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Conserved domains on  [gi|1235902|gb|AAC50405|]
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FRAP-related protein [Homo sapiens]

Protein Classification

serine/threonine-protein kinase ATR( domain architecture ID 13925288)

serine/threonine-protein kinase ATR catalyzes the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates, and is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) family; it plays a central role in regulating the replication checkpoint

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 2293-2567 1.49e-155

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: 480.85  E-value: 1.49e-155
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLND 2372
Cdd:cd00892    1 ISGFEDEVEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2373 ECGIIEWVNNTAGLRPILTKLYkekgvymtgkelrqcmlpksaalseklkvfrefllprhPPIFHEWFLRTFPDPTSWYS 2452
Cdd:cd00892   81 ECGIIEWVPNTVTLRSILSTLY--------------------------------------PPVLHEWFLKNFPDPTAWYE 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2453 SRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLF 2532
Cdd:cd00892  123 ARNNYTRSTAVMSMVGYILGLGDRHGENILFDSTTGDVVHVDFDCLFDKGLTLEVPERVPFRLTQNMVDAMGVTGVEGTF 202

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 1235902  2533 RRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSK 2567
Cdd:cd00892  203 RRTCEVTLRVLRENRETLMSVLETFVHDPLVEWSR 237
TEL1 super family cl34875
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2133-2644 5.85e-91

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


The actual alignment was detected with superfamily member COG5032:

Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 331.75  E-value: 5.85e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2133 LAPYQFLTAFSQLISRICHSHDEvfvvlmeIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILNKAihMKKSLEKFV 2212
Cdd:COG5032 1634 LLHLLFEPILAQLLSRLSSENNK-------ISVALLIDKPLHEERENFPSGLSLSSFQSSFLKELIKKS--PRKIRKKFK 1704

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2213 GDATRLT-DKLLELCNKP--VDGSSSTLSMSTHFKMLKKLVEEAtFSEILIPLQSvmiptlpsilgthanhASHEPFPgh 2289
Cdd:COG5032 1705 IDISLLNlSRKLYISVLRsiRKRLKRLLELRLKKVSPKLLLFHA-FLEIKLPGQY----------------LLDKPFV-- 1765

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2290 waYIAGFDDMVEILAS-LQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVI 2368
Cdd:COG5032 1766 --LIERFEPEVSVVKShLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKVI 1843

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2369 PLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTGKELRQCMLpKSAALSEKLKVFREFLLpRHPPIFHEWFLRTFPDPT 2448
Cdd:COG5032 1844 PLSPGSGIIEWVPNSDTLHSILREYHKRKNISIDQEKKLAARL-DNLKLLLKDEFFTKATL-KSPPVLYDWFSESFPNPE 1921

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2449 SWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDF-NCLFNKGETFEVPEIVPFRLTHNMVNGMGPMG 2527
Cdd:COG5032 1922 DWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFgFILFNAPGRFPFPEKVPFRLTRNIVEAMGVSