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Conserved domains on  [gi|755528316|ref|XP_011240687|]
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serine-protein kinase ATM isoform X1 [Mus musculus]

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 ...
 2704-2983 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 755528316 2704 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2783
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2784 RSGVLEWCTGTVPIGEYLV--NSEDGAHRRYRPNDFSANQCQKKMMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFL 2861
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVgaSSKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2862 DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGI 2941
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 755528316 2942 TGVEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWTM 2983
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2116-2510 5.46e-66

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


:

Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 228.39  E-value: 5.46e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2116 QELRYQAAWRNMQWGLCASAGQEVEGTSYHESLYNALQCLRNREFSTFYESLRYARVKEVEELSKGSLESVYSLYPTLSR 2195
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2196 LQAIGELENSGELFSRSVTDRERSEA-YWKWQKHSQLLKDsDFSFQEPLMALRTVILETLVQKEMersqgacsKDILTKH 2274
Cdd:pfam02259   81 LQQLAELEEIIQYKQKLGQSSEELKSlLQTWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYL--------GGYHAEM 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2275 LVEFSVLARTFKNTQLPERAIFKIKQYNSAICGIsEWHLEEAQVFWAKKEQSLALSILKQMIKKLdsSFKDKENDAGLKV 2354
Cdd:pfam02259  152 WLKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSCY--LQKNGELLSGLEV 228

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2355 IyaeclrvcgswLAETCLENPAVIMQTYLEKAVKVAGSYDGNSRELRNGQMKAFLSLARFSDTQYQrIENYMKSSEFENK 2434
Cdd:pfam02259  229 I-----------NPTNLEEFTELLARCYLLKGKWQAALGQNWAEEKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVL 296

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755528316  2435 QTLLKRAKEEVgllrehkiqtnrytvkvqreleldecalralREDRKRFLCKAVENYINCLLSGEEHDL-WVFRLCS 2510
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 3.14e-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: 89.69  E-value: 3.14e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316     8 LLICCRQLEHDRATERRKEVDKFKRLIQDPETVQhlDRHSDSKQgkylnWDAVFRFLQKYIQKEMESLRTAKSnvSATTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSNRNKS--LSALNDKA-----WHSIFEALFRLIEAEKSAYLKAKK--SSTSK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316    88 SSRQKKMQEISSLVRYFIKCANKrapRLKcQDLLNYVMDTVKDSSNGLT------YGADCSNIlLKDILSVRKYWCEVSQ 161
Cdd:pfam11640   72 SAAARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLLPLPDgellepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 755528316   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 ...
 3047-3076 1.57e-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: 1.57e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 755528316  3047 LSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3076
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 ...
 2704-2983 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 755528316 2704 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2783
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2784 RSGVLEWCTGTVPIGEYLV--NSEDGAHRRYRPNDFSANQCQKKMMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFL 2861
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVgaSSKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2862 DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGI 2941
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 755528316 2942 TGVEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWTM 2983
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2736-2985 6.78e-82

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: 269.94  E-value: 6.78e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316   2736 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEYLVNSEDGAHRRYRPn 2815
Cdd:smart00146    2 IFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL- 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316   2816 dfsanqcqkkmMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFLDPA-VWFEKRLAYTRSVATSSIVGYILGLGDRHV 2894
Cdd:smart00146   81 -----------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPSeDYFEARKNFTRSCAGYSVITYILGLGDRHN 149

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316   2895 QNILINEqSAELVHIDLGVAFEQGKILPTP-ETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQETLLTIVEVL 2973
Cdd:smart00146  150 DNIMLDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELM 228

                           250
                    ....*....|..
gi 755528316   2974 LYDPLFDWTMNP 2985
Cdd:smart00146  229 LYDGLPDWRSGK 240
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2556-3076 8.63e-75

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 278.98  E-value: 8.63e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2556 LGFHEVLNNLISRISLDHPhhtlFIILALANankdeflSKPETTRRSRITKSTSKEnshldEDRTEAATRIIHSIRSK-R 2634
Cdd:COG5032  1637 LLFEPILAQLLSRLSSENN----KISVALLI-------DKPLHEERENFPSGLSLS-----SFQSSFLKELIKKSPRKiR 1700

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2635 CKMVKDMEALCDAY-IILANMdaSQWRAQRKGInipanqpITKLKNLEDVV---VPTMEIKVDPtGEYE---NLVTIKSF 2707
Cdd:COG5032  1701 KKFKIDISLLNLSRkLYISVL--RSIRKRLKRL-------LELRLKKVSPKlllFHAFLEIKLP-GQYLldkPFVLIERF 1770

