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Conserved domains on  [gi|1597423504|gb|TEA30074|]
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hypothetical protein DBR06_SOUSAS27110012, partial [Sousa chinensis]

Protein Classification

Graphical summary

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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 ...
 623-984 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: 769.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 623 MKALSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQNAYREALSDLQSPLNPCVILSELYIEKCKYMDSKMKP 702
Cdd:cd05173     1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 703 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQL 782
Cdd:cd05173    81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 783 NSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 862
Cdd:cd05173   161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 863 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 942
Cdd:cd05173   241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 1597423504 943 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVWKD 984
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 ...
 268-445 3.11e-92

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


:

Pssm-ID: 176075  Cd Length: 173  Bit Score: 290.37  E-value: 3.11e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 268 SHVWENNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTIVSSEISGKNDHIWNEPLEFDINTCDLPRMARLCF 346
Cdd:cd08693     1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 347 AVYAVLDKVKTKKSTKainpskYQTIRKSGKVDYPVAWVNTMVFYFKGQLRSGDIILHSWSSFPDELEEMLNPMGTVQTN 426
Cdd:cd08693    81 AIYEVSKKAKGKRSRK------NQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                         170
                  ....*....|....*....
gi 1597423504 427 PYTENATALHIRFPENKKQ 445
Cdd:cd08693   155 PNTESATALHISFPEYKPE 173
PI3Ka super family cl00271
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 476-620 2.21e-70

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.


The actual alignment was detected with superfamily member cd00872:

Pssm-ID: 412275  Cd Length: 171  Bit Score: 231.05  E-value: 2.21e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 476 KKFLAVLKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 555
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 556 FNYPDQYVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIPAVSVQF 608
Cdd:cd00872    80 CNFPDEHVREFAVRCLEKLsddellqyllqlvqvlkyepyhdsdlvRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                         170
                  ....*....|..
gi 1597423504 609 GVILEAYCRGSI 620
Cdd:cd00872   160 GLLLEAYLRGCG 171
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 124-232 7.44e-44

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: 154.02  E-value: 7.44e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  124 HEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKINELAIQKRLTIHGKEDEVSPyDYVLQVSGRVEYVFG 203
Cdd:smart00144   1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                           90       100
                   ....*....|....*....|....*....
gi 1597423504  204 DHPLIQFQYIRNCVMNRTLPHFILVECCK 232
Cdd:smart00144  80 DHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_p85B super family cl02483
PI3-kinase family, p85-binding domain;
1-62 1.37e-27

PI3-kinase family, p85-binding domain;


The actual alignment was detected with superfamily member smart00143:

Pssm-ID: 470589  Cd Length: 78  Bit Score: 106.80  E-value: 1.37e-27
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1597423504    1 QMLWKQVHNYPMFNLLMEIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 62
Cdd:smart00143  17 HELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
 
Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 623-984 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: 769.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 623 MKALSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQNAYREALSDLQSPLNPCVILSELYIEKCKYMDSKMKP 702
Cdd:cd05173     1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 703 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQL 782
Cdd:cd05173    81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 783 NSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 862
Cdd:cd05173   161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 863 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 942
Cdd:cd05173   241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 1597423504 943 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVWKD 984
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 ...
 268-445 3.11e-92

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


Pssm-ID: 176075  Cd Length: 173  Bit Score: 290.37  E-value: 3.11e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 268 SHVWENNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTIVSSEISGKNDHIWNEPLEFDINTCDLPRMARLCF 346
Cdd:cd08693     1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 347 AVYAVLDKVKTKKSTKainpskYQTIRKSGKVDYPVAWVNTMVFYFKGQLRSGDIILHSWSSFPDELEEMLNPMGTVQTN 426
Cdd:cd08693    81 AIYEVSKKAKGKRSRK------NQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                         170
                  ....*....|....*....
gi 1597423504 427 PYTENATALHIRFPENKKQ 445
Cdd:cd08693   155 PNTESATALHISFPEYKPE 173
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 719-936 6.36e-81

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: 262.62  E-value: 6.36e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  719 VIFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQLNS---------- 784
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  785 ------------SNVAAAAAFNKDALLNWLKEYNSGDDLD--RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQL 850
Cdd:smart00146  81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  851 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLP 930
Cdd:smart00146 161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                   ....*.
gi 1597423504  931 ELTSVK 936
Cdd:smart00146 235 DWRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 716-934 8.84e-75

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: 245.70  E-value: 8.84e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 716 SVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDL-RMLPYGCLATGDHSGLIEVVSTSETIADIQLN--SSNVAAAAA 792
Cdd:pfam00454   1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 793 FN-----------------------KDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKK-T 847
Cdd:pfam00454  81 VKilhsalnypklklefesrislppKVGLLQWFVKKSpDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDKtT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 848 GQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTA 927
Cdd:pfam00454 161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                  ....*..
gi 1597423504 928 GLPELTS 934
Cdd:pfam00454 235 GLPDWSI 241
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 476-620 2.21e-70

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: 231.05  E-value: 2.21e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 476 KKFLAVLKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 555
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 556 FNYPDQYVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIPAVSVQF 608
Cdd:cd00872    80 CNFPDEHVREFAVRCLEKLsddellqyllqlvqvlkyepyhdsdlvRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                         170
                  ....*....|..
gi 1597423504 609 GVILEAYCRGSI 620
Cdd:cd00872   160 GLLLEAYLRGCG 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 470-628 5.68e-58

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: 197.17  E-value: 5.68e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 470 VSSRGGKKFLAVLKEILDRDPLSQLCENEMDLIWTLRqDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPRE 549
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFR-YYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 550 ALELLDFNYPDQYVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIP 602
Cdd:pfam00613  80 ALELLDPKFPDPEVRQYAVKCLESAsddellfyllqlvqalkyepfhdsylsRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                         170       180
                  ....*....|....*....|....*.
gi 1597423504 603 AVSVQFGVILEAYCRGSIGHMKALSK 628
Cdd:pfam00613 160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 482-628 1.20e-57

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


Pssm-ID: 214537  Cd Length: 184  Bit Score: 196.32  E-value: 1.20e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  482 LKEILDRDPLSQLCENEMDLIWTLRQDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 561
Cdd:smart00145  11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  562 YVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIPAVSVQFGVILEA 614
Cdd:smart00145  91 FVRAYAVKRLESAsdeelllyllqlvqalkyepyldsalaRFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                          170
                   ....*....|....
gi 1597423504  615 YCRGSIGHMKALSK 628
Cdd:smart00145 171 YLRGCGTHLKELLK 184
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 124-232 7.44e-44

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: 154.02  E-value: 7.44e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  124 HEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKINELAIQKRLTIHGKEDEVSPyDYVLQVSGRVEYVFG 203
Cdd:smart00144   1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                           90       100
                   ....*....|....*....|....*....
gi 1597423504  204 DHPLIQFQYIRNCVMNRTLPHFILVECCK 232
Cdd:smart00144  80 DHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 124-232 7.02e-38

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: 137.04  E-value: 7.02e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 124 HEPSIPENLEdKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKINELAIQKRLTIHGKEDEVSpyDYVLQVSGRVEYVFG 203
Cdd:pfam00794   1 ASTVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLG 77

                          90       100
                  ....*....|....*....|....*....
gi 1597423504 204 DHPLIQFQYIRNCVMNRTLPHFILVECCK 232
Cdd:pfam00794  78 DHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
624-971 6.29e-35

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 145.31  E-value: 6.29e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  624 KALSKQVEALNK-----LKTLNSLIKLNAMKLNRAKGKEAMHTCLKQnAYREALSDLQSPLNPCVILSELYIEKCKYMDS 698
Cdd:COG5032   1701 KKFKIDISLLNLsrklyISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKS 1779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  699 -KMKPlwlvynNKVFGEDSVG----VIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDHSGLIE 769
Cdd:COG5032   1780 hLQRP------RRLTIRGSDGklysFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIE 1853

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  770 VVSTSETIADI------QLN-SSNVAAAAAFNKDALLNWLKEY-------------------NSGDDLD--RAIEEFTLS 821
Cdd:COG5032   1854 WVPNSDTLHSIlreyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARS 1933

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  822 CAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFR 900
Cdd:COG5032   1934 LAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM-----GVSGVEGSFR 2007

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  901 QCCEDAYLILRRHGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRES 969
Cdd:COG5032   2008 ELCETAFRALRKNADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQ 2087


                   ..
gi 1597423504  970 WT 971
Cdd:COG5032   2088 AT 2089
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 265-361 6.24e-28

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 108.59  E-value: 6.24e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  265 RIISHVWENNNPFQ--IVLVKGNKLNTEETV-KVHVRAGLFHGTELLCKTIVSSEISGKNDHIWNEPLEFDINTCDLPRM 341
Cdd:smart00142   1 VKIESLWDCDRNLVitIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                           90       100
                   ....*....|....*....|
gi 1597423504  342 ARLCFAVYAVLDKVKTKKST 361
Cdd:smart00142  81 ARLCITIYAVKNPSKGSEFG 100
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 1-62 1.37e-27

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 106.80  E-value: 1.37e-27
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1597423504    1 QMLWKQVHNYPMFNLLMEIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 62
Cdd:smart00143  17 HELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
1-61 1.94e-24

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 97.59  E-value: 1.94e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1597423504   1 QMLWKQVHNYPMFNLLMEIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCD 61
Cdd:pfam02192  14 EELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 294-415 7.33e-16

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: 75.10  E-value: 7.33e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 294 KVHVRAGLFHGTELLCKTIVSSEISGKNDHI-WNEPLEFDINTCDLPRMARLCFAVYAVLDKVKTKKstkainpskyqti 372
Cdd:pfam00792   4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFV------------- 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1597423504 373 rksgkvdyPVAWVNTMVFYFKGQLRSGDIILHSWSSFPDELEE 415
Cdd:pfam00792  71 --------PIGWVNTSLFDKKGILRQGKQKLRLWPSKSTPGRS 105
 
Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 623-984 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: 769.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 623 MKALSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQNAYREALSDLQSPLNPCVILSELYIEKCKYMDSKMKP 702
Cdd:cd05173     1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 703 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQL 782
Cdd:cd05173    81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 783 NSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 862
Cdd:cd05173   161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 863 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 942
Cdd:cd05173   241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 1597423504 943 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVWKD 984
Cdd:cd05173   321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 623-981 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: 643.53  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 623 MKALSKQVEALNKLKTLNSLIKlnAMKLNRAKGKEAMHTCLKQNAYREALSDLQSPLNPCVILSELYIEKCKYMDSKMKP 702
Cdd:cd05165     1 LKSLSRQVEALNKLKKLSDILK--EKKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 703 LWLVYNN---KVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIAD 779
Cdd:cd05165    79 LWLVFENadpLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 780 IQLNSSNVAAAAaFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHI 858
Cdd:cd05165   159 IQKKKGKVATLA-FNKDSLHKWLKEKNkTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHF 237

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 859 LGNFKSKFGIKRERVPFILTYDFIHVIQQGKTG-NTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKD 937
Cdd:cd05165   238 LGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKD 317

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....
gi 1597423504 938 IQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTV 981
Cdd:cd05165   318 IEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNV 361
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 622-984 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: 638.63  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 622 HMKALSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQNAYREALSDLQSPLNPCVILSELYIEKCKYMDSKMK 701
Cdd:cd05174     3 HMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKMK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 702 PLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQ 781
Cdd:cd05174    83 PLWIMYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQ 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 782 LNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGN 861
Cdd:cd05174   163 LNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGN 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 862 FKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYL 941
Cdd:cd05174   243 FKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQYL 322

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 1597423504 942 KDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVWKD 984
Cdd:cd05174   323 KDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 365
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 623-967 4.74e-160

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: 473.60  E-value: 4.74e-160
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 623 MKALSKQVEALNKLKTLNSLIKlnamKLNRAKGKEAMHTCLKQNAYREALsdlQSPLNPCVILSELYIEKCKYMDSKMKP 702
Cdd:cd00891     1 REELLKQVKVLDELKEIAKKIK----EEPSEERKEVLEKLLQKLELPKKF---TLPLDPRMEVKGLIVEKCKVMDSKKLP 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 703 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQl 782
Cdd:cd00891    74 LWLVFKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQ- 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 783 nSSNVAAAAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGN 861
Cdd:cd00891   153 -KKYGGFGAAFKDTPISNWLKKHNpTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGN 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 862 FKSKFGIKRERVPFILTYDFIHVIqqgKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYL 941
Cdd:cd00891   232 FKKKFGIKRERAPFVFTPEMAYVM---GGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYL 308

                         330       340
                  ....*....|....*....|....*.
gi 1597423504 942 KDSLALGKSEEEALKQFKQKFDEALR 967
Cdd:cd00891   309 RDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 626-981 9.07e-117

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


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 361.99  E-value: 9.07e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 626 LSKQVEALNKLKTLnsliklnAMKLNRAKGKEamhtclKQNAYREALSDLQS---------PLNPCVILSELYIEKCKYM 696
Cdd:cd05166     4 FLKQHVLVQALTSI-------AEKVKSAKDSA------RENALRRELEQLASfllensfrlPLDPALEVTGVDVRSCSYF 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 697 DSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSET 776
Cdd:cd05166    71 NSNALPLKLVFRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAET 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 777 IADIQLNSSNVAAaaaFNKDALLNWLKEYNSG-DDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDF 855
Cdd:cd05166   151 LREIQTEHGLTGS---FKDRPLADWLQKHNPSeLEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDF 227

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 856 GHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRF-RQCCEdAYLILRRHGNLFITLFALMLTAGLPELTS 934
Cdd:cd05166   228 GKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGDK-PSSRFQLFvDLCCQ-AFNIIRKNSNLLLNLLSLMLSSGIPGVTQ 305

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 1597423504 935 vKDIQYLKDSLALGKSEEEALKQFKQKFDEALReSWTTKVNWMAHTV 981
Cdd:cd05166   306 -DDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 673-981 8.53e-111

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: 346.85  E-value: 8.53e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 673 SDLQSPLNPCVILSELYIEKCKYMDSKMKPLWLVY---NNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL 749
Cdd:cd00894    53 ESFRVPYDPGLRAGALVIEKCKVMASKKKPLWLEFkcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESL 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 750 DLRMLPYGCLATGDHSGLIEVVSTSETIADIQlnSSNVAAAAAFNKDALLNWLKEYNSGDD-LDRAIEEFTLSCAGYCVA 828
Cdd:cd00894   133 DLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPIEEkFQAAVERFVYSCAGYCVA 210

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 829 SYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYL 908
Cdd:cd00894   211 TFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYL 290

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1597423504 909 ILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTV 981
Cdd:cd00894   291 ALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 622-981 6.97e-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: 344.73  E-value: 6.97e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 622 HMKALSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQNAYREALSDLQSPLNPCVILSELYIEKCKYMDSKMK 701
Cdd:cd05175     4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 702 PLWLVYNN-KVFGE---DSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETI 777
Cdd:cd05175    84 PLWLNWENpDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 778 ADIQLNSSnVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGH 857
Cdd:cd05175   164 MQIQCKGG-LKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 858 ILGNFKSKFGIKRERVPFILTYDFIHVIQQG--KTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSV 935
Cdd:cd05175   243 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 322

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*.
gi 1597423504 936 KDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTV 981
Cdd:cd05175   323 DDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTI 368
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 268-445 3.11e-92

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


Pssm-ID: 176075  Cd Length: 173  Bit Score: 290.37  E-value: 3.11e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 268 SHVWENNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTIVSSEISGKNDHIWNEPLEFDINTCDLPRMARLCF 346
Cdd:cd08693     1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 347 AVYAVLDKVKTKKSTKainpskYQTIRKSGKVDYPVAWVNTMVFYFKGQLRSGDIILHSWSSFPDELEEMLNPMGTVQTN 426
Cdd:cd08693    81 AIYEVSKKAKGKRSRK------NQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                         170
                  ....*....|....*....
gi 1597423504 427 PYTENATALHIRFPENKKQ 445
Cdd:cd08693   155 PNTESATALHISFPEYKPE 173
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 631-981 3.72e-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: 275.70  E-value: 3.72e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 631 EALNKLKTLNSLIKLNAMKLNRAKGKeamhtcLKQNAYREALSDLQS---------PLNPCVILSELYIEKCKYMDSKMK 701
Cdd:cd05176     2 EELEKQTRLVQLLGRVAEKVRQASGS------ARQVALQDGMERVQSffqknkcrlPLSPSLVAKELNIKACSFFSSNAV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 702 PLWL-VYNNKVFGEDsVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADI 780
Cdd:cd05176    76 PLKVaLVNADPLGEE-INVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKI 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 781 QLNSSnvaAAAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHIL 859
Cdd:cd05176   155 QVEYG---VTGSFKDKPLAEWLRKYNpSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFL 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 860 GNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQ 939
Cdd:cd05176   232 GHAQMFGSFKRDRAPFVLTSDMAYVINGGEK-PTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLK 310

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 1597423504 940 YLKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 981
Cdd:cd05176   311 YVFDALQPQTTDAEATIFFTRLIESSL-GSVATKFNFFIHNL 351
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 719-936 6.36e-81

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: 262.62  E-value: 6.36e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  719 VIFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQLNS---------- 784
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  785 ------------SNVAAAAAFNKDALLNWLKEYNSGDDLD--RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQL 850
Cdd:smart00146  81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  851 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLP 930
Cdd:smart00146 161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                   ....*.
gi 1597423504  931 ELTSVK 936
Cdd:smart00146 235 DWRSGK 240
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 678-981 3.49e-78

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


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 259.44  E-value: 3.49e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 678 PLNPCVILSELYIEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYG 757
Cdd:cd05177    53 PLNPALRVKGIDADACSYFTSNAAPLKISFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYR 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 758 CLATGDHSGLIEVVSTSETIADIQLNSSnvaAAAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGD 836
Cdd:cd05177   133 CLSTGKTQGLVQMVPDAVTLAKIHRESG---LIGPLKENTIEKWFHMHNkLKEDYDKAVRNFFHSCAGWCVVTFILGVCD 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 837 RHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQCCEDAYLILRRHGNL 916
Cdd:cd05177   210 RHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSIKRDRAPFIFTSEMEYFITEGGK-KPQRFQRFVELCCRAYNIVRKHSQL 288

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1597423504 917 FITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 981
Cdd:cd05177   289 LLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTL 352
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 624-966 3.18e-77

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


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 256.30  E-value: 3.18e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 624 KALSKQVEALNKLKTLNSLIKlnAMKLNRAKGKEAMHTCLKQNAYREALSD--LQSPLNPCVILSELYIEKCKYMDSKMK 701
Cdd:cd00896     2 EALKRQQEFVDRLRSLMKEVK--NEKGSRDKKIERLRELLSDSELGLLLFFepLPLPLDPSVKVTGIIPEKSTVFKSALM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 702 PLWLVYNNKVFGEdsVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIq 781
Cdd:cd00896    80 PLKLTFKTLDGGE--YKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 782 LNssnvaaaaafNKDALLNWLKEYNsGDDLDR------AIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDF 855
Cdd:cd00896   157 LK----------KYGSILNFLRKHN-PDESGPygikpeVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDF 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 856 GHILGN----FKSKFGIKRERVPFIltydfihviqqGKTgNTEKFGRFRQ-CCEdAYLILRRHGNLFITLFALMLTAGLP 930
Cdd:cd00896   226 GYILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKyCCT-AYNILRKHANLILNLFSLMVDANIP 292

                         330       340       350
                  ....*....|....*....|....*....|....*...
gi 1597423504 931 ELTSVKD--IQYLKDSLALGKSEEEALKQFKQKFDEAL 966
Cdd:cd00896   293 DIALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 664-981 1.72e-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: 1.72e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 664 KQNAYREALSDLQS----------PLNPCVILSELYIEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLT 733
Cdd:cd00895    29 RQGILREGLEEVKQffsingscrlPLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDPLGENIRVIFKCGDDLRQDMLT 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 734 LQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQLNSSnvaAAAAFNKDALLNWLKEYNSG-DDLD 812
Cdd:cd00895   109 LQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG---VTGSFKDRPLADWLQKHNPTeDEYE 185

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 813 RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGN 892
Cdd:cd00895   186 KAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPS 265

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 893 TeKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTT 972
Cdd:cd00895   266 S-RFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYFTRLIESSL-GSVAT 343


                  ....*....
gi 1597423504 973 KVNWMAHTV 981
Cdd:cd00895   344 KLNFFIHNL 352
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 716-934 8.84e-75

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: 245.70  E-value: 8.84e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 716 SVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDL-RMLPYGCLATGDHSGLIEVVSTSETIADIQLN--SSNVAAAAA 792
Cdd:pfam00454   1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 793 FN-----------------------KDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKK-T 847
Cdd:pfam00454  81 VKilhsalnypklklefesrislppKVGLLQWFVKKSpDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDKtT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 848 GQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTA 927
Cdd:pfam00454 161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                  ....*..
gi 1597423504 928 GLPELTS 934
Cdd:pfam00454 235 GLPDWSI 241
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 476-620 2.21e-70

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: 231.05  E-value: 2.21e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 476 KKFLAVLKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 555
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 556 FNYPDQYVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIPAVSVQF 608
Cdd:cd00872    80 CNFPDEHVREFAVRCLEKLsddellqyllqlvqvlkyepyhdsdlvRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                         170
                  ....*....|..
gi 1597423504 609 GVILEAYCRGSI 620
Cdd:cd00872   160 GLLLEAYLRGCG 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 470-628 5.68e-58

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: 197.17  E-value: 5.68e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 470 VSSRGGKKFLAVLKEILDRDPLSQLCENEMDLIWTLRqDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPRE 549
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFR-YYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 550 ALELLDFNYPDQYVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIP 602
Cdd:pfam00613  80 ALELLDPKFPDPEVRQYAVKCLESAsddellfyllqlvqalkyepfhdsylsRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                         170       180
                  ....*....|....*....|....*.
gi 1597423504 603 AVSVQFGVILEAYCRGSIGHMKALSK 628
Cdd:pfam00613 160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 482-628 1.20e-57

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


Pssm-ID: 214537  Cd Length: 184  Bit Score: 196.32  E-value: 1.20e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  482 LKEILDRDPLSQLCENEMDLIWTLRQDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 561
Cdd:smart00145  11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  562 YVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIPAVSVQFGVILEA 614
Cdd:smart00145  91 FVRAYAVKRLESAsdeelllyllqlvqalkyepyldsalaRFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                          170
                   ....*....|....
gi 1597423504  615 YCRGSIGHMKALSK 628
Cdd:smart00145 171 YLRGCGTHLKELLK 184
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 718-973 5.16e-50

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


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 179.33  E-value: 5.16e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 718 GVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVstSETIADIQLNSSNVaaaaafnkda 797
Cdd:cd05167    51 AAIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVI--PNSKSRDQIGRETD---------- 118

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 798 llNWLKEYNS---GDD----LDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHIL-----GNfksk 865
Cdd:cd05167   119 --NGLYEYFLskyGDEstpaFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFGFIFeispgGN---- 192

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 866 fgIKRERVPFILTYDFIHVIqqGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSvKDIQYLKDSL 945
Cdd:cd05167   193 --LGFESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRG-QTIKNLRERF 267

                         250       260
                  ....*....|....*....|....*...
gi 1597423504 946 ALGKSEEEALKQFKQKFDEALrESWTTK 973
Cdd:cd05167   268 ALEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 717-973 3.38e-48

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


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 173.22  E-value: 3.38e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 717 VGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQLNSsnvaaaAAFNKD 796
Cdd:cd00893    28 VSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKL------DSFNKF 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 797 -ALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIkrERVPF 875
Cdd:cd00893   102 vSLSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPF 179

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 876 ILTYDFIHVIqqgKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEAL 955
Cdd:cd00893   180 KLSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELE 256

                         250
                  ....*....|....*...
gi 1597423504 956 KQFKQKFDEALReSWTTK 973
Cdd:cd00893   257 VYVLSLINKSLD-NWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 717-973 1.33e-46

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


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 168.81  E-value: 1.33e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 717 VGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIQLNSSNVaaaaafnkD 796
Cdd:cd05168    31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNF--------T 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 797 ALLN-WLKEY--NSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIkrERV 873
Cdd:cd05168   103 SLLDyFERTFgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETA 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 874 PFILTYDFIHVIqQGKtgNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAG-LPELTSVKD--IQYLKDSLALGKS 950
Cdd:cd05168   181 PFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNLT 257

                         250       260
                  ....*....|....*....|....*.
gi 1597423504 951 EEealkQFKQKFDEALRES---WTTK 973
Cdd:cd05168   258 EE----ECAQFVDSLIDKSlnnWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 687-925 3.74e-45

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: 162.12  E-value: 3.74e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 687 ELYIEKCKYMDSKMKPLWLvynnKVFGEDSV--GVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDH 764
Cdd:cd00142     2 ALDVGILKVIHSKQRPKKI----TLIGADGKtySFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSEN 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 765 SGLIEVVSTSETIADiqlnssnvaaaaafnkdaLLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIM 843
Cdd:cd00142    78 SGLIEIVKDAQTIED------------------LLKSLWRKSpSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIM 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 844 VKKTGQLFHIDFGHILGNFKSKfgIKRERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFAL 923
Cdd:cd00142   140 IEPSGNIFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAM-----GTAGVNGPFQISMVKIMEILREHADLIVPILEH 212


