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Conserved domains on  [gi|157818713|ref|NP_001100291|]
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serine-protein kinase ATM [Rattus norvegicus]

Protein Classification

serine-protein kinase ATM( domain architecture ID 12110629)

serine-protein kinase ATM is recruited and activated by DNA double-strand breaks; it phosphorylates key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 2691-2970 0e+00

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: 580.65  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2691 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQ 2770
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2771 RSGVLEWCTGTIPIGEYLVNN--EEGAHKRYRPNDLSANQCQKKMMEVQKKSFEEKYETFMTICQNFEPVFRYFCMEKFL 2848
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVGAssKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2849 DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGI 2928
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 157818713 2929 TGVEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDWTM 2970
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2103-2497 1.19e-64

FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.


:

Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 224.54  E-value: 1.19e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2103 QELHYQAAWRNMQWDLCTSANQELEGTSYHESLYNALQCLRNREFSTFYDSLRHARVKEVEELSKGSLESVYSLYPTLSR 2182
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2183 LQAVGELENSGELFSRSVTDRERSEVYLK-WQKHSQLLKDsDFSFQEPLMALRTVILEILVQKEMensqggcsKDILTKH 2261
Cdd:pfam02259   81 LQQLAELEEIIQYKQKLGQSSEELKSLLQtWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYL--------GGYHAEM 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2262 LVEFSVLARTFKNTQLPERAIFKIKQYNPAICGIsEWHLEEAQVFWAKKEQSLALSILKQMIKKLDSSfrevcNEAGLKG 2341
Cdd:pfam02259  152 WLKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSCYLQK-----NGELLSG 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2342 LHAEClrvcgnwlAETCLENPAVIMQTYLEKAVKVAGSYDGDSRELRNGQMKAFLSLARFSDTQYQrIENYMKSSEFENK 2421
Cdd:pfam02259  226 LEVIN--------PTNLEEFTELLARCYLLKGKWQAALGQNWAEEKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVL 296

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157818713  2422 QALLKRAKEEVglirehkiqtnrytikvqreleldecalralKEDRKRFLCKAVENYISCLLSGEEHDL-WVFRLCS 2497
Cdd:pfam02259  297 RKEEQGKEEEG-------------------------------PEDLSRYVVPAVEGYLRSLSLSSENSLqDTLRLLT 342
TAN pfam11640
Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, ...
 8-165 2.48e-20

Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, critical for responding to DNA double-strand breaks (DSBs). Tel1, the orthologue from budding yeast, also regulates responses to DSBs. Tel1 is important for maintaining viability and for phosphorylation of the DNA damage signal transducer kinase Rad53 (an orthologue of mammalian CHK2). In addition to functioning in the response to DSBs, numerous findings indicate that Tel1/ATM regulates telomeres. The overall domain structure of Tel1/ATM is shared by proteins of the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family, but this family carries a unique and functionally important TAN sequence motif, near its N-terminal, LxxxKxxE/DRxxxL. which is conserved specifically in the Tel1/ATM subclass of the PIKKs. The TAN motif is essential for both telomere length maintenance and Tel1 action in response to DNA damage. It is classified as an EC:2.7.11.1.


:

Pssm-ID: 463317  Cd Length: 150  Bit Score: 90.07  E-value: 2.48e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713     8 LLICCRQLEHDRATERRKEVDKFKRLIQDPETVQhlDRHSDSKQgkylnWDAVFRFLQKYIQKETESLRTAKSnvSASTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSNRNKS--LSALNDKA-----WHSIFEALFRLIEAEKSAYLKAKK--SSTSK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713    88 TSRQKKMQEISSLVRFFIKCANKrapRLKcQDLLNYVMDTVKDSSNGAT------YGADCSNIlLKDILSVRKYWCEVSQ 161
Cdd:pfam11640   72 SAAARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLLPLPDgellepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 157818713   162 QQWL 165
Cdd:pfam11640  147 EDWI 150
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 3034-3063 1.50e-10

FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution structure of the FATC domain suggests it plays a role in redox-dependent structural and cellular stability.


:

Pssm-ID: 460514 [Multi-domain]  Cd Length: 32  Bit Score: 58.16  E-value: 1.50e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 157818713  3034 LSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3063
Cdd:pfam02260    2 LSVEGQVDELIQEATDPENLAQMYIGWCPW 31
 
Name Accession Description Interval E-value
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 2691-2970 0e+00

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: 580.65  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2691 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQ 2770
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2771 RSGVLEWCTGTIPIGEYLVNN--EEGAHKRYRPNDLSANQCQKKMMEVQKKSFEEKYETFMTICQNFEPVFRYFCMEKFL 2848
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVGAssKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2849 DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGI 2928
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 157818713 2929 TGVEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDWTM 2970
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2723-2972 2.28e-80

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


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 265.70  E-value: 2.28e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713   2723 LVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTIPIGEYLVNNEEGAHKRYRPn 2802
Cdd:smart00146    2 IFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL- 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713   2803 dlsanqcqkkmMEVQKKSFEEKYETFMTICQNFEPVFRYFCMEKFLDPA-VWFEKRLAYTRSVATSSIVGYILGLGDRHV 2881
Cdd:smart00146   81 -----------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPSeDYFEARKNFTRSCAGYSVITYILGLGDRHN 149

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713   2882 QNILINEqSAELVHIDLGVAFEQGKILPTP-ETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQEALLTIVEVL 2960
Cdd:smart00146  150 DNIMLDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELM 228

                           250
                    ....*....|..
gi 157818713   2961 LYDPLFDWTMNP 2972
Cdd:smart00146  229 LYDGLPDWRSGK 240
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2543-3063 1.57e-74

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 278.20  E-value: 1.57e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2543 LGFHEVLNNLISRISMDHPhhtlFIILALANankDEFLskpETARRGRITKNAPKESSQLDEDRAEAASRiihtiRSARR 2622
Cdd:COG5032  1637 LLFEPILAQLLSRLSSENN----KISVALLI---DKPL---HEERENFPSGLSLSSFQSSFLKELIKKSP-----RKIRK 1701

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2623 TMVKDMEALCDAYIILANlDASQWRNQRKGIsipanqpITKLKNLEDVV---VPTMEIKVDPtGEYEK---LVTIKSFKT 2696
Cdd:COG5032  1702 KFKIDISLLNLSRKLYIS-VLRSIRKRLKRL-------LELRLKKVSPKlllFHAFLEIKLP-GQYLLdkpFVLIERFEP 1772

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2697 EFRLA-GGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQRSGVL 2775
Cdd:COG5032  1773 EVSVVkSHLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKVIPLSPGSGII 1852

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2776 EWCTGTIPIGEYLvnneEGAHKRYRPndlSANQCQKKMMEVQKKSFEEKYETFMTICQNFEPVFRYFCMEKFLDPAVWFE 2855
Cdd:COG5032  1853 EWVPNSDTLHSIL----REYHKRKNI---SIDQEKKLAARLDNLKLLLKDEFFTKATLKSPPVLYDWFSESFPNPEDWLT 1925

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2856 KRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLG-VAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGV 2934
Cdd:COG5032  1926 ARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGfILFNAPGRFPFPEKVPFRLTRNIVEAMGVSGVEGS 2005

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2935 FRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDWTMNPlkalylqqrpedetdlqstpsaddqeckrslsDTDQSFNKVA 3014
Cdd:COG5032  2006 FRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLP--------------------------------CFREIQNNEI 2053

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|.
gi 157818713 3015 ERVLMRLQEKLKG--VEEGTVLSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3063
Cdd:COG5032  2054 VNVLERFRLKLSEkdAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPF 2104
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2103-2497 1.19e-64

FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 224.54  E-value: 1.19e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2103 QELHYQAAWRNMQWDLCTSANQELEGTSYHESLYNALQCLRNREFSTFYDSLRHARVKEVEELSKGSLESVYSLYPTLSR 2182
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2183 LQAVGELENSGELFSRSVTDRERSEVYLK-WQKHSQLLKDsDFSFQEPLMALRTVILEILVQKEMensqggcsKDILTKH 2261
Cdd:pfam02259   81 LQQLAELEEIIQYKQKLGQSSEELKSLLQtWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYL--------GGYHAEM 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2262 LVEFSVLARTFKNTQLPERAIFKIKQYNPAICGIsEWHLEEAQVFWAKKEQSLALSILKQMIKKLDSSfrevcNEAGLKG 2341
Cdd:pfam02259  152 WLKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSCYLQK-----NGELLSG 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2342 LHAEClrvcgnwlAETCLENPAVIMQTYLEKAVKVAGSYDGDSRELRNGQMKAFLSLARFSDTQYQrIENYMKSSEFENK 2421
Cdd:pfam02259  226 LEVIN--------PTNLEEFTELLARCYLLKGKWQAALGQNWAEEKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVL 296

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157818713  2422 QALLKRAKEEVglirehkiqtnrytikvqreleldecalralKEDRKRFLCKAVENYISCLLSGEEHDL-WVFRLCS 2497
Cdd:pfam02259  297 RKEEQGKEEEG-------------------------------PEDLSRYVVPAVEGYLRSLSLSSENSLqDTLRLLT 342
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 2723-2970 4.88e-57

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: 198.71  E-value: 4.88e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2723 LVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRkltICTYKVVPLSQRSGVLEWctgtipigeylVNNEEGAHK---RY 2799
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEW-----------VPNSETLAYildEY 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2800 RPNDLSANQCQKKM-----MEVQKKSFEEKYETFMTIcqnfePVFRYFcMEKFLDPAVWFEKRLAYTRSVATSSIVGYIL 2874
Cdd:pfam00454   71 GENGVPPTAMVKILhsalnYPKLKLEFESRISLPPKV-----GLLQWF-VKKSPDAEEWGEARKNFVRSCAGYSVLDYIL 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2875 GLGDRHVQNILINEQSAELVHIDLGVAF-EQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQEAL 2953
Cdd:pfam00454  145 GNGDRHLDNILVDKTTGKLFHIDFGLCLpDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLL 224

                          250
                   ....*....|....*..
gi 157818713  2954 LTIVEVLLYDPLFDWTM 2970
Cdd:pfam00454  225 TNLLKLMVADGLPDWSI 241
TAN pfam11640
Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, ...
 8-165 2.48e-20

Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, critical for responding to DNA double-strand breaks (DSBs). Tel1, the orthologue from budding yeast, also regulates responses to DSBs. Tel1 is important for maintaining viability and for phosphorylation of the DNA damage signal transducer kinase Rad53 (an orthologue of mammalian CHK2). In addition to functioning in the response to DSBs, numerous findings indicate that Tel1/ATM regulates telomeres. The overall domain structure of Tel1/ATM is shared by proteins of the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family, but this family carries a unique and functionally important TAN sequence motif, near its N-terminal, LxxxKxxE/DRxxxL. which is conserved specifically in the Tel1/ATM subclass of the PIKKs. The TAN motif is essential for both telomere length maintenance and Tel1 action in response to DNA damage. It is classified as an EC:2.7.11.1.


Pssm-ID: 463317  Cd Length: 150  Bit Score: 90.07  E-value: 2.48e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713     8 LLICCRQLEHDRATERRKEVDKFKRLIQDPETVQhlDRHSDSKQgkylnWDAVFRFLQKYIQKETESLRTAKSnvSASTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSNRNKS--LSALNDKA-----WHSIFEALFRLIEAEKSAYLKAKK--SSTSK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713    88 TSRQKKMQEISSLVRFFIKCANKrapRLKcQDLLNYVMDTVKDSSNGAT------YGADCSNIlLKDILSVRKYWCEVSQ 161
Cdd:pfam11640   72 SAAARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLLPLPDgellepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 157818713   162 QQWL 165
Cdd:pfam11640  147 EDWI 150
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 3034-3063 1.50e-10

FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution structure of the FATC domain suggests it plays a role in redox-dependent structural and cellular stability.


Pssm-ID: 460514 [Multi-domain]  Cd Length: 32  Bit Score: 58.16  E-value: 1.50e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 157818713  3034 LSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3063
Cdd:pfam02260    2 LSVEGQVDELIQEATDPENLAQMYIGWCPW 31
 
Name Accession Description Interval E-value
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 2691-2970 0e+00

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: 580.65  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2691 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQ 2770
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2771 RSGVLEWCTGTIPIGEYLVNN--EEGAHKRYRPNDLSANQCQKKMMEVQKKSFEEKYETFMTICQNFEPVFRYFCMEKFL 2848
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVGAssKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2849 DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGI 2928
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 157818713 2929 TGVEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDWTM 2970
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 2691-2963 1.07e-95

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: 308.82  E-value: 1.07e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2691 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQ 2770
Cdd:cd05164     1 IASFDPRVRILASLQKPKKITILGSDGKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKETRKRNLTIRTYSVVPLSS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2771 RSGVLEWCTGTIPIGeylvnneegahkryrpndlsanqcqkkmmevqkksfeekyetfmticqnfePVFRYFCMEKFLDP 2850
Cdd:cd05164    81 QSGLIEWVDNTTTLK---------------------------------------------------PVLKKWFNETFPDP 109

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2851 AVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITG 2930
Cdd:cd05164   110 TQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIDTKTGEVVHIDFGMIFNKGKTLPVPEIVPFRLTRNIINGMGPTG 189

                         250       260       270
                  ....*....|....*....|....*....|...
gi 157818713 2931 VEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYD 2963
Cdd:cd05164   190 VEGLFRKSCEQVLRVFRKHKDKLITFLDTFLYD 222
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 2691-2969 1.50e-83

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: 274.77  E-value: 1.50e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2691 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQ 2770
Cdd:cd00892     1 ISGFEDEVEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2771 RSGVLEWCTGTIPIGEYLVnneegahkRYRPndlsanqcqkkmmevqkksfeekyetfmticqnfePVFRYFCMEKFLDP 2850
Cdd:cd00892    81 ECGIIEWVPNTVTLRSILS--------TLYP-----------------------------------PVLHEWFLKNFPDP 117

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2851 AVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITG 2930
Cdd:cd00892   118 TAWYEARNNYTRSTAVMSMVGYILGLGDRHGENILFDSTTGDVVHVDFDCLFDKGLTLEVPERVPFRLTQNMVDAMGVTG 197

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 157818713 2931 VEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDWT 2969
Cdd:cd00892   198 VEGTFRRTCEVTLRVLRENRETLMSVLETFVHDPLVEWS 236
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2723-2972 2.28e-80

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


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 265.70  E-value: 2.28e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713   2723 LVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTIPIGEYLVNNEEGAHKRYRPn 2802
Cdd:smart00146    2 IFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL- 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713   2803 dlsanqcqkkmMEVQKKSFEEKYETFMTICQNFEPVFRYFCMEKFLDPA-VWFEKRLAYTRSVATSSIVGYILGLGDRHV 2881
Cdd:smart00146   81 -----------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPSeDYFEARKNFTRSCAGYSVITYILGLGDRHN 149

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713   2882 QNILINEqSAELVHIDLGVAFEQGKILPTP-ETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQEALLTIVEVL 2960
Cdd:smart00146  150 DNIMLDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELM 228

                           250
                    ....*....|..
gi 157818713   2961 LYDPLFDWTMNP 2972
Cdd:smart00146  229 LYDGLPDWRSGK 240
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2543-3063 1.57e-74

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 278.20  E-value: 1.57e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2543 LGFHEVLNNLISRISMDHPhhtlFIILALANankDEFLskpETARRGRITKNAPKESSQLDEDRAEAASRiihtiRSARR 2622
Cdd:COG5032  1637 LLFEPILAQLLSRLSSENN----KISVALLI---DKPL---HEERENFPSGLSLSSFQSSFLKELIKKSP-----RKIRK 1701

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2623 TMVKDMEALCDAYIILANlDASQWRNQRKGIsipanqpITKLKNLEDVV---VPTMEIKVDPtGEYEK---LVTIKSFKT 2696
Cdd:COG5032  1702 KFKIDISLLNLSRKLYIS-VLRSIRKRLKRL-------LELRLKKVSPKlllFHAFLEIKLP-GQYLLdkpFVLIERFEP 1772

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2697 EFRLA-GGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQRSGVL 2775
Cdd:COG5032  1773 EVSVVkSHLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKVIPLSPGSGII 1852

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2776 EWCTGTIPIGEYLvnneEGAHKRYRPndlSANQCQKKMMEVQKKSFEEKYETFMTICQNFEPVFRYFCMEKFLDPAVWFE 2855
Cdd:COG5032  1853 EWVPNSDTLHSIL----REYHKRKNI---SIDQEKKLAARLDNLKLLLKDEFFTKATLKSPPVLYDWFSESFPNPEDWLT 1925

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2856 KRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLG-VAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGV 2934
Cdd:COG5032  1926 ARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGfILFNAPGRFPFPEKVPFRLTRNIVEAMGVSGVEGS 2005

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2935 FRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDWTMNPlkalylqqrpedetdlqstpsaddqeckrslsDTDQSFNKVA 3014
Cdd:COG5032  2006 FRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLP--------------------------------CFREIQNNEI 2053

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|.
gi 157818713 3015 ERVLMRLQEKLKG--VEEGTVLSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3063
Cdd:COG5032  2054 VNVLERFRLKLSEkdAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPF 2104
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 2691-2968 3.49e-70

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: 238.15  E-value: 3.49e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2691 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDA-VMQqVFQMCNMLLQRNTETRKRKLTICTYKVVPLS 2769
Cdd:cd05169     1 ISSFDPTLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDErVMQ-LFGLVNTLLKNDSETSRRNLSIQRYSVIPLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2770 QRSGVLEWCTGTIPIGEyLVnneegahKRYRPNDLSANQCQKKMMEVQKKSFEEkyetfMTICQNFEpVFRYFC------ 2843
Cdd:cd05169    80 PNSGLIGWVPGCDTLHS-LI-------RDYREKRKIPLNIEHRLMLQMAPDYDN-----LTLIQKVE-VFEYALentpgd 145

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2844 -MEKFL-----DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPT-PETVPF 2916
Cdd:cd05169   146 dLRRVLwlkspSSEAWLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLTGKVIHIDFGDCFEVAMHREKfPEKVPF 225

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 157818713 2917 RLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDW 2968
Cdd:cd05169   226 RLTRMLVNAMEVSGVEGTFRSTCEDVMRVLRENKDSLMAVLEAFVHDPLISW 277
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 2689-2969 7.73e-69

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: 235.23  E-value: 7.73e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2689 VTIKSFKTEfrlagglnlPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPL 2768
Cdd:cd05170     8 VTVLPTKTK---------PKKLVFLGSDGKRYPYLFKGLEDLHLDERIMQFLSIVNAMLASDNEHRRRRYRARHYSVTPL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2769 SQRSGVLEWCTGTIPI----------GEYL------VNNEEGAHKRyRPNDLSANQCQKKM---------------MEVQ 2817
Cdd:cd05170    79 GPRSGLIQWVDGATPLfslykrwqqrRAAAqaqknqDSGSTPPPVP-RPSELFYNKLKPALkaagirkstsrrewpLEVL 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2818 KKSFEE-KYETFMTICQNfepvfRYFCMEkfLDPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHI 2896
Cdd:cd05170   158 RQVLEElVAETPRDLLAR-----ELWCSS--PSSAEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDLSTGEVVHI 230

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 157818713 2897 DLGVAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDWT 2969
Cdd:cd05170   231 DYNVCFEKGKRLRVPEKVPFRLTQNIEHALGPTGVEGTFRLSCEQVLKILRKGRETLLTLLEAFVYDPLVDWT 303
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2103-2497 1.19e-64

FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 224.54  E-value: 1.19e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2103 QELHYQAAWRNMQWDLCTSANQELEGTSYHESLYNALQCLRNREFSTFYDSLRHARVKEVEELSKGSLESVYSLYPTLSR 2182
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2183 LQAVGELENSGELFSRSVTDRERSEVYLK-WQKHSQLLKDsDFSFQEPLMALRTVILEILVQKEMensqggcsKDILTKH 2261
Cdd:pfam02259   81 LQQLAELEEIIQYKQKLGQSSEELKSLLQtWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYL--------GGYHAEM 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2262 LVEFSVLARTFKNTQLPERAIFKIKQYNPAICGIsEWHLEEAQVFWAKKEQSLALSILKQMIKKLDSSfrevcNEAGLKG 2341
Cdd:pfam02259  152 WLKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSCYLQK-----NGELLSG 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2342 LHAEClrvcgnwlAETCLENPAVIMQTYLEKAVKVAGSYDGDSRELRNGQMKAFLSLARFSDTQYQrIENYMKSSEFENK 2421
Cdd:pfam02259  226 LEVIN--------PTNLEEFTELLARCYLLKGKWQAALGQNWAEEKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVL 296

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157818713  2422 QALLKRAKEEVglirehkiqtnrytikvqreleldecalralKEDRKRFLCKAVENYISCLLSGEEHDL-WVFRLCS 2497
Cdd:pfam02259  297 RKEEQGKEEEG-------------------------------PEDLSRYVVPAVEGYLRSLSLSSENSLqDTLRLLT 342
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 2691-2968 1.92e-59

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: 205.50  E-value: 1.92e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2691 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRKLTICTYKVVPLSQ 2770
Cdd:cd05172     1 IVGFDPRVLVLSSKRRPKRITIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDPACRQRRLRIRTYQVIPMTS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2771 RSGVLEWCTGTIPIGEYLVNNeegahkryrpndlsanqcqkkmmevqkksfeekyetfmticqnfepVFRYFCMEKFLDP 2850
Cdd:cd05172    81 RLGLIEWVDNTTPLKEILEND----------------------------------------------LLRRALLSLASSP 114

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2851 AVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQG-KILPTPETVPFRLSRDIVDGMGIT 2929
Cdd:cd05172   115 EAFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVDLSTGRLIGIDFGHAFGSAtQFLPIPELVPFRLTRQLLNLLQPL 194

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 157818713 2930 GVEGVFRRCCEKTMEVMRSSQEALLTIVEVLLYDPLFDW 2968
Cdd:cd05172   195 DARGLLRSDMVHVLRALRAGRDLLLATMDVFVKEPLLDW 233
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 2723-2970 4.88e-57

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: 198.71  E-value: 4.88e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2723 LVKGRDDLRQDAVMQQVFQMCNMLLQRNTETRKRkltICTYKVVPLSQRSGVLEWctgtipigeylVNNEEGAHK---RY 2799
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEW-----------VPNSETLAYildEY 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2800 RPNDLSANQCQKKM-----MEVQKKSFEEKYETFMTIcqnfePVFRYFcMEKFLDPAVWFEKRLAYTRSVATSSIVGYIL 2874
Cdd:pfam00454   71 GENGVPPTAMVKILhsalnYPKLKLEFESRISLPPKV-----GLLQWF-VKKSPDAEEWGEARKNFVRSCAGYSVLDYIL 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713  2875 GLGDRHVQNILINEQSAELVHIDLGVAF-EQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQEAL 2953
Cdd:pfam00454  145 GNGDRHLDNILVDKTTGKLFHIDFGLCLpDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLL 224

                          250
                   ....*....|....*..
gi 157818713  2954 LTIVEVLLYDPLFDWTM 2970
Cdd:pfam00454  225 TNLLKLMVADGLPDWSI 241
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 2707-2963 1.10e-34

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: 133.61  E-value: 1.10e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2707 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFqmcnMLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTIPIge 2786
Cdd:cd00142    17 PKKITLIGADGKTYSFLLKRRDDLRKDERSFQFM----RLIQSILEKESVNLVLPPYKVIPLSENSGLIEIVKDAQTI-- 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2787 ylvnneegahkryrpndlsanqcqkkmmEVQKKSFEEKyetfmtiCQNFEpvfryfcmekfldpaVWFEKRLAYTRSVAT 2866
Cdd:cd00142    91 ----------------------------EDLLKSLWRK-------SPSSQ---------------SWLNRRENFSCSLAG 120

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2867 SSIVGYILGLGDRHVQNILINEqSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVM 2946
Cdd:cd00142   121 YSVLGYIFGIGDRHPSNIMIEP-SGNIFHIDFGFIFSGRKLAEGVETVPFRLTPMLENAMGTAGVNGPFQISMVKIMEIL 199

                         250
                  ....*....|....*..
gi 157818713 2947 RSSQEALLTIVEVLLYD 2963
Cdd:cd00142   200 REHADLIVPILEHSLRD 216
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2707-2940 5.46e-22

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: 100.30  E-value: 5.46e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2707 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNMLLQRntETRKRKLTicTYKVVPLSQRSGVLEWCTGTIPIGE 2786
Cdd:cd00896    80 PLKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKK--ENLDLKLT--PYKVLATSPNDGLVEFVPNSKALAD 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2787 YLvnneegahkryrpndlsanqcqkkmmevqkksfeEKYETFMTICQNFEPvfryfcmEKFLDPAVWFEKRLAYTRSVAT 2866
Cdd:cd00896   156 IL----------------------------------KKYGSILNFLRKHNP-------DESGPYGIKPEVMDNFVKSCAG 194

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2867 SSIVGYILGLGDRHVQNILINEqSAELVHIDLGvaFeqgkIL---PTPETVPFRLSRDIVDGMGITGVEG--VFRR-CCE 2940
Cdd:cd00896   195 YCVITYILGVGDRHLDNLLLTK-DGHLFHIDFG--Y----ILgrdPKPFPPPMKLCKEMVEAMGGANSEGykEFKKyCCT 267
TAN pfam11640
Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, ...
 8-165 2.48e-20

Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, critical for responding to DNA double-strand breaks (DSBs). Tel1, the orthologue from budding yeast, also regulates responses to DSBs. Tel1 is important for maintaining viability and for phosphorylation of the DNA damage signal transducer kinase Rad53 (an orthologue of mammalian CHK2). In addition to functioning in the response to DSBs, numerous findings indicate that Tel1/ATM regulates telomeres. The overall domain structure of Tel1/ATM is shared by proteins of the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family, but this family carries a unique and functionally important TAN sequence motif, near its N-terminal, LxxxKxxE/DRxxxL. which is conserved specifically in the Tel1/ATM subclass of the PIKKs. The TAN motif is essential for both telomere length maintenance and Tel1 action in response to DNA damage. It is classified as an EC:2.7.11.1.


Pssm-ID: 463317  Cd Length: 150  Bit Score: 90.07  E-value: 2.48e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713     8 LLICCRQLEHDRATERRKEVDKFKRLIQDPETVQhlDRHSDSKQgkylnWDAVFRFLQKYIQKETESLRTAKSnvSASTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSNRNKS--LSALNDKA-----WHSIFEALFRLIEAEKSAYLKAKK--SSTSK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713    88 TSRQKKMQEISSLVRFFIKCANKrapRLKcQDLLNYVMDTVKDSSNGAT------YGADCSNIlLKDILSVRKYWCEVSQ 161
Cdd:pfam11640   72 SAAARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLLPLPDgellepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 157818713   162 QQWL 165
Cdd:pfam11640  147 EDWI 150
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 2714-2935 2.30e-14

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: 75.64  E-value: 2.30e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2714 GSDGKERRQLVK---GRDDLRQDAVMQQvFQMCNMLLQRNTETRKRKLTICTYKVVPLSQrsgvlewctgtipigeylvn 2790
Cdd:cd05163    25 GHDGSKYPFLVQtpsARHSRREERVMQL-FRLLNRVLERKKETRRRNLQFHVPIVVPLSP-------------------- 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2791 neegaHKRYRPNDLSANqcqkkmmevqkkSFEEKYE---TFMTICQNFEP---VFRYFcMEKFLDP-AVW-FEKRLayTR 2862
Cdd:cd05163    84 -----QVRLVEDDPSYI------------SLQDIYEkleILNEIQSKMVPetiLSNYF-LRTMPSPsDLWlFRKQF--TL 143

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 157818713 2863 SVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKIL-PTPETVPFRLSRDIVDGMGITGVEGVF 2935
Cdd:cd05163   144 QLALSSFMTYVLSLGNRTPHRILISRSTGNVFMTDFLPSINSQGPLlDNNEPVPFRLTPNIQHFIGPIGVEGLL 217
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 2724-2981 4.66e-14

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: 75.38  E-value: 4.66e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2724 VKGRDDLRQDA-------VMQQVFQMCnmllqrntetrKRKLTICTYKVVPLSQRSGVLEWCtgtipigeylvnneegah 2796
Cdd:cd00893    32 VKTGDDLKQEQlalqlisQFDQIFKEE-----------GLPLWLRPYEILSLGPDSGIIEMI------------------ 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2797 kryrPNDLSANQCQKKMMEVQKKS-----FEEKYETfmticQNFEPVFRYFCmekfldpavwfekrlaytRSVATSSIVG 2871
Cdd:cd00893    83 ----KNAVSIDSLKKKLDSFNKFVslsdfFDDNFGD-----EAIQKARDNFL------------------QSLVAYSLVC 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2872 YILGLGDRHVQNILINEQsAELVHIDLGVAFEQgkilpTP-----ETVPFRLSRDIVDGMGITGVE--GVFRRCCEKTME 2944
Cdd:cd00893   136 YFLQIKDRHNGNILLDKE-GHIIHIDFGFFLSS-----HPgfygfEGAPFKLSSEYIEVLGGVDSElfKEFRKLFLKGFM 209

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 157818713 2945 VMRSSQEALLTIVEvLLYDPLFDWTMNPLKALYLQQR 2981
Cdd:cd00893   210 ALRKHSDKILSLVE-MMYSGHGITCFGKKTIQQLKQR 245
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 2724-2964 1.34e-13

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: 74.05  E-value: 1.34e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2724 VKGRDDLRQDAVMQQVFQMCNMLLQRntetRKRKLTICTYKVVPLSQRSGVLEWCTGTIPIgeylvnneegaH--KRYRP 2801
Cdd:cd05168    35 VKSGDDLRQELLAMQLIKQFQRIFEE----AGLPLWLRPYEILVTSSDSGLIETIPDTVSI-----------DslKKRFP 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2802 NDLSANQCqkkmmevqkksFEEKY-----ETFMTICQNFepvfryfcmekfldpavwfekrlayTRSVATSSIVGYILGL 2876
Cdd:cd05168   100 NFTSLLDY-----------FERTFgdpnsERFKEAQRNF-------------------------VESLAAYSLVCYLLQI 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2877 GDRHVQNILINEQsAELVHIDLG---------VAFeqgkilptpETVPFRLSRDIVDGMGitGVEG----VFRRCCEKTM 2943
Cdd:cd05168   144 KDRHNGNILLDSE-GHIIHIDFGfmlsnspggLGF---------ETAPFKLTQEYVEVMG--GLESdmfrYFKTLMIQGF 211

                         250       260
                  ....*....|....*....|.
gi 157818713 2944 EVMRSSQEALLTIVEVLLYDP 2964
Cdd:cd05168   212 LALRKHADRIVLLVEIMQQGS 232
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 2725-2962 3.30e-13

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: 73.40  E-value: 3.30e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2725 KGRDDLRQD-------AVMQQVFQMCNMllqrntetrkrKLTICTYKVVPLSQRSGVLEwctgtipigeyLVnneegahk 2797
Cdd:cd05167    55 KVGDDCRQDmlalqliSLFKNIFEEVGL-----------DLYLFPYRVVATGPGCGVIE-----------VI-------- 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2798 ryrPNDLSANQCQKkmmevqkksfeekyetfmticQNFEPVFRYFcMEKFLDP-AVWFEK-RLAYTRSVATSSIVGYILG 2875
Cdd:cd05167   105 ---PNSKSRDQIGR---------------------ETDNGLYEYF-LSKYGDEsTPAFQKaRRNFIKSMAGYSLVSYLLQ 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2876 LGDRHVQNILINEQsAELVHIDLGVAFEQ--GKILPTpETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVM---RSSQ 2950
Cdd:cd05167   160 IKDRHNGNIMIDDD-GHIIHIDFGFIFEIspGGNLGF-ESAPFKLTKEMVDLMGGSMESEPFKWFVELCVRGYlavRPYA 237

                         250
                  ....*....|..
gi 157818713 2951 EALLTIVEVLLY 2962
Cdd:cd05167   238 EAIVSLVELMLD 249
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 3034-3063 1.50e-10

FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution structure of the FATC domain suggests it plays a role in redox-dependent structural and cellular stability.


Pssm-ID: 460514 [Multi-domain]  Cd Length: 32  Bit Score: 58.16  E-value: 1.50e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 157818713  3034 LSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3063
Cdd:pfam02260    2 LSVEGQVDELIQEATDPENLAQMYIGWCPW 31
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 2723-2947 2.55e-09

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: 61.99  E-value: 2.55e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2723 LVKGRDDLRQDAVMQQVFQMCNMLLQrnteTRKRKLTICTYKVVPLSQRSGVLEWCTGTIPIGEYLVNNEEGAHKRYRPN 2802
Cdd:cd05174   101 IFKNGDDLRQDMLTLQMIQLMDVLWK----QEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQLNKSNMAATAAFNK 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2803 DLSANQCQKKMmevQKKSFEEKYETFMTICQNFepvfryfCmekfldpavwfekrlaytrsVATssivgYILGLGDRHVQ 2882
Cdd:cd05174   177 DALLNWLKSKN---PGDALDQAIEEFTLSCAGY-------C--------------------VAT-----YVLGIGDRHSD 221

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 157818713 2883 NILINEqSAELVHIDLG--VAFEQGKILPTPETVPFRLSRDIVDGM--GITGVEGVFRR---CCEKTMEVMR 2947
Cdd:cd05174   222 NIMIRE-SGQLFHIDFGhfLGNFKTKFGINRERVPFILTYDFVHVIqqGKTNNSEKFERfrgYCERAYTILR 292
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 2860-2961 3.69e-08

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: 58.43  E-value: 3.69e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2860 YTRSVATSSIVGYILGLGDRHVQNILInEQSAELVHIDLG--VAFEQGKILPTPETVPFRLSRDIVDGM--GITGVE--- 2932
Cdd:cd05173   196 FTLSCAGYCVATYVLGIGDRHSDNIMV-RKNGQLFHIDFGhiLGNFKSKFGIKRERVPFILTYDFIHVIqqGKTGNTekf 274