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2708 KTEFRLA-GGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSG 2786
Cdd:COG5032  1771 EPEVSVVkSHLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKVIPLSPGSG 1850

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2787 VLEWCTGTVPIGEYLvnsedgahRRYRPND-FSANQCQKKMMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFLDPAV 2865
Cdd:COG5032  1851 IIEWVPNSDTLHSIL--------REYHKRKnISIDQEKKLAARLDNLKLLLKDEFFTKATLKSPPVLYDWFSESFPNPED 1922

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2866 WFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLG-VAFEQGKILPTPETVPFRLSRDIVDGMGITGV 2944
Cdd:COG5032  1923 WLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGfILFNAPGRFPFPEKVPFRLTRNIVEAMGVSGV 2002

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2945 EGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWTMNPlkalylqqrpedesdlhstpnaddqeckqslsDTDQSFN 3024
Cdd:COG5032  2003 EGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLP--------------------------------CFREIQN 2050

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....
gi 755528316 3025 KVAERVLMRLQEKLKG--VEEGTVLSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3076
Cdd:COG5032  2051 NEIVNVLERFRLKLSEkdAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPF 2104
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2116-2510 5.46e-66

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


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 228.39  E-value: 5.46e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2116 QELRYQAAWRNMQWGLCASAGQEVEGTSYHESLYNALQCLRNREFSTFYESLRYARVKEVEELSKGSLESVYSLYPTLSR 2195
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2196 LQAIGELENSGELFSRSVTDRERSEA-YWKWQKHSQLLKDsDFSFQEPLMALRTVILETLVQKEMersqgacsKDILTKH 2274
Cdd:pfam02259   81 LQQLAELEEIIQYKQKLGQSSEELKSlLQTWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYL--------GGYHAEM 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2275 LVEFSVLARTFKNTQLPERAIFKIKQYNSAICGIsEWHLEEAQVFWAKKEQSLALSILKQMIKKLdsSFKDKENDAGLKV 2354
Cdd:pfam02259  152 WLKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSCY--LQKNGELLSGLEV 228

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2355 IyaeclrvcgswLAETCLENPAVIMQTYLEKAVKVAGSYDGNSRELRNGQMKAFLSLARFSDTQYQrIENYMKSSEFENK 2434
Cdd:pfam02259  229 I-----------NPTNLEEFTELLARCYLLKGKWQAALGQNWAEEKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVL 296

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755528316  2435 QTLLKRAKEEVgllrehkiqtnrytvkvqreleldecalralREDRKRFLCKAVENYINCLLSGEEHDL-WVFRLCS 2510
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 ...
 2736-2983 2.16e-59

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: 205.64  E-value: 2.16e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2736 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRkltICTYKVVPLSQRSGVLEWctgtvpigeyLVNSEDGA--HRRYR 2813
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEW----------VPNSETLAyiLDEYG 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2814 PNDFSANQCQKKM-----MEVQKKSFEEKYDTFMTIcqnfePVFRYFcMEKFLDPAVWFEKRLAYTRSVATSSIVGYILG 2888
Cdd:pfam00454   72 ENGVPPTAMVKILhsalnYPKLKLEFESRISLPPKV-----GLLQWF-VKKSPDAEEWGEARKNFVRSCAGYSVLDYILG 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2889 LGDRHVQNILINEQSAELVHIDLGVAF-EQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQETLL 2967
Cdd:pfam00454  146 NGDRHLDNILVDKTTGKLFHIDFGLCLpDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLT 225

                          250
                   ....*....|....*.
gi 755528316  2968 TIVEVLLYDPLFDWTM 2983
Cdd:pfam00454  226 NLLKLMVADGLPDWSI 241
TAN pfam11640
Telomere-length maintenance and DNA damage repair; ATM is a large protein kinase, in humans, ...
 8-165 3.14e-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: 89.69  E-value: 3.14e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316     8 LLICCRQLEHDRATERRKEVDKFKRLIQDPETVQhlDRHSDSKQgkylnWDAVFRFLQKYIQKEMESLRTAKSnvSATTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSNRNKS--LSALNDKA-----WHSIFEALFRLIEAEKSAYLKAKK--SSTSK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316    88 SSRQKKMQEISSLVRYFIKCANKrapRLKcQDLLNYVMDTVKDSSNGLT------YGADCSNIlLKDILSVRKYWCEVSQ 161
Cdd:pfam11640   72 SAAARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLLPLPDgellepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 755528316   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 ...
 3047-3076 1.57e-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: 1.57e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 755528316  3047 LSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3076
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 ...
 2704-2983 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 755528316 2704 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2783
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKLRIRTYKVVPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2784 RSGVLEWCTGTVPIGEYLV--NSEDGAHRRYRPNDFSANQCQKKMMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFL 2861
Cdd:cd05171    81 RSGVLEFVENTIPLGEYLVgaSSKSGAHARYRPKDWTASTCRKKMREKAKASAEERLKVFDEICKNFKPVFRHFFLEKFP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2862 DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGI 2941
Cdd:cd05171   161 DPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDGMGI 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 755528316 2942 TGVEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWTM 2983
Cdd:cd05171   241 TGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 2704-2976 7.19e-97

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: 312.28  E-value: 7.19e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2704 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2783
Cdd:cd05164     1 IASFDPRVRILASLQKPKKITILGSDGKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKETRKRNLTIRTYSVVPLSS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2784 RSGVLEWCTGTVPIGeylvnsedgahrryrpndfsanqcqkkmmevqkksfeekydtfmticqnfePVFRYFCMEKFLDP 2863
Cdd:cd05164    81 QSGLIEWVDNTTTLK---------------------------------------------------PVLKKWFNETFPDP 109

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2864 AVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITG 2943
Cdd:cd05164   110 TQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIDTKTGEVVHIDFGMIFNKGKTLPVPEIVPFRLTRNIINGMGPTG 189

                         250       260       270
                  ....*....|....*....|....*....|...
gi 755528316 2944 VEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYD 2976
Cdd:cd05164   190 VEGLFRKSCEQVLRVFRKHKDKLITFLDTFLYD 222
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 2704-2982 1.23e-84

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: 277.85  E-value: 1.23e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2704 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2783
Cdd:cd00892     1 ISGFEDEVEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2784 RSGVLEWCTGTVPIGEYLvnsedgahRRYRPndfsanqcqkkmmevqkksfeekydtfmticqnfePVFRYFCMEKFLDP 2863
Cdd:cd00892    81 ECGIIEWVPNTVTLRSIL--------STLYP-----------------------------------PVLHEWFLKNFPDP 117

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2864 AVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITG 2943
Cdd:cd00892   118 TAWYEARNNYTRSTAVMSMVGYILGLGDRHGENILFDSTTGDVVHVDFDCLFDKGLTLEVPERVPFRLTQNMVDAMGVTG 197

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 755528316 2944 VEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWT 2982
Cdd:cd00892   198 VEGTFRRTCEVTLRVLRENRETLMSVLETFVHDPLVEWS 236
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2736-2985 6.78e-82

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: 269.94  E-value: 6.78e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316   2736 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEYLVNSEDGAHRRYRPn 2815
Cdd:smart00146    2 IFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL- 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316   2816 dfsanqcqkkmMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFLDPA-VWFEKRLAYTRSVATSSIVGYILGLGDRHV 2894
Cdd:smart00146   81 -----------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPSeDYFEARKNFTRSCAGYSVITYILGLGDRHN 149

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316   2895 QNILINEqSAELVHIDLGVAFEQGKILPTP-ETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQETLLTIVEVL 2973
Cdd:smart00146  150 DNIMLDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELM 228

                           250
                    ....*....|..
gi 755528316   2974 LYDPLFDWTMNP 2985
Cdd:smart00146  229 LYDGLPDWRSGK 240
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2556-3076 8.63e-75

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 278.98  E-value: 8.63e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2556 LGFHEVLNNLISRISLDHPhhtlFIILALANankdeflSKPETTRRSRITKSTSKEnshldEDRTEAATRIIHSIRSK-R 2634
Cdd:COG5032  1637 LLFEPILAQLLSRLSSENN----KISVALLI-------DKPLHEERENFPSGLSLS-----SFQSSFLKELIKKSPRKiR 1700

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2635 CKMVKDMEALCDAY-IILANMdaSQWRAQRKGInipanqpITKLKNLEDVV---VPTMEIKVDPtGEYE---NLVTIKSF 2707
Cdd:COG5032  1701 KKFKIDISLLNLSRkLYISVL--RSIRKRLKRL-------LELRLKKVSPKlllFHAFLEIKLP-GQYLldkPFVLIERF 1770

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2708 KTEFRLA-GGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSG 2786
Cdd:COG5032  1771 EPEVSVVkSHLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKVIPLSPGSG 1850

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2787 VLEWCTGTVPIGEYLvnsedgahRRYRPND-FSANQCQKKMMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFLDPAV 2865
Cdd:COG5032  1851 IIEWVPNSDTLHSIL--------REYHKRKnISIDQEKKLAARLDNLKLLLKDEFFTKATLKSPPVLYDWFSESFPNPED 1922

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2866 WFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLG-VAFEQGKILPTPETVPFRLSRDIVDGMGITGV 2944
Cdd:COG5032  1923 WLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGfILFNAPGRFPFPEKVPFRLTRNIVEAMGVSGV 2002

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2945 EGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWTMNPlkalylqqrpedesdlhstpnaddqeckqslsDTDQSFN 3024
Cdd:COG5032  2003 EGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLP--------------------------------CFREIQN 2050

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....
gi 755528316 3025 KVAERVLMRLQEKLKG--VEEGTVLSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3076
Cdd:COG5032  2051 NEIVNVLERFRLKLSEkdAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPF 2104
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 2704-2981 1.04e-71

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: 242.39  E-value: 1.04e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2704 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDA-VMQqVFQMCNTLLQRNTETRKRKLTICTYKVVPLS 2782
Cdd:cd05169     1 ISSFDPTLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDErVMQ-LFGLVNTLLKNDSETSRRNLSIQRYSVIPLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2783 QRSGVLEWCTGTvpigeylvnseDGAH---RRYRPNDFSANQCQKKMMEvqkkSFEEKYDtFMTICQNFEpVFRYFC--- 2856
Cdd:cd05169    80 PNSGLIGWVPGC-----------DTLHsliRDYREKRKIPLNIEHRLML----QMAPDYD-NLTLIQKVE-VFEYALent 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2857 ----MEKFL-----DPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPT-PET 2926
Cdd:cd05169   143 pgddLRRVLwlkspSSEAWLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLTGKVIHIDFGDCFEVAMHREKfPEK 222

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 755528316 2927 VPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDW 2981
Cdd:cd05169   223 VPFRLTRMLVNAMEVSGVEGTFRSTCEDVMRVLRENKDSLMAVLEAFVHDPLISW 277
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 2699-2982 2.03e-68

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: 234.07  E-value: 2.03e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2699 ENLVTIKSFKTEfrlagglnlPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKV 2778
Cdd:cd05170     5 GSTVTVLPTKTK---------PKKLVFLGSDGKRYPYLFKGLEDLHLDERIMQFLSIVNAMLASDNEHRRRRYRARHYSV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2779 VPLSQRSGVLEWCTGTVPI----------GEYLVNSEDGAH-----RRYRPNDFSANQCQKKM---------------ME 2828
Cdd:cd05170    76 TPLGPRSGLIQWVDGATPLfslykrwqqrRAAAQAQKNQDSgstppPVPRPSELFYNKLKPALkaagirkstsrrewpLE 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2829 VQKKSFEEkydtfmtICQNFEPVFRY---FCMEkfLDPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAE 2905
Cdd:cd05170   156 VLRQVLEE-------LVAETPRDLLArelWCSS--PSSAEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDLSTGE 226

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755528316 2906 LVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWT 2982
Cdd:cd05170   227 VVHIDYNVCFEKGKRLRVPEKVPFRLTQNIEHALGPTGVEGTFRLSCEQVLKILRKGRETLLTLLEAFVYDPLVDWT 303
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 2116-2510 5.46e-66

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


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 228.39  E-value: 5.46e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2116 QELRYQAAWRNMQWGLCASAGQEVEGTSYHESLYNALQCLRNREFSTFYESLRYARVKEVEELSKGSLESVYSLYPTLSR 2195
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLMKKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGESYNRAYPLLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2196 LQAIGELENSGELFSRSVTDRERSEA-YWKWQKHSQLLKDsDFSFQEPLMALRTVILETLVQKEMersqgacsKDILTKH 2274
Cdd:pfam02259   81 LQQLAELEEIIQYKQKLGQSSEELKSlLQTWRNRLPGCQD-DVEIWQDILTVRSLVLSPIEDVYL--------GGYHAEM 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2275 LVEFSVLARTFKNTQLPERAIFKIKQYNSAICGIsEWHLEEAQVFWAKKEQSLALSILKQMIKKLdsSFKDKENDAGLKV 2354
Cdd:pfam02259  152 WLKFANLARKSGRFSLAEKALLKLLGEDPEEWLP-EVVYAYAKYLWPTGEQQEALLKLREFLSCY--LQKNGELLSGLEV 228