                  ..
gi 1597423504 924 ML 925
Cdd:cd00142   213 SL 214
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 124-232 7.44e-44

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: 154.02  E-value: 7.44e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  124 HEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKINELAIQKRLTIHGKEDEVSPyDYVLQVSGRVEYVFG 203
Cdd:smart00144   1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                           90       100
                   ....*....|....*....|....*....
gi 1597423504  204 DHPLIQFQYIRNCVMNRTLPHFILVECCK 232
Cdd:smart00144  80 DHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 482-600 2.39e-40

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: 145.82  E-value: 2.39e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 482 LKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 561
Cdd:cd00864     7 LLAILLYPPFSTLTEEEKELLWKFRYYLL-NVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSPKYPDP 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1597423504 562 YVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVH 600
Cdd:cd00864    86 VVRQYAVRVLESAsddelllylpqlvqalkyepyldsylaRFLLERALKSQRLGHQLYWNLKSEIH 151
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 124-232 7.02e-38

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: 137.04  E-value: 7.02e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 124 HEPSIPENLEdKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKINELAIQKRLTIHGKEDEVSpyDYVLQVSGRVEYVFG 203
Cdd:pfam00794   1 ASTVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLG 77

                          90       100
                  ....*....|....*....|....*....
gi 1597423504 204 DHPLIQFQYIRNCVMNRTLPHFILVECCK 232
Cdd:pfam00794  78 DHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 268-441 1.04e-35

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: 132.87  E-value: 1.04e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 268 SHVWENNNPFQIVLVKGNKLN--TEETVKVHVRAGLFHGTELLCKTIVSSEISGKNDHIWNEPLEFDINTCDLPRMARLC 345
Cdd:cd08380     1 KSLWDINFNLRIKIHGITNINllDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 346 FAVYAVLDKVKTKkstkainpskyqtirksgkvDYPVAWVNTMVFYFKGQLRSGDIILHSWSSFPDEleemlNPMGTVQT 425
Cdd:cd08380    81 LSIYAVSEPGSKK--------------------EVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPC 135

                         170
                  ....*....|....*.
gi 1597423504 426 NPYTENATALHIRFPE 441
Cdd:cd08380   136 NNSNENSTRLLIELPE 151
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
624-971 6.29e-35

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 145.31  E-value: 6.29e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  624 KALSKQVEALNK-----LKTLNSLIKLNAMKLNRAKGKEAMHTCLKQnAYREALSDLQSPLNPCVILSELYIEKCKYMDS 698
Cdd:COG5032   1701 KKFKIDISLLNLsrklyISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKS 1779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  699 -KMKPlwlvynNKVFGEDSVG----VIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDHSGLIE 769
Cdd:COG5032   1780 hLQRP------RRLTIRGSDGklysFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIE 1853

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  770 VVSTSETIADI------QLN-SSNVAAAAAFNKDALLNWLKEY-------------------NSGDDLD--RAIEEFTLS 821
Cdd:COG5032   1854 WVPNSDTLHSIlreyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARS 1933

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  822 CAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFR 900
Cdd:COG5032   1934 LAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM-----GVSGVEGSFR 2007

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  901 QCCEDAYLILRRHGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRES 969
Cdd:COG5032   2008 ELCETAFRALRKNADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQ 2087


                   ..
gi 1597423504  970 WT 971
Cdd:COG5032   2088 AT 2089
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 265-361 6.24e-28

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 108.59  E-value: 6.24e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504  265 RIISHVWENNNPFQ--IVLVKGNKLNTEETV-KVHVRAGLFHGTELLCKTIVSSEISGKNDHIWNEPLEFDINTCDLPRM 341
Cdd:smart00142   1 VKIESLWDCDRNLVitIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                           90       100
                   ....*....|....*....|
gi 1597423504  342 ARLCFAVYAVLDKVKTKKST 361
Cdd:smart00142  81 ARLCITIYAVKNPSKGSEFG 100
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 1-62 1.37e-27

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 106.80  E-value: 1.37e-27
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1597423504    1 QMLWKQVHNYPMFNLLMEIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 62
Cdd:smart00143  17 HELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 720-925 4.42e-26

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: 107.36  E-value: 4.42e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 720 IFKNGDDLRQDMLTLQMLRLMD-LLWKEAGLDLRMLP---YGCLATGDHSGLIEVVSTSETIadiqlnssnvaaaaafnK 795
Cdd:cd05164    33 LVKGDDDLRKDERVMQLFQLLNtLLEKDKETRKRNLTirtYSVVPLSSQSGLIEWVDNTTTL-----------------K 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 796 DALLNWLKE-YNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGnfKSKFGIKRERV 873
Cdd:cd05164    96 PVLKKWFNEtFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFN--KGKTLPVPEIV 173

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1597423504 874 PFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALML 925
Cdd:cd05164   174 PFRLTRNIINGM-----GPTGVEGLFRKSCEQVLRVFRKHKDKLITFLDTFL 220
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
1-61 1.94e-24

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 97.59  E-value: 1.94e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1597423504   1 QMLWKQVHNYPMFNLLMEIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCD 61
Cdd:pfam02192  14 EELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 270-427 2.61e-23