                          90       100
                  ....*....|....*....|....*....
gi 157818713 2933 GVFRRCCEKTMEVMRSSQEALLTIVEVLL 2961
Cdd:cd05173   275 GRFRQYCEDAYLILRKNGNLFITLFALML 303
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2728-2991 5.41e-07

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: 54.60  E-value: 5.41e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2728 DDLRQDA-VMQQVFQMCNMLLQRNTEtrkrkLTICTYKVVPLSQRSGVLEwctgtipigeyLVNNEEgahkryrpndlsa 2806
Cdd:cd05166    99 DDLRQDMlTLQLIRIMDKIWLQEGLD-----LKMITFRCVPTGNKRGMVE-----------LVPEAE------------- 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2807 nqcqkKMMEVQKK-----SFEEKyetfmTIcqnfepvfryfcmekfldpAVWFEK----RLAY-------TRSVATSSIV 2870
Cdd:cd05166   150 -----TLREIQTEhgltgSFKDR-----PL-------------------ADWLQKhnpsELEYekavenfIRSCAGYCVA 200

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2871 GYILGLGDRHVQNILInEQSAELVHIDLgvafeqGKILPTPET--------VPFRLSRD----IVDGMGITGVEGVFRRC 2938
Cdd:cd05166   201 TYVLGICDRHNDNIML-KTSGHLFHIDF------GKFLGDAQMfgnfkrdrVPFVLTSDmayvINGGDKPSSRFQLFVDL 273

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 157818713 2939 CEKTMEVMRSSQEALLTIVEVLLYDPLFDWTMNPLKALYLQQRPEDeTDLQST 2991
Cdd:cd05166   274 CCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQDDLRYVQDALLPEL-TDAEAT 325
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2860-2948 1.74e-05

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: 49.94  E-value: 1.74e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2860 YTRSVATSSIVGYILGLGDRHVQNILINEqSAELVHIDLgvafeqGKILP--------TPETVPFRLSRD----IVDGMG 2927
Cdd:cd05165   197 FTLSCAGYCVATYVLGIGDRHSDNIMVKE-NGQLFHIDF------GHFLGnfkkkfgiKRERVPFVLTHDfvyvIARGQD 269

                          90       100
                  ....*....|....*....|...
gi 157818713 2928 ITGVEGV--FRRCCEKTMEVMRS 2948
Cdd:cd05165   270 NTKSEEFqeFQELCEKAYLILRR 292
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2728-2939 3.72e-05

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: 48.72  E-value: 3.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2728 DDLRQDAVMQQVFQ-MCNMLLQRNTETRkrkLTIctYKVVplsqrsgvlewCTGtipigeylvnNEEGahkryrpndlsa 2806
Cdd:cd00891    96 DDLRQDQLTLQLLRiMDKLWKKEGLDLR---MTP--YKCI-----------ATG----------DEVG------------ 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2807 nqcqkkMMEVQKKSfeekyETFMTICQN---FEPVFRYFCMEKFL-----DPAVWFEKRLAYTRS-----VATssivgYI 2873
Cdd:cd00891   138 ------MIEVVPNS-----ETTAAIQKKyggFGAAFKDTPISNWLkkhnpTEEEYEEAVENFIRScagycVAT-----YV 201

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 157818713 2874 LGLGDRHVQNILINeQSAELVHIDlgvaFeqGKIL---PTP-----ETVPFRLSRDIVDGMGitGVEGV----FRRCC 2939
Cdd:cd00891   202 LGIGDRHNDNIMVT-KSGHLFHID----F--GHFLgnfKKKfgikrERAPFVFTPEMAYVMG--GEDSEnfqkFEDLC 270
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 2860-2961 8.12e-05

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: 47.94  E-value: 8.12e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157818713 2860 YTRSVATSSIVGYILGLGDRHVQNILINEQsAELVHIDLGVAFEQGKIL--PTPETVPFRLSRDIVDGMGITGVEGV--- 2934
Cdd:cd00894   200 FVYSCAGYCVATFVLGIGDRHNDNIMITET-GNLFHIDFGHILGNYKSFlgINKERVPFVLTPDFLFVMGTSGKKTSlhf 278

                          90       100
                  ....*....|....*....|....*....
gi 157818713 2935 --FRRCCEKTMEVMRSSQEALLTIVEVLL 2961
Cdd:cd00894   279 qkFQDVCVKAYLALRHHTNLLIILFSMML 307
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 2860-2923 9.33e-04

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: 44.28  E-value: 9.33e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 157818713 2860 YTRSVATSSIVGYILGLGDRHVQNILINEqSAELVHIDLG--VAFEQGKILPTPETVPFRLSRDIV 2923
Cdd:cd05175   203 FTRSCAGYCVATFILGIGDRHNSNIMVKD-DGQLFHIDFGhfLDHKKKKFGYKRERVPFVLTQDFL 267
 
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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