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2355 IyaeclrvcgswLAETCLENPAVIMQTYLEKAVKVAGSYDGNSRELRNGQMKAFLSLARFSDTQYQrIENYMKSSEFENK 2434
Cdd:pfam02259  229 I-----------NPTNLEEFTELLARCYLLKGKWQAALGQNWAEEKSEEILQAYLLATQFDPSWYK-AWHTWALFNFEVL 296

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755528316  2435 QTLLKRAKEEVgllrehkiqtnrytvkvqreleldecalralREDRKRFLCKAVENYINCLLSGEEHDL-WVFRLCS 2510
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, ...
 2704-2981 5.23e-60

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: 207.04  E-value: 5.23e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2704 IKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQ 2783
Cdd:cd05172     1 IVGFDPRVLVLSSKRRPKRITIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDPACRQRRLRIRTYQVIPMTS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2784 RSGVLEWCTGTVPIGEYLvnsEDGAHRRyrpndfsanqcqkkmmevqkksfeekydTFMTICQNFEpvfryfcmekfldp 2863
Cdd:cd05172    81 RLGLIEWVDNTTPLKEIL---ENDLLRR----------------------------ALLSLASSPE-------------- 115

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2864 aVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQG-KILPTPETVPFRLSRDIVDGMGIT 2942
Cdd:cd05172   116 -AFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVDLSTGRLIGIDFGHAFGSAtQFLPIPELVPFRLTRQLLNLLQPL 194

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 755528316 2943 GVEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDW 2981
Cdd:cd05172   195 DARGLLRSDMVHVLRALRAGRDLLLATMDVFVKEPLLDW 233
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 2736-2983 2.16e-59

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: 205.64  E-value: 2.16e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2736 LVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRkltICTYKVVPLSQRSGVLEWctgtvpigeyLVNSEDGA--HRRYR 2813
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEW----------VPNSETLAyiLDEYG 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2814 PNDFSANQCQKKM-----MEVQKKSFEEKYDTFMTIcqnfePVFRYFcMEKFLDPAVWFEKRLAYTRSVATSSIVGYILG 2888
Cdd:pfam00454   72 ENGVPPTAMVKILhsalnYPKLKLEFESRISLPPKV-----GLLQWF-VKKSPDAEEWGEARKNFVRSCAGYSVLDYILG 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316  2889 LGDRHVQNILINEQSAELVHIDLGVAF-EQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQETLL 2967
Cdd:pfam00454  146 NGDRHLDNILVDKTTGKLFHIDFGLCLpDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLT 225

                          250
                   ....*....|....*.
gi 755528316  2968 TIVEVLLYDPLFDWTM 2983
Cdd:pfam00454  226 NLLKLMVADGLPDWSI 241
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 2720-2976 1.28e-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: 133.23  E-value: 1.28e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2720 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLqrntETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIge 2799
Cdd:cd00142    17 PKKITLIGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSIL----EKESVNLVLPPYKVIPLSENSGLIEIVKDAQTI-- 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2800 ylvnsedgahrryrpndfsanqcqkkmmEVQKKSFEEKydtfmtiCQNFEpvfryfcmekfldpaVWFEKRLAYTRSVAT 2879
Cdd:cd00142    91 ----------------------------EDLLKSLWRK-------SPSSQ---------------SWLNRRENFSCSLAG 120

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2880 SSIVGYILGLGDRHVQNILINEqSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVM 2959
Cdd:cd00142   121 YSVLGYIFGIGDRHPSNIMIEP-SGNIFHIDFGFIFSGRKLAEGVETVPFRLTPMLENAMGTAGVNGPFQISMVKIMEIL 199

                         250
                  ....*....|....*..
gi 755528316 2960 RSSQETLLTIVEVLLYD 2976
Cdd:cd00142   200 REHADLIVPILEHSLRD 216
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2720-2953 5.38e-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: 5.38e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2720 PKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRntETRKRKLTicTYKVVPLSQRSGVLEWCTGTVPIGE 2799
Cdd:cd00896    80 PLKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKK--ENLDLKLT--PYKVLATSPNDGLVEFVPNSKALAD 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2800 YLvnsedgahrryrpndfsanqcqkkmmevqkksfeEKYDTFMTICQNFEPvfryfcmEKFLDPAVWFEKRLAYTRSVAT 2879
Cdd:cd00896   156 IL----------------------------------KKYGSILNFLRKHNP-------DESGPYGIKPEVMDNFVKSCAG 194