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: 97.17  E-value: 2.61e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 270 VWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHGTELLCkTIVSSEISGKNDHIWNEPLEFDINTCDLPRMARLCFAVY 349
Cdd:cd08398     3 LWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLC-DNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCLSIC 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1597423504 350 AVldkvktKKstkainpskyqtiRKSGKVDY-PVAWVNTMVFYFKGQLRSGDIILHSWsSFPDELEEMLNPMGTVQTNP 427
Cdd:cd08398    82 SV------KG-------------RKGAKEEHcPLAWGNINLFDYTDTLVSGKMALNLW-PVPHGLEDLLNPIGVTGSNP 140
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 720-920 2.32e-22

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: 98.38  E-value: 2.32e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 720 IFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDHSGLIEVVSTSETIADIQLNSSN--------- 786
Cdd:cd05171    33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSksgaharyr 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 787 ------------VAAAAAFNKDALLNWLKE----------------YNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRH 838
Cdd:cd05171   113 pkdwtastcrkkMREKAKASAEERLKVFDEicknfkpvfrhfflekFPDPSDWFERRLAYTRSVATSSIVGYILGLGDRH 192

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 839 SDNIMV-KKTGQLFHIDFGHILGnfkskFGiKR----ERVPFILTYDFIHVIqqGKTGnTEkfGRFRQCCEDAYLILRRH 913
Cdd:cd05171   193 LNNILIdQKTGELVHIDLGIAFE-----QG-KLlpipETVPFRLTRDIVDGM--GITG-VE--GVFRRCCEETLRVLREN 261


                  ....*..
gi 1597423504 914 GNLFITL 920
Cdd:cd05171   262 KEALLTI 268
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 691-913 2.81e-19

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: 87.95  E-value: 2.81e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 691 EKCKYMDSKMKPLWLVynnkVFGEDSVGVIF--KNGDDLRQDMltlqmlRLMD-------LLWKEAGLDLRMLP---YGC 758
Cdd:cd00892     6 DEVEIMPSLQKPKKIT----LVGSDGKKYPFlcKPKDDLRKDA------RMMEfntlinrLLSKDPESRRRNLHirtYAV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 759 LATGDHSGLIEVVSTSETIADIqlnssnvaaAAAFNKDALLNW-LKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDR 837
Cdd:cd00892    76 IPLNEECGIIEWVPNTVTLRSI---------LSTLYPPVLHEWfLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDR 146

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1597423504 838 HSDNIMV-KKTGQLFHIDFGHILGNFKsKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQCCEDAYLILRRH 913
Cdd:cd00892   147 HGENILFdSTTGDVVHVDFDCLFDKGL-TLEVP-ERVPFRLTQNMVDAM--GVTG-VE--GTFRRTCEVTLRVLREN 216
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 720-886 1.70e-18

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: 85.70  E-value: 1.70e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 720 IFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDHSGLIEVVSTSETIADIqlnssnvaaaaaFNK 795
Cdd:cd05172    33 LVKGGEDLRQDQRIQQLFDVMNNILASdpacRQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEI------------LEN 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 796 DALLNWLKEYNSGDDLDRAIE-EFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERV 873
Cdd:cd05172   101 DLLRRALLSLASSPEAFLALRsNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGHAFGSATQFLPIP-ELV 179

                         170
                  ....*....|...
gi 1597423504 874 PFILTYDFIHVIQ 886
Cdd:cd05172   180 PFRLTRQLLNLLQ 192
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 710-927 4.00e-18

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: 85.61  E-value: 4.00e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 710 KVFGEDSVGVIF--KNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDHSGLIEVVSTSETIA----- 778
Cdd:cd05169    21 TIVGSDGKEYKFllKGHEDLRLDERVMQLFGLVNTLLKNdsetSRRNLSIQRYSVIPLSPNSGLIGWVPGCDTLHslird 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 779 -----DIQLN-SSNVAAAAAFNKDAL--------LNWLKEYNSGDDLDRAI-------EE-------FTLSCAGYCVASY 830
Cdd:cd05169   101 yrekrKIPLNiEHRLMLQMAPDYDNLtliqkvevFEYALENTPGDDLRRVLwlkspssEAwlerrtnFTRSLAVMSMVGY 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 831 VLGIGDRHSDNIMV-KKTGQLFHIDFG-------HilgnfKSKFgikRERVPFILTYDFIHVIQQGKTGntekfGRFRQC 902
Cdd:cd05169   181 ILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRMLVNAMEVSGVE-----GTFRST 247

                         250       260
                  ....*....|....*....|....*
gi 1597423504 903 CEDAYLILRRHGNlfiTLFAlMLTA 927
Cdd:cd05169   248 CEDVMRVLRENKD---SLMA-VLEA 268
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 294-415 7.33e-16

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: 75.10  E-value: 7.33e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 294 KVHVRAGLFHGTELLCKTIVSSEISGKNDHI-WNEPLEFDINTCDLPRMARLCFAVYAVLDKVKTKKstkainpskyqti 372
Cdd:pfam00792   4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFV------------- 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1597423504 373 rksgkvdyPVAWVNTMVFYFKGQLRSGDIILHSWSSFPDELEE 415
Cdd:pfam00792  71 --------PIGWVNTSLFDKKGILRQGKQKLRLWPSKSTPGRS 105
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 296-441 1.03e-15

