTMVFDYKGQLKNGELVLHSWSSFPDELEE 466
Cdd:pfam00792   71 --------PIGWVNTSLFDKKGILRQGKQKLRLWPSKSTPGRS 105
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 318-493 5.95e-17

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: 79.96  E-value: 5.95e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  318 TTSVWDISNPFKIVLLKGNKLNTEENAK--VHVRAGLFHGTELLCKTIVSSEiSGRSDHVWNEVLEFEINVCDLPRMARL 395
Cdd:cd08399      2 TVSLWDCDRKFRVKILGIDIPVLPRNTDltVFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGALL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  396 CFAVYAVMDKMKTKKSTKAMNPSkyqtirKAGKVHYPVAWVNTMVFDYKGQLKNGELVLHSWS-SFPDELEEMLNP-MGT 473
Cdd:cd08399     81 NLQIYCGKAPALSSKKSAESPSS------ESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQiSGKGEDQGSVNAdKLT 154

                          170       180
                   ....*....|....*....|
gi 1726111164  474 VQTNPYTENATALHIRFQEY 493
Cdd:cd08399    155 SATNPDKENSMSISILLDNY 174
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 763-1006 3.70e-16

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: 79.83  E-value: 3.70e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  763 ILSELHVekcryMDSKMKP--LWIVYNNkmfggdlvGIIF----KNGDDLRQDMLTLQMLRLMDILWKE----AGLDLRI 832
Cdd:cd05169      4 FDPTLEV-----ITSKQRPrkLTIVGSD--------GKEYkfllKGHEDLRLDERVMQLFGLVNTLLKNdsetSRRNLSI 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  833 LPYGCLATGDHSGLIEAVSSSETIA----------DIQLN-SSNVAAAAAFNKDAL--------LNWLKEYNLGDDLDRA 893
Cdd:cd05169     71 QRYSVIPLSPNSGLIGWVPGCDTLHslirdyrekrKIPLNiEHRLMLQMAPDYDNLtliqkvevFEYALENTPGDDLRRV 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  894 I-------EE-------FTLSCAGYCVATYVLGIGDRHSDNIMV-RKNGQLFHIDFG-------HilgnfKSKFgikRER 951
Cdd:cd05169    151 LwlkspssEAwlerrtnFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEK 222

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1726111164  952 VPFILTYDFIHVIQQGKTGntekfGRFRQYCEEAYLILRKHGNlfiTLFAlMLTA 1006
Cdd:cd05169    223 VPFRLTRMLVNAMEVSGVE-----GTFRSTCEDVMRVLRENKD---SLMA-VLEA 268
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 892-1000 5.89e-13

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: 70.75  E-value: 5.89e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  892 RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVR-KNGQLFHIDF------GHILgnfkskfgikR--ERVPFILTYDFIH 962
Cdd:cd05170    189 RVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLTQNIEH 258

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1726111164  963 VIqqgktGNTEKFGRFRQYCEEAYLILRKHGNLFITLF 1000
Cdd:cd05170    259 AL-----GPTGVEGTFRLSCEQVLKILRKGRETLLTLL 291
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 789-935 1.55e-08

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 54.37  E-value: 1.55e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  789 KMFGGDLVGIIFKNGDDlRQDMLTLQMLRLMDILWKEAGLDLriLPYGCLATGDHSG----LIEAVSSSETIADIQLNSs 864
Cdd:cd13968     12 AEGECTTIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELVKGGTLIAYTQEEE- 87

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1726111164  865 nvaaaaafnkdallnwLKEynlgddldRAIEEFTLSCAGYCVATYV--LGIGDRHSDNIMVRKNGQLFHIDFG 935
Cdd:cd13968     88 ----------------LDE--------KDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 323-457 9.08e-07

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


Pssm-ID: 176042  Cd Length: 159  Bit Score: 49.94  E-value: 9.08e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  323 DISNPfkivLLKGNKLNTEENAKVHVRAGLFHGTELLCKTIVSSEISGRSDHVWNEVLEFEINVCDLPRMARLCFAVYAV 402
Cdd:cd08397     13 KLEDP----VLRFSGSNVSPNSDLFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDV 88

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1726111164  403 MDKMKTKkstkamnpskyqtirkagkvhyPVAWVNTMVFDYKGQLKNGELVLHSW 457
Cdd:cd08397     89 SGTGKAV----------------------PFGGTTLSLFNKDGTLRRGRQKLRVW 121
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 813-938 5.60e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 44.31  E-value: 5.60e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  813 LQMLRLMDILWKEAgLDLRILPYGClatgdHSGLIEAVSSSETiadiqlnsSNVAaaaafNKDallnwLKEYNLGDDLDR 892
Cdd:PTZ00303  1074 LQMLLSSEIGNAEM-LDYSVLPLSC-----DSGLIEKAEGREL--------SNLD-----NMD-----IASYVLYRGTRS 1129

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1726111164  893 AIEeFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHIL 938
Cdd:PTZ00303  1130 CIN-FLASAKLFLLLNYIFSIGDRHKGNVLIGTNGALLHIDFRFIF 1174
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 873-957 7.74e-03

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: 39.43  E-value: 7.74e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  873 NKDALLNW-LKEYNLGDDLDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMV-RKNGQLFHIDFGHILGNFKSKFGIKRE 950
Cdd:cd05163    116 PETILSNYfLRTMPSPSDLWLFRKQFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDFLPSINSQGPLLDNNEP 195


                   ....*..
gi 1726111164  951 rVPFILT 957
Cdd:cd05163    196 -VPFRLT 201
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 579-677 9.59e-03

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: 38.11  E-value: 9.59e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1726111164  579 NKLEDVAQLQALLQiWPKLLPREALELLDFNYPDQ-YVREYAVGCLKQMSDEELSQYLLQLVQVLKYEPflDCALSRFLL 657
Cdd:cd00871     51 SVDENSPDLKYLLY-WAPVSPVQALSLFTPQYPGHpLVLQYAVRVLESYPVETVFFYIPQIVQALRYDK--MGYVEEYIL 127

                           90       100
                   ....*....|....*....|
gi 1726111164  658 ERALANRRIGQMLFWHLRSE 677
Cdd:cd00871    128 ETAKRSQLFAHQIIWNMQTN 147
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH