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Conserved domains on  [gi|578822207|ref|XP_006718906|]
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serine-protein kinase ATM isoform X1 [Homo sapiens]

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 ...
 2683-2962 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: 584.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2683 IQSFKAEFRLAGGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2762
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2763 RSGVLEWCTGTVPIGEFLVNN--EDGAHKRYRPNDFSAFQCQKKMMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCMEKFL 2840
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVGAssKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2841 DPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLTRDIVDGMGI 2920
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 578822207 2921 TGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWTM 2962
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2097-2489 2.04e-56

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


:

Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 200.66  E-value: 2.04e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2097 ELHYQAAWRNMQWDHCTSVSKEVEGTSYHESLYNALQSLRDREFSTFYESLKYARVKEVEEMCKRSLESVYSLYPTLSRL 2176
Cdd:pfam02259    2 PLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVRL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2177 QAIGELESIGELFSRSV-THRQLSEVYIKWQKHSQLLKDsDFSFQEPIMALRTVILEILMEKEMDnsqrecikDILTKHL 2255
Cdd:pfam02259   82 QQLAELEEIIQYKQKLGqSSEELKSLLQTWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYLG--------GYHAEMW 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2256 VELSILARTFKNTQLPERAIFQIKQYNSVSCGVsEWQLEEAQVFWAKKEQSLALSILKQMIKKldasCAANNPSLKLTYT 2335
Cdd:pfam02259  153 LKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSC----YLQKNGELLSGLE 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2336 EClrvcgnwLAETCLENPAVIMQTYLEKAVEVAGNYDGESSdELRNGKMKAFLSLARFSDTQYQrIENYMKSSEFENKQA 2415
Cdd:pfam02259  228 VI-------NPTNLEEFTELLARCYLLKGKWQAALGQNWAE-EKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVLRK 298

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578822207  2416 LLKRAKEEVgllrehkiqtnrytvkvqreleldelalralKEDRKRFLCKAVENYINCLLSGEEHDM-WVFRLCS 2489
Cdd:pfam02259  299 EEQGKEEEG-------------------------------PEDLSRYVVPAVEGYLRSLSLSSENSLqDTLRLLT 342
TAN pfam11640
Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, ...
 8-165 5.56e-19

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: 86.22  E-value: 5.56e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207     8 LLICCRQLEHDRATERKKEVEKFKRLIRDPetikhldRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSN-------RNKSLSALNDKAWHSIFEALFRLIEAEKSAYLKAKKSSTSKSA 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207    88 AsrQKKMQEISSLVKYFIKCANRrapRLKcQELLNYIMDTVKDS---SNGAI---YGADCSNIlLKDILSVRKYWCEISQ 161
Cdd:pfam11640   74 A--ARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLlplPDGELlepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 578822207   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 ...
 3026-3055 2.77e-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: 57.39  E-value: 2.77e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 578822207  3026 LSVGGQVNLLIQQAIDPKNLSRLFPGWKAW 3055
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 ...
 2683-2962 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: 584.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2683 IQSFKAEFRLAGGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2762
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2763 RSGVLEWCTGTVPIGEFLVNN--EDGAHKRYRPNDFSAFQCQKKMMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCMEKFL 2840
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVGAssKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2841 DPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLTRDIVDGMGI 2920
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 578822207 2921 TGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWTM 2962
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2715-2964 3.95e-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: 267.63  E-value: 3.95e-81
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207   2715 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEFLVNNEDGAHKRYRPn 2794
Cdd:smart00146    2 IFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL- 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207   2795 dfsafqcqkkmMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCMEKFLDPA-IWFEKRLAYTRSVATSSIVGYILGLGDRHV 2873
Cdd:smart00146   81 -----------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPSeDYFEARKNFTRSCAGYSVITYILGLGDRHN 149

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207   2874 QNILINEqSAELVHIDLGVAFEQGKILPTP-ETVPFRLTRDIVDGMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVL 2952
Cdd:smart00146  150 DNIMLDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELM 228

                           250
                    ....*....|..
gi 578822207   2953 LYDPLFDWTMNP 2964
Cdd:smart00146  229 LYDGLPDWRSGK 240
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2679-3055 3.60e-73

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 273.97  E-value: 3.60e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2679 NLVTIQSFKAEFRLA-GGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKV 2757
Cdd:COG5032  1763 PFVLIERFEPEVSVVkSHLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKV 1842

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2758 VPLSQRSGVLEWCTGTVPIGEFLvnneDGAHKRYRpndFSAFQCQKKMMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCME 2837
Cdd:COG5032  1843 IPLSPGSGIIEWVPNSDTLHSIL----REYHKRKN---ISIDQEKKLAARLDNLKLLLKDEFFTKATLKSPPVLYDWFSE 1915

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2838 KFLDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLG-VAFEQGKILPTPETVPFRLTRDIVD 2916
Cdd:COG5032  1916 SFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGfILFNAPGRFPFPEKVPFRLTRNIVE 1995

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2917 GMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWTMNPlkalylqqrpedetelhptlnaddqeckrnls 2996
Cdd:COG5032  1996 AMGVSGVEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLP-------------------------------- 2043

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578822207 2997 DIDQSFNKVAERVLMRLQEKLKG--VEEGTVLSVGGQVNLLIQQAIDPKNLSRLFPGWKAW 3055
Cdd:COG5032  2044 CFREIQNNEIVNVLERFRLKLSEkdAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPF 2104
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 2715-2962 6.05e-58

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: 201.40  E-value: 6.05e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2715 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRkltICTYKVVPLSQRSGVLEWCTGTVPIGEFLVNNEDgahKRYRPN 2794
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGE---NGVPPT 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2795 DFSAFQCQKKMMEVQKKSFEEKYEVFMDVcqnfqPVFRYFcMEKFLDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQ 2874
Cdd:pfam00454   79 AMVKILHSALNYPKLKLEFESRISLPPKV-----GLLQWF-VKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLD 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2875 NILINEQSAELVHIDLGVAF-EQGKILPTPETVPFRLTRDIVDGMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLL 2953
Cdd:pfam00454  153 NILVDKTTGKLFHIDFGLCLpDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMV 232


                   ....*....
gi 578822207  2954 YDPLFDWTM 2962
Cdd:pfam00454  233 ADGLPDWSI 241
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2097-2489 2.04e-56

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


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 200.66  E-value: 2.04e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2097 ELHYQAAWRNMQWDHCTSVSKEVEGTSYHESLYNALQSLRDREFSTFYESLKYARVKEVEEMCKRSLESVYSLYPTLSRL 2176
Cdd:pfam02259    2 PLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVRL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2177 QAIGELESIGELFSRSV-THRQLSEVYIKWQKHSQLLKDsDFSFQEPIMALRTVILEILMEKEMDnsqrecikDILTKHL 2255
Cdd:pfam02259   82 QQLAELEEIIQYKQKLGqSSEELKSLLQTWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYLG--------GYHAEMW 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2256 VELSILARTFKNTQLPERAIFQIKQYNSVSCGVsEWQLEEAQVFWAKKEQSLALSILKQMIKKldasCAANNPSLKLTYT 2335
Cdd:pfam02259  153 LKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSC----YLQKNGELLSGLE 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2336 EClrvcgnwLAETCLENPAVIMQTYLEKAVEVAGNYDGESSdELRNGKMKAFLSLARFSDTQYQrIENYMKSSEFENKQA 2415
Cdd:pfam02259  228 VI-------NPTNLEEFTELLARCYLLKGKWQAALGQNWAE-EKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVLRK 298

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578822207  2416 LLKRAKEEVgllrehkiqtnrytvkvqreleldelalralKEDRKRFLCKAVENYINCLLSGEEHDM-WVFRLCS 2489
Cdd:pfam02259  299 EEQGKEEEG-------------------------------PEDLSRYVVPAVEGYLRSLSLSSENSLqDTLRLLT 342
TAN pfam11640
Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, ...
 8-165 5.56e-19

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: 86.22  E-value: 5.56e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207     8 LLICCRQLEHDRATERKKEVEKFKRLIRDPetikhldRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSN-------RNKSLSALNDKAWHSIFEALFRLIEAEKSAYLKAKKSSTSKSA 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207    88 AsrQKKMQEISSLVKYFIKCANRrapRLKcQELLNYIMDTVKDS---SNGAI---YGADCSNIlLKDILSVRKYWCEISQ 161
Cdd:pfam11640   74 A--ARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLlplPDGELlepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 578822207   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 ...
 3026-3055 2.77e-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: 57.39  E-value: 2.77e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 578822207  3026 LSVGGQVNLLIQQAIDPKNLSRLFPGWKAW 3055
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 ...
 2683-2962 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: 584.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2683 IQSFKAEFRLAGGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2762
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2763 RSGVLEWCTGTVPIGEFLVNN--EDGAHKRYRPNDFSAFQCQKKMMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCMEKFL 2840
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVGAssKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2841 DPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLTRDIVDGMGI 2920
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 578822207 2921 TGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWTM 2962
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 2683-2955 1.92e-96

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: 311.13  E-value: 1.92e-96
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2683 IQSFKAEFRLAGGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2762
Cdd:cd05164     1 IASFDPRVRILASLQKPKKITILGSDGKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKETRKRNLTIRTYSVVPLSS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2763 RSGVLEWCTGTVPIGeflvnnedgahkryrpndfsafqcqkkmmevqkksfeekyevfmdvcqnfqPVFRYFCMEKFLDP 2842
Cdd:cd05164    81 QSGLIEWVDNTTTLK---------------------------------------------------PVLKKWFNETFPDP 109

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2843 AIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLTRDIVDGMGITG 2922
Cdd:cd05164   110 TQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIDTKTGEVVHIDFGMIFNKGKTLPVPEIVPFRLTRNIINGMGPTG 189

                         250       260       270
                  ....*....|....*....|....*....|...
gi 578822207 2923 VEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYD 2955
Cdd:cd05164   190 VEGLFRKSCEQVLRVFRKHKDKLITFLDTFLYD 222
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 2699-2961 3.26e-85

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: 279.39  E-value: 3.26e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2699 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGE 2778
Cdd:cd00892    17 PKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNLHIRTYAVIPLNEECGIIEWVPNTVTLRS 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2779 FLVnnedgahkRYRPndfsafqcqkkmmevqkksfeekyevfmdvcqnfqPVFRYFCMEKFLDPAIWFEKRLAYTRSVAT 2858
Cdd:cd00892    97 ILS--------TLYP-----------------------------------PVLHEWFLKNFPDPTAWYEARNNYTRSTAV 133

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2859 SSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLTRDIVDGMGITGVEGVFRRCCEKTMEVM 2938
Cdd:cd00892   134 MSMVGYILGLGDRHGENILFDSTTGDVVHVDFDCLFDKGLTLEVPERVPFRLTQNMVDAMGVTGVEGTFRRTCEVTLRVL 213

                         250       260
                  ....*....|....*....|...
gi 578822207 2939 RNSQETLLTIVEVLLYDPLFDWT 2961
Cdd:cd00892   214 RENRETLMSVLETFVHDPLVEWS 236
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2715-2964 3.95e-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: 267.63  E-value: 3.95e-81
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207   2715 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEFLVNNEDGAHKRYRPn 2794
Cdd:smart00146    2 IFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL- 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207   2795 dfsafqcqkkmMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCMEKFLDPA-IWFEKRLAYTRSVATSSIVGYILGLGDRHV 2873
Cdd:smart00146   81 -----------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPSeDYFEARKNFTRSCAGYSVITYILGLGDRHN 149

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207   2874 QNILINEqSAELVHIDLGVAFEQGKILPTP-ETVPFRLTRDIVDGMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVL 2952
Cdd:smart00146  150 DNIMLDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELM 228

                           250
                    ....*....|..
gi 578822207   2953 LYDPLFDWTMNP 2964
Cdd:smart00146  229 LYDGLPDWRSGK 240
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 2683-2960 1.57e-73

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: 247.78  E-value: 1.57e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2683 IQSFKAEFRLAGGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDA-VMQqVFQMCNTLLQRNTETRKRKLTICTYKVVPLS 2761
Cdd:cd05169     1 ISSFDPTLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDErVMQ-LFGLVNTLLKNDSETSRRNLSIQRYSVIPLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2762 QRSGVLEWctgtvpigeflVNNEDGAH---KRYRPNDFSAFQCQKKMMEVQKKSFE-----EKYEVFMDVCQNFQP--VF 2831
Cdd:cd05169    80 PNSGLIGW-----------VPGCDTLHsliRDYREKRKIPLNIEHRLMLQMAPDYDnltliQKVEVFEYALENTPGddLR 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2832 RYFCMeKFLDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPT-PETVPFRL 2910
Cdd:cd05169   149 RVLWL-KSPSSEAWLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLTGKVIHIDFGDCFEVAMHREKfPEKVPFRL 227

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 578822207 2911 TRDIVDGMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDW 2960
Cdd:cd05169   228 TRMLVNAMEVSGVEGTFRSTCEDVMRVLRENKDSLMAVLEAFVHDPLISW 277
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2679-3055 3.60e-73

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 273.97  E-value: 3.60e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2679 NLVTIQSFKAEFRLA-GGVNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKV 2757
Cdd:COG5032  1763 PFVLIERFEPEVSVVkSHLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKV 1842

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2758 VPLSQRSGVLEWCTGTVPIGEFLvnneDGAHKRYRpndFSAFQCQKKMMEVQKKSFEEKYEVFMDVCQNFQPVFRYFCME 2837
Cdd:COG5032  1843 IPLSPGSGIIEWVPNSDTLHSIL----REYHKRKN---ISIDQEKKLAARLDNLKLLLKDEFFTKATLKSPPVLYDWFSE 1915

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2838 KFLDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLG-VAFEQGKILPTPETVPFRLTRDIVD 2916
Cdd:COG5032  1916 SFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGfILFNAPGRFPFPEKVPFRLTRNIVE 1995

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2917 GMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWTMNPlkalylqqrpedetelhptlnaddqeckrnls 2996
Cdd:COG5032  1996 AMGVSGVEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLP-------------------------------- 2043

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578822207 2997 DIDQSFNKVAERVLMRLQEKLKG--VEEGTVLSVGGQVNLLIQQAIDPKNLSRLFPGWKAW 3055
Cdd:COG5032  2044 CFREIQNNEIVNVLERFRLKLSEkdAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPF 2104
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 2699-2961 7.78e-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: 7.78e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2699 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIge 2778
Cdd:cd05170    17 PKKLVFLGSDGKRYPYLFKGLEDLHLDERIMQFLSIVNAMLASDNEHRRRRYRARHYSVTPLGPRSGLIQWVDGATPL-- 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2779 FLV--------------NNEDGA-------------HKRYRP----NDFSAFQCQKKM-MEVQKKSFEE-KYEVFMDVCQ 2825
Cdd:cd05170    95 FSLykrwqqrraaaqaqKNQDSGstpppvprpselfYNKLKPalkaAGIRKSTSRREWpLEVLRQVLEElVAETPRDLLA 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2826 NfqpvfRYFCMEkfLDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPET 2905
Cdd:cd05170   175 R-----ELWCSS--PSSAEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDLSTGEVVHIDYNVCFEKGKRLRVPEK 247

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 578822207 2906 VPFRLTRDIVDGMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWT 2961
Cdd:cd05170   248 VPFRLTQNIEHALGPTGVEGTFRLSCEQVLKILRKGRETLLTLLEAFVYDPLVDWT 303
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 2699-2960 3.62e-61

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: 210.51  E-value: 3.62e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2699 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGE 2778
Cdd:cd05172    17 PKRITIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDPACRQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2779 FLVNNedgahkryrpndfsafqcqkkmmevqkksfeekyevfmdvcqnfqpVFRYFCMEKFLDPAIWFEKRLAYTRSVAT 2858
Cdd:cd05172    97 ILEND----------------------------------------------LLRRALLSLASSPEAFLALRSNFARSLAA 130

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2859 SSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQG-KILPTPETVPFRLTRDIVDGMGITGVEGVFRRCCEKTMEV 2937
Cdd:cd05172   131 MSICGYILGIGDRHLSNFLVDLSTGRLIGIDFGHAFGSAtQFLPIPELVPFRLTRQLLNLLQPLDARGLLRSDMVHVLRA 210

                         250       260
                  ....*....|....*....|...
gi 578822207 2938 MRNSQETLLTIVEVLLYDPLFDW 2960
Cdd:cd05172   211 LRAGRDLLLATMDVFVKEPLLDW 233
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 2715-2962 6.05e-58

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: 201.40  E-value: 6.05e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2715 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRkltICTYKVVPLSQRSGVLEWCTGTVPIGEFLVNNEDgahKRYRPN 2794
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGE---NGVPPT 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2795 DFSAFQCQKKMMEVQKKSFEEKYEVFMDVcqnfqPVFRYFcMEKFLDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHVQ 2874
Cdd:pfam00454   79 AMVKILHSALNYPKLKLEFESRISLPPKV-----GLLQWF-VKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLD 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2875 NILINEQSAELVHIDLGVAF-EQGKILPTPETVPFRLTRDIVDGMGITGVEGVFRRCCEKTMEVMRNSQETLLTIVEVLL 2953
Cdd:pfam00454  153 NILVDKTTGKLFHIDFGLCLpDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMV 232


                   ....*....
gi 578822207  2954 YDPLFDWTM 2962
Cdd:pfam00454  233 ADGLPDWSI 241
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2097-2489 2.04e-56

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


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 200.66  E-value: 2.04e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2097 ELHYQAAWRNMQWDHCTSVSKEVEGTSYHESLYNALQSLRDREFSTFYESLKYARVKEVEEMCKRSLESVYSLYPTLSRL 2176
Cdd:pfam02259    2 PLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVRL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2177 QAIGELESIGELFSRSV-THRQLSEVYIKWQKHSQLLKDsDFSFQEPIMALRTVILEILMEKEMDnsqrecikDILTKHL 2255
Cdd:pfam02259   82 QQLAELEEIIQYKQKLGqSSEELKSLLQTWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYLG--------GYHAEMW 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2256 VELSILARTFKNTQLPERAIFQIKQYNSVSCGVsEWQLEEAQVFWAKKEQSLALSILKQMIKKldasCAANNPSLKLTYT 2335
Cdd:pfam02259  153 LKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSC----YLQKNGELLSGLE 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207  2336 EClrvcgnwLAETCLENPAVIMQTYLEKAVEVAGNYDGESSdELRNGKMKAFLSLARFSDTQYQrIENYMKSSEFENKQA 2415
Cdd:pfam02259  228 VI-------NPTNLEEFTELLARCYLLKGKWQAALGQNWAE-EKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVLRK 298

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578822207  2416 LLKRAKEEVgllrehkiqtnrytvkvqreleldelalralKEDRKRFLCKAVENYINCLLSGEEHDM-WVFRLCS 2489
Cdd:pfam02259  299 EEQGKEEEG-------------------------------PEDLSRYVVPAVEGYLRSLSLSSENSLqDTLRLLT 342
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 2699-2955 2.15e-35

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: 135.54  E-value: 2.15e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2699 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLqrntETRKRKLTICTYKVVPLSQRSGVLEWctgtVPIGE 2778
Cdd:cd00142    17 PKKITLIGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSIL----EKESVNLVLPPYKVIPLSENSGLIEI----VKDAQ 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2779 FLvnnedgahkryrpndfsafqcqkkmmEVQKKSFEEK---YEVFMDVCQNFqpvfryfcmekfldpaiwfekrlayTRS 2855
Cdd:cd00142    89 TI--------------------------EDLLKSLWRKspsSQSWLNRRENF-------------------------SCS 117

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2856 VATSSIVGYILGLGDRHVQNILINEqSAELVHIDLGVAFEQGKILPTPETVPFRLTRDIVDGMGITGVEGVFRRCCEKTM 2935
Cdd:cd00142   118 LAGYSVLGYIFGIGDRHPSNIMIEP-SGNIFHIDFGFIFSGRKLAEGVETVPFRLTPMLENAMGTAGVNGPFQISMVKIM 196

                         250       260
                  ....*....|....*....|
gi 578822207 2936 EVMRNSQETLLTIVEVLLYD 2955
Cdd:cd00142   197 EILREHADLIVPILEHSLRD 216
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2699-2932 3.75e-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: 100.68  E-value: 3.75e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2699 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNtetrKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGE 2778
Cdd:cd00896    80 PLKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKE----NLDLKLTPYKVLATSPNDGLVEFVPNSKALAD 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2779 FLvnnedgahKRYrpNDFSAFqcqkkmMEVQKKSFEEKYEVFMDVCQNfqpvfryfcmekfldpaiwfekrlaYTRSVAT 2858
Cdd:cd00896   156 IL--------KKY--GSILNF------LRKHNPDESGPYGIKPEVMDN-------------------------FVKSCAG 194

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2859 SSIVGYILGLGDRHVQNILINEqSAELVHIDLGvaFeqgkIL---PTPETVPFRLTRDIVDGMGITGVEG--VFRR-CCE 2932
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 5.56e-19

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: 86.22  E-value: 5.56e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207     8 LLICCRQLEHDRATERKKEVEKFKRLIRDPetikhldRHSDSKQGKYLNWDAVFRFLQKYIQKETECLRIAKPNVSASTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSN-------RNKSLSALNDKAWHSIFEALFRLIEAEKSAYLKAKKSSTSKSA 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207    88 AsrQKKMQEISSLVKYFIKCANRrapRLKcQELLNYIMDTVKDS---SNGAI---YGADCSNIlLKDILSVRKYWCEISQ 161
Cdd:pfam11640   74 A--ARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLlplPDGELlepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 578822207   162 QQWL 165
Cdd:pfam11640  147 EDWI 150
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 2706-2927 1.93e-15

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: 78.72  E-value: 1.93e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2706 GSDGKERRQLVK---GRDDLRQDAVMQQvFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEFLvn 2782
Cdd:cd05163    25 GHDGSKYPFLVQtpsARHSRREERVMQL-FRLLNRVLERKKETRRRNLQFHVPIVVPLSPQVRLVEDDPSYISLQDIY-- 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2783 nedgahkryrpndfsafqcqkkmmevqkksfeEKYEVFMDVCQNFQP---VFRYFcMEKFLDP-AIW-FEKRLayTRSVA 2857
Cdd:cd05163   102 --------------------------------EKLEILNEIQSKMVPetiLSNYF-LRTMPSPsDLWlFRKQF--TLQLA 146

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578822207 2858 TSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKIL-PTPETVPFRLTRDIVDGMGITGVEGVF 2927
Cdd:cd05163   147 LSSFMTYVLSLGNRTPHRILISRSTGNVFMTDFLPSINSQGPLlDNNEPVPFRLTPNIQHFIGPIGVEGLL 217
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 2716-3003 2.92e-15

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: 79.06  E-value: 2.92e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2716 VKGRDDLRQDAVMQQVFQmcntLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIgeflvnneDGAHKRYrPND 2795
Cdd:cd05168    35 VKSGDDLRQELLAMQLIK----QFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSI--------DSLKKRF-PNF 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2796 FSAFQCqkkmmevqkksFEEKY-----EVFMDVCQNFqpvfryfcmekfldpaiwfekrlayTRSVATSSIVGYILGLGD 2870
Cdd:cd05168   102 TSLLDY-----------FERTFgdpnsERFKEAQRNF-------------------------VESLAAYSLVCYLLQIKD 145

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2871 RHVQNILINEQsAELVHIDLG---------VAFeqgkilptpETVPFRLTRDIVDGMGitGVEG----VFRRCCEKTMEV 2937
Cdd:cd05168   146 RHNGNILLDSE-GHIIHIDFGfmlsnspggLGF---------ETAPFKLTQEYVEVMG--GLESdmfrYFKTLMIQGFLA 213

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578822207 2938 MRNSQETLLTIVEVLLYD----PLFDWTMNPLKAlyLQQRpedeteLHPTLNadDQECKRN-LSDIDQSFN 3003
Cdd:cd05168   214 LRKHADRIVLLVEIMQQGsklpCFFGGGEFTIEQ--LRER------FKLNLT--EEECAQFvDSLIDKSLN 274
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 2716-3003 4.48e-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: 4.48e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2716 VKGRDDLRQDA-------VMQQVFQMCNTllqrntetrkrKLTICTYKVVPLSQRSGVLEWCtgtvpigeflvnnedgah 2788
Cdd:cd00893    32 VKTGDDLKQEQlalqlisQFDQIFKEEGL-----------PLWLRPYEILSLGPDSGIIEMI------------------ 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2789 kryrPNDFSAFQCQKKMMEVQKKS-----FEEKYEVfmdvcQNFQPVFRYFCmekfldpaiwfekrlaytRSVATSSIVG 2863
Cdd:cd00893    83 ----KNAVSIDSLKKKLDSFNKFVslsdfFDDNFGD-----EAIQKARDNFL------------------QSLVAYSLVC 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2864 YILGLGDRHVQNILINEQsAELVHIDLGVAFEQgkilpTP-----ETVPFRLTRDIVDGMGITGVE--GVFRRCCEKTME 2936
Cdd:cd00893   136 YFLQIKDRHNGNILLDKE-GHIIHIDFGFFLSS-----HPgfygfEGAPFKLSSEYIEVLGGVDSElfKEFRKLFLKGFM 209

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578822207 2937 VMRNSQETLLTIVEvLLYDPLFDWTMNPLKALYLQQRpedeteLHPTLNadDQECKRNLSD-IDQSFN 3003
Cdd:cd00893   210 ALRKHSDKILSLVE-MMYSGHGITCFGKKTIQQLKQR------FNPELT--EGELEVYVLSlINKSLD 268
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 2686-2954 1.43e-11

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: 68.39  E-value: 1.43e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2686 FKAEFRLA-GGVNLPKIIDCVGSDGKERRQ--LVKGRDDLRQD-------AVMQQVFQMCNTllqrntetrkrKLTICTY 2755
Cdd:cd05167    21 FLVTFKVKdCGVDELEHEGTESEATKEVWQaaIFKVGDDCRQDmlalqliSLFKNIFEEVGL-----------DLYLFPY 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2756 KVVPLSQRSGVLEwctgtvpigefLVNNEDGAHKRYRPNDFSAFQcqkkmmevqkkSFEEKYEVFMDVcqNFQpvfryfc 2835
Cdd:cd05167    90 RVVATGPGCGVIE-----------VIPNSKSRDQIGRETDNGLYE-----------YFLSKYGDESTP--AFQ------- 138

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2836 mekfldpaiwfEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQsAELVHIDLGVAFEQ--GKILPTpETVPFRLTRD 2913
Cdd:cd05167   139 -----------KARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDD-GHIIHIDFGFIFEIspGGNLGF-ESAPFKLTKE 205

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 578822207 2914 IVDGMGITGVEGVFRRCCEKTMEVM---RNSQETLLTIVEVLLY 2954
Cdd:cd05167   206 MVDLMGGSMESEPFKWFVELCVRGYlavRPYAEAIVSLVELMLD 249
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 2686-2939 1.46e-10

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: 65.84  E-value: 1.46e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2686 FKAEFRLAGGVNLpkiidcvgsdgkerrqLVKGRDDLRQDAVMQQVFQMCNTLLQrnteTRKRKLTICTYKVVPLSQRSG 2765
Cdd:cd05174    88 YSSEEAGAGNVGI----------------IFKNGDDLRQDMLTLQMIQLMDVLWK----QEGLDLRMTPYGCLSTGDKTG 147

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2766 VLEWCTGTVPIGEFLVNNEDGAHKryrpndfSAFQCQKKMMEVQKKSFEEKyevfmdvcqnfqpvfryfcmekfLDPAIw 2845
Cdd:cd05174   148 LIEVVLHSDTIANIQLNKSNMAAT-------AAFNKDALLNWLKSKNPGDA-----------------------LDQAI- 196

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2846 fEKrlaYTRSVATSSIVGYILGLGDRHVQNILINEqSAELVHIDLG--VAFEQGKILPTPETVPFRLTRDIVDGM--GIT 2921
Cdd:cd05174   197 -EE---FTLSCAGYCVATYVLGIGDRHSDNIMIRE-SGQLFHIDFGhfLGNFKTKFGINRERVPFILTYDFVHVIqqGKT 271

                         250       260
                  ....*....|....*....|.
gi 578822207 2922 GVEGVFRR---CCEKTMEVMR 2939
Cdd:cd05174   272 NNSEKFERfrgYCERAYTILR 292
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 3026-3055 2.77e-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: 57.39  E-value: 2.77e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 578822207  3026 LSVGGQVNLLIQQAIDPKNLSRLFPGWKAW 3055
Cdd:pfam02260    2 LSVEGQVDELIQEATDPENLAQMYIGWCPW 31
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 2715-2953 4.57e-09

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: 61.13  E-value: 4.57e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2715 LVKGRDDLRQDAVMQQVFQMCNTLLQRntetRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEFLVNNEDGAHKryrpn 2794
Cdd:cd05173    98 IFKNGDDLRQDMLTLQILRLMDTLWKE----AGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQLNSSNVAAA----- 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2795 dfSAFQcqkkmmevqkksfeekyevfMDVCQNFqpvFRYFCMEKFLDPAIWfekrlAYTRSVATSSIVGYILGLGDRHVQ 2874
Cdd:cd05173   169 --AAFN--------------------KDALLNW---LKEYNSGDDLERAIE-----EFTLSCAGYCVATYVLGIGDRHSD 218

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2875 NILInEQSAELVHIDLG--VAFEQGKILPTPETVPFRLTRDIVDGM--GITGVE---GVFRRCCEKTMEVMRNSQETLLT 2947
Cdd:cd05173   219 NIMV-RKNGQLFHIDFGhiLGNFKSKFGIKRERVPFILTYDFIHVIqqGKTGNTekfGRFRQYCEDAYLILRKNGNLFIT 297


                  ....*.
gi 578822207 2948 IVEVLL 2953
Cdd:cd05173   298 LFALML 303
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2720-2976 7.48e-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: 54.22  E-value: 7.48e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2720 DDLRQDA-VMQQVFQMCNTLLQRNTEtrkrkLTICTYKVVPLSQRSGVLEwctgtvpigefLVNNedgahkryrpndfsa 2798
Cdd:cd05166    99 DDLRQDMlTLQLIRIMDKIWLQEGLD-----LKMITFRCVPTGNKRGMVE-----------LVPE--------------- 147

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2799 fqcQKKMMEVQKK-----SFEEKyeVFMDVCQNFQPvfryfcmekflDPAIWFEKRLAYTRSVATSSIVGYILGLGDRHV 2873
Cdd:cd05166   148 ---AETLREIQTEhgltgSFKDR--PLADWLQKHNP-----------SELEYEKAVENFIRSCAGYCVATYVLGICDRHN 211

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2874 QNILInEQSAELVHIDLgvafeqGKILPTPET--------VPFRLTRD----IVDGMGITGVEGVFRRCCEKTMEVMRNS 2941
Cdd:cd05166   212 DNIML-KTSGHLFHIDF------GKFLGDAQMfgnfkrdrVPFVLTSDmayvINGGDKPSSRFQLFVDLCCQAFNIIRKN 284

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 578822207 2942 QETLLTIVEVLLYDPLFDWTMNPLKALYLQQRPED 2976
Cdd:cd05166   285 SNLLLNLLSLMLSSGIPGVTQDDLRYVQDALLPEL 319
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2852-2939 3.00e-06

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: 52.25  E-value: 3.00e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2852 YTRSVATSSIVGYILGLGDRHVQNILINEqSAELVHIDLgvafeqGKILP--------TPETVPFRLTRD----IVDGMG 2919
Cdd:cd05165   197 FTLSCAGYCVATYVLGIGDRHSDNIMVKE-NGQLFHIDF------GHFLGnfkkkfgiKRERVPFVLTHDfvyvIARGQD 269

                          90       100
                  ....*....|....*....|..
gi 578822207 2920 ITGVEGV--FRRCCEKTMEVMR 2939
Cdd:cd05165   270 NTKSEEFqeFQELCEKAYLILR 291
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2720-2948 4.01e-06

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: 51.80  E-value: 4.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2720 DDLRQDAVMQQVFQMCNTLLQRntETRKRKLTIctYKVVPLSQRSGVLEWCTGTVPIGEFlvnnedgaHKRYRPNdFSAF 2799
Cdd:cd00891    96 DDLRQDQLTLQLLRIMDKLWKK--EGLDLRMTP--YKCIATGDEVGMIEVVPNSETTAAI--------QKKYGGF-GAAF 162

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2800 QcQKKMME--VQKKSFEEKYEVFMDvcqNFqpvfryfcmekfldpaiwfekrlayTRS-----VATssivgYILGLGDRH 2872
Cdd:cd00891   163 K-DTPISNwlKKHNPTEEEYEEAVE---NF-------------------------IRScagycVAT-----YVLGIGDRH 208

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2873 VQNILINeQSAELVHIDlgvaFeqGKIL---PTP-----ETVPFRLTRDIVDGMGitGVEGV----FRRCCEKTMEVMRN 2940
Cdd:cd00891   209 NDNIMVT-KSGHLFHID----F--GHFLgnfKKKfgikrERAPFVFTPEMAYVMG--GEDSEnfqkFEDLCCKAYNILRK 279


                  ....*...
gi 578822207 2941 SQETLLTI 2948
Cdd:cd00891   280 HGNLLINL 287
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 2852-2981 1.55e-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: 50.25  E-value: 1.55e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2852 YTRSVATSSIVGYILGLGDRHVQNILINEQsAELVHIDLGVAFEQGKIL--PTPETVPFRLTRDIVDGMGITGVEGV--- 2926
Cdd:cd00894   200 FVYSCAGYCVATFVLGIGDRHNDNIMITET-GNLFHIDFGHILGNYKSFlgINKERVPFVLTPDFLFVMGTSGKKTSlhf 278

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578822207 2927 --FRRCCEKTMEVMRNSQETLLTIVEVLLYDPLFDWTMNP----LKALYLQQRPEDETELH 2981
Cdd:cd00894   279 qkFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEdieyIRDALTVGKSEEDAKKH 339
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 2852-2915 4.45e-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: 45.43  E-value: 4.45e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578822207 2852 YTRSVATSSIVGYILGLGDRHVQNILINEqSAELVHIDLG--VAFEQGKILPTPETVPFRLTRDIV 2915
Cdd:cd05175   203 FTRSCAGYCVATFILGIGDRHNSNIMVKD-DGQLFHIDFGhfLDHKKKKFGYKRERVPFVLTQDFL 267
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 2704-2983 5.69e-03

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: 41.80  E-value: 5.69e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2704 CVGSDGKERRQLVKGRDDLRQDAVMQQVFQ-MCNTLLQRNTEtrkrkLTICTYKVVPLSQRSGVLEWCTGTVPIGEflVN 2782
Cdd:cd05177    84 NANPLAKNISIIFKTGDDLRQDMLVLQIVRvMDNIWLQEGLD-----MQMIIYRCLSTGKTQGLVQMVPDAVTLAK--IH 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2783 NEDGAHKRYRPNDFSA-FQCQKKMmevqKKSFEEKYEVFMDVCqnfqpvfryfcmekfldpAIWfekrlaytrsvatsSI 2861
Cdd:cd05177   157 RESGLIGPLKENTIEKwFHMHNKL----KEDYDKAVRNFFHSC------------------AGW--------------CV 200

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822207 2862 VGYILGLGDRHVQNILINeQSAELVHIDLgvafeqGKILPTPET--------VPFRLTRDIV-----DGMGITGVEGVFR 2928
Cdd:cd05177   201 VTFILGVCDRHNDNIMLT-HSGHMFHIDF------GKFLGHAQTfgsikrdrAPFIFTSEMEyfiteGGKKPQRFQRFVE 273

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 578822207 2929 RCCEkTMEVMRNSQETLLTIVEVLLYDPLFDWT-MNPLKALYLQQRPEDeTELHPT 2983
Cdd:cd05177   274 LCCR-AYNIVRKHSQLLLNLLEMMLHAGLPELKdIQDLKYVYNNLRPQD-TDLEAT 327
 
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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