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2880 SSIVGYILGLGDRHVQNILINEqSAELVHIDLGvaFeqgkIL---PTPETVPFRLSRDIVDGMGITGVEG--VFRR-CCE 2953
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 3.14e-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: 89.69  E-value: 3.14e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316     8 LLICCRQLEHDRATERRKEVDKFKRLIQDPETVQhlDRHSDSKQgkylnWDAVFRFLQKYIQKEMESLRTAKSnvSATTQ 87
Cdd:pfam11640    1 LLEILSLLSSSKIKERNDALEDLKHILSSNRNKS--LSALNDKA-----WHSIFEALFRLIEAEKSAYLKAKK--SSTSK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316    88 SSRQKKMQEISSLVRYFIKCANKrapRLKcQDLLNYVMDTVKDSSNGLT------YGADCSNIlLKDILSVRKYWCEVSQ 161
Cdd:pfam11640   72 SAAARRLSSAASALRLVVEKAVS---RLK-RKTLKALLDHITQLLPLPDgellepLALDYSKA-LRSLLSYRPHVEHLDA 146


                   ....
gi 755528316   162 QQWL 165
Cdd:pfam11640  147 EDWI 150
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 2727-2948 1.03e-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: 76.79  E-value: 1.03e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2727 GSDGKERRQLVK---GRDDLRQDAVMQQvFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEYLvn 2803
Cdd:cd05163    25 GHDGSKYPFLVQtpsARHSRREERVMQL-FRLLNRVLERKKETRRRNLQFHVPIVVPLSPQVRLVEDDPSYISLQDIY-- 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2804 sedgahrryrpndfsanqcqkkmmevqkksfeEKYDTFMTICQNFEP---VFRYFcMEKFLDP-AVW-FEKRLayTRSVA 2878
Cdd:cd05163   102 --------------------------------EKLEILNEIQSKMVPetiLSNYF-LRTMPSPsDLWlFRKQF--TLQLA 146

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755528316 2879 TSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKIL-PTPETVPFRLSRDIVDGMGITGVEGVF 2948
Cdd:cd05163   147 LSSFMTYVLSLGNRTPHRILISRSTGNVFMTDFLPSINSQGPLlDNNEPVPFRLTPNIQHFIGPIGVEGLL 217
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 2737-2977 3.99e-14

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: 75.60  E-value: 3.99e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2737 VKGRDDLRQDAVMQQVFQmcntLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIgeylvnseDGAHRRYRPnd 2816
Cdd:cd05168    35 VKSGDDLRQELLAMQLIK----QFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSI--------DSLKKRFPN-- 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2817 fsanqcqkkmmevqkksfeekydtFMTICQNFEPVFRYFCMEKFLdpavwfEKRLAYTRSVATSSIVGYILGLGDRHVQN 2896
Cdd:cd05168   101 ------------------------FTSLLDYFERTFGDPNSERFK------EAQRNFVESLAAYSLVCYLLQIKDRHNGN 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2897 ILINEQsAELVHIDLG---------VAFeqgkilptpETVPFRLSRDIVDGMGitGVEG----VFRRCCEKTMEVMRSSQ 2963
Cdd:cd05168   151 ILLDSE-GHIIHIDFGfmlsnspggLGF---------ETAPFKLTQEYVEVMG--GLESdmfrYFKTLMIQGFLALRKHA 218

                         250
                  ....*....|....
gi 755528316 2964 ETLLTIVEVLLYDP 2977
Cdd:cd05168   219 DRIVLLVEIMQQGS 232
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 2737-2994 1.18e-13

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: 74.22  E-value: 1.18e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2737 VKGRDDLRQDA-------VMQQVFQMCNTllqrntetrkrKLTICTYKVVPLSQRSGVLEWCtgtvpigeylvnsedgah 2809
Cdd:cd00893    32 VKTGDDLKQEQlalqlisQFDQIFKEEGL-----------PLWLRPYEILSLGPDSGIIEMI------------------ 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2810 rryrPNDFSANQCQKKMMEvqkksfeekYDTFMTICQNFEPVFRYFCMEKFLDpavwfekrlAYTRSVATSSIVGYILGL 2889
Cdd:cd00893    83 ----KNAVSIDSLKKKLDS---------FNKFVSLSDFFDDNFGDEAIQKARD---------NFLQSLVAYSLVCYFLQI 140

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2890 GDRHVQNILINEQsAELVHIDLGVAFEQgkilpTP-----ETVPFRLSRDIVDGMGITGVE--GVFRRCCEKTMEVMRSS 2962
Cdd:cd00893   141 KDRHNGNILLDKE-GHIIHIDFGFFLSS-----HPgfygfEGAPFKLSSEYIEVLGGVDSElfKEFRKLFLKGFMALRKH 214