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: 75.86  E-value: 1.03e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 296 HVRAGLFHGTELLCKTIVSSEISGKNDH----IWNEPLEFDINTCDLPRMARLCFAVYAVLDkvktkkstkaiNPSKYQT 371
Cdd:cd04012    32 YLSCSLYHGGRLLCSPVTTKPVKITKSFfprvVWDEWIEFPIPVCQLPRESRLVLTLYGTTS-----------SPDGGSN 100

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 372 IRKSGKVdyPVAWVNTMVFYFKGQLRSGDIILHSWSSFPDeleEMLNPMGTvqTNPYTENATALHIRFPE 441
Cdd:cd04012   101 KQRMGPE--ELGWVSLPLFDFRGVLRQGSLLLGLWPPSKD---NPLGPAPP--PLFEQPDRVILQIDFPS 163
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 482-614 1.57e-15

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: 75.19  E-value: 1.57e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 482 LKEILDRDPLSQLCENEMDLIWTLRQDCrENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 561
Cdd:cd00869     7 LLDLIQKQSTYTLSTEDKDLLWEKRLYC-TNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPKFPDQ 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 562 YVREYAVGCLQQM---------------------------RFLLERALANRRIGQFLFWHLRSEVHIPAVSVQFGVILEA 614
Cdd:cd00869    86 EVRAHAVQWLARLsndelldylpqlvqalkfelylksalvRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQDLGAA 165
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 482-600 1.17e-14

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: 72.75  E-value: 1.17e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 482 LKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 561
Cdd:cd00870    14 LNKILKYPPTTKLTDEEKDLIWKFRFYLT-NNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELLSPYFTNP 92

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1597423504 562 YVREYAVGCLQQ----------------------------------MRFLLERALANRRIGQFLFWHLRSEVH 600
Cdd:cd00870    93 VVRKYAVSRLKLasdeelllyllqlvqalkyenldlsplprldsplADFLIERALKNPKLANFLYWYLKVELE 165
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 813-921 6.00e-14

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: 73.83  E-value: 6.00e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 813 RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVK-KTGQLFHIDF------GHILgnfkskfgikR--ERVPFILTYDFIH 883
Cdd:cd05170   189 RVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLTQNIEH 258

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1597423504 884 VIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLF 921
Cdd:cd05170   259 AL-----GPTGVEGTFRLSCEQVLKILRKGRETLLTLL 291
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 270-437 2.72e-12

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: 66.09  E-value: 2.72e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 270 VWENNNPFQIVLVKGNKL----NTEETVkvHVRAGLFHGTELLCKTIVSSEiSGKNDHIWNEPLEFDINTCDLPRMARLC 345
Cdd:cd08399     5 LWDCDRKFRVKILGIDIPvlprNTDLTV--FVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGALLN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 346 FAVYAV----LDKVKTKKSTKAINPSKYQTIRksgkvdypvaWVNTMVFYFKGQLRSGDIILHSWS-SFPDELEEMLNP- 419
Cdd:cd08399    82 LQIYCGkapaLSSKKSAESPSSESKGKHQLLY----------YVNLLLIDHRFLLRTGEYVLHMWQiSGKGEDQGSVNAd 151

                         170
                  ....*....|....*...
gi 1597423504 420 MGTVQTNPYTENATALHI 437
Cdd:cd08399   152 KLTSATNPDKENSMSISI 169
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 716-856 8.62e-09

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


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 55.14  E-value: 8.62e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 716 SVGVIFKNGDDlRQDMLTLQMLRLMDLLWKEAGLDLrmLPYGCLATGDHSG----LIEVVSTSETIADIQLNSsnvaaaa 791
Cdd:cd13968    18 TIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELVKGGTLIAYTQEEE------- 87

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1597423504 792 afnkdallnwLKEynsgddldRAIEEFTLSCAGYCVA--SYVLGIGDRHSDNIMVKKTGQLFHIDFG 856
Cdd:cd13968    88 ----------LDE--------KDVESIMYQLAECMRLlhSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 794-878 1.17e-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: 41.74  E-value: 1.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 794 NKDALLNW-LKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKRE 871
Cdd:cd05163   116 PETILSNYfLRTMPSPSDLWLFRKQFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDFLPSINSQGPLLDNNEP 195


                  ....*..
gi 1597423504 872 rVPFILT 878
Cdd:cd05163   196 -VPFRLT 201
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 297-406 2.35e-03

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


Pssm-ID: 176042  Cd Length: 159  Bit Score: 39.54  E-value: 2.35e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1597423504 297 VRAGLFHGTELLCKTIVSSEISGKNDHIWNEPLEFDINTCDLPRMARLCFAVYavlDKVKTKKSTkainpskyqtirksg 376
Cdd:cd08397    34 VTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIW---DVSGTGKAV--------------- 95

                          90       100       110
                  ....*....|....*....|....*....|
gi 1597423504 377 kvdyPVAWVNTMVFYFKGQLRSGDIILHSW 406
Cdd:cd08397    96 ----PFGGTTLSLFNKDGTLRRGRQKLRVW 121
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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