                         250       260       270
                  ....*....|....*....|....*....|..
gi 755528316 2963 QETLLTIVEvLLYDPLFDWTMNPLKALYLQQR 2994
Cdd:cd00893   215 SDKILSLVE-MMYSGHGITCFGKKTIQQLKQR 245
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 2738-2975 5.43e-12

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: 69.54  E-value: 5.43e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2738 KGRDDLRQD-------AVMQQVFQMCNTllqrntetrkrKLTICTYKVVPLSQRSGVLEwctgtvpigeyLVnsedgahr 2810
Cdd:cd05167    55 KVGDDCRQDmlalqliSLFKNIFEEVGL-----------DLYLFPYRVVATGPGCGVIE-----------VI-------- 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2811 ryrPNDFSANQCQKkmmevqkksfeekydtfmticQNFEPVFRYFcMEKFLDP-AVWFEK-RLAYTRSVATSSIVGYILG 2888
Cdd:cd05167   105 ---PNSKSRDQIGR---------------------ETDNGLYEYF-LSKYGDEsTPAFQKaRRNFIKSMAGYSLVSYLLQ 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2889 LGDRHVQNILINEQsAELVHIDLGVAFEQ--GKILPTpETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVM---RSSQ 2963
Cdd:cd05167   160 IKDRHNGNIMIDDD-GHIIHIDFGFIFEIspGGNLGF-ESAPFKLTKEMVDLMGGSMESEPFKWFVELCVRGYlavRPYA 237

                         250
                  ....*....|..
gi 755528316 2964 ETLLTIVEVLLY 2975
Cdd:cd05167   238 EAIVSLVELMLD 249
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 3047-3076 1.57e-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: 1.57e-10
                           10        20        30
                   ....*....|....*....|....*....|
gi 755528316  3047 LSVGGQVNLLIQQAMDPKNLSRLFPGWKAW 3076
Cdd:pfam02260    2 LSVEGQVDELIQEATDPENLAQMYIGWCPW 31
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 2736-2974 9.86e-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: 60.36  E-value: 9.86e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2736 LVKGRDDLRQDAVMQQVFQMCNTLLQRntetRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEYLVNSEDGAhrryrpn 2815
Cdd:cd05173    98 IFKNGDDLRQDMLTLQILRLMDTLWKE----AGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQLNSSNVA------- 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2816 dfSANQCQKKMMEVQKKSFEEKYDtfmticqnfepvfryfcmekfLDPAVWfekrlAYTRSVATSSIVGYILGLGDRHVQ 2895
Cdd:cd05173   167 --AAAAFNKDALLNWLKEYNSGDD---------------------LERAIE-----EFTLSCAGYCVATYVLGIGDRHSD 218

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2896 NILInEQSAELVHIDLG--VAFEQGKILPTPETVPFRLSRDIVDGM--GITGVE---GVFRRCCEKTMEVMRSSQETLLT 2968
Cdd:cd05173   219 NIMV-RKNGQLFHIDFGhiLGNFKSKFGIKRERVPFILTYDFIHVIqqGKTGNTekfGRFRQYCEDAYLILRKNGNLFIT 297


                  ....*.
gi 755528316 2969 IVEVLL 2974
Cdd:cd05173   298 LFALML 303
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 2736-2960 1.10e-08

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: 60.06  E-value: 1.10e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2736 LVKGRDDLRQDAVMQQVFQMCNTLLQrnteTRKRKLTICTYKVVPLSQRSGVLEwctgtvpigeYLVNSEDGAHRRYRPN 2815
Cdd:cd05174   101 IFKNGDDLRQDMLTLQMIQLMDVLWK----QEGLDLRMTPYGCLSTGDKTGLIE----------VVLHSDTIANIQLNKS 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2816 DFSANQCQKKmmevqkksfeekyDTFMTICQNFEPvfryfcmEKFLDPAVwfEKrlaYTRSVATSSIVGYILGLGDRHVQ 2895
Cdd:cd05174   167 NMAATAAFNK-------------DALLNWLKSKNP-------GDALDQAI--EE---FTLSCAGYCVATYVLGIGDRHSD 221

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755528316 2896 NILINEqSAELVHIDLG--VAFEQGKILPTPETVPFRLSRDIVDGM--GITGVEGVFRR---CCEKTMEVMR 2960
Cdd:cd05174   222 NIMIRE-SGQLFHIDFGhfLGNFKTKFGINRERVPFILTYDFVHVIqqGKTNNSEKFERfrgYCERAYTILR 292
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2741-3004 3.53e-06

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: 51.91  E-value: 3.53e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2741 DDLRQDA-VMQQVFQMCNTLLQRNTEtrkrkLTICTYKVVPLSQRSGVLEwctgTVPIGEYLvnsedgahrryrpndfsa 2819
Cdd:cd05166    99 DDLRQDMlTLQLIRIMDKIWLQEGLD-----LKMITFRCVPTGNKRGMVE----LVPEAETL------------------ 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2820 nqcqkkmMEVQKK-----SFEEKydtfmTIcqnfepvfryfcmekfldpAVWFEK----RLAY-------TRSVATSSIV 2883
Cdd:cd05166   152 -------REIQTEhgltgSFKDR-----PL-------------------ADWLQKhnpsELEYekavenfIRSCAGYCVA 200

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2884 GYILGLGDRHVQNILInEQSAELVHIDLgvafeqGKILPTPET--------VPFRLSRD----IVDGMGITGVEGVFRRC 2951
Cdd:cd05166   201 TYVLGICDRHNDNIML-KTSGHLFHIDF------GKFLGDAQMfgnfkrdrVPFVLTSDmayvINGGDKPSSRFQLFVDL 273

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 755528316 2952 CEKTMEVMRSSQETLLTIVEVLLYDPLFDWTMNPLKALYLQQRPEDeSDLHST 3004
Cdd:cd05166   274 CCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQDDLRYVQDALLPEL-TDAEAT 325
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2741-2969 6.22e-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: 51.03  E-value: 6.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2741 DDLRQDAVMQQVFQMCNTLLQRntETRKRKLTIctYKVVPLSQRSGVLEwctgTVPigeylvNSEDGAHRRYRPNDFSAN 2820
Cdd:cd00891    96 DDLRQDQLTLQLLRIMDKLWKK--EGLDLRMTP--YKCIATGDEVGMIE----VVP------NSETTAAIQKKYGGFGAA 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2821 QCQKKMMEVQKK------SFEEKYDTFMTICQnfepvfryfcmekfldpavwfekrlAYTrsVATssivgYILGLGDRHV 2894
Cdd:cd00891   162 FKDTPISNWLKKhnpteeEYEEAVENFIRSCA-------------------------GYC--VAT-----YVLGIGDRHN 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2895 QNILINeQSAELVHIDlgvaFeqGKIL---PTP-----ETVPFRLSRDIVDGMGitGVEGV----FRRCCEKTMEVMRSS 2962
Cdd:cd00891   210 DNIMVT-KSGHLFHID----F--GHFLgnfKKKfgikrERAPFVFTPEMAYVMG--GEDSEnfqkFEDLCCKAYNILRKH 280


                  ....*..
gi 755528316 2963 QETLLTI 2969
Cdd:cd00891   281 GNLLINL 287
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2873-2961 1.63e-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: 1.63e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2873 YTRSVATSSIVGYILGLGDRHVQNILINEqSAELVHIDLgvafeqGKILP--------TPETVPFRLSRD----IVDGMG 2940
Cdd:cd05165   197 FTLSCAGYCVATYVLGIGDRHSDNIMVKE-NGQLFHIDF------GHFLGnfkkkfgiKRERVPFVLTHDfvyvIARGQD 269

                          90       100
                  ....*....|....*....|...
gi 755528316 2941 ITGVEGV--FRRCCEKTMEVMRS 2961
Cdd:cd05165   270 NTKSEEFqeFQELCEKAYLILRR 292
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 2873-3002 6.02e-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: 48.32  E-value: 6.02e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755528316 2873 YTRSVATSSIVGYILGLGDRHVQNILINEQsAELVHIDLGVAFEQGKIL--PTPETVPFRLSRDIVDGMGITGVEGV--- 2947
Cdd:cd00894   200 FVYSCAGYCVATFVLGIGDRHNDNIMITET-GNLFHIDFGHILGNYKSFlgINKERVPFVLTPDFLFVMGTSGKKTSlhf 278

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755528316 2948 --FRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWTMNP----LKALYLQQRPEDESDLH 3002
Cdd:cd00894   279 qkFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEdieyIRDALTVGKSEEDAKKH 339
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 2873-2936 9.37e-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: 9.37e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755528316 2873 YTRSVATSSIVGYILGLGDRHVQNILINEqSAELVHIDLG--VAFEQGKILPTPETVPFRLSRDIV 2936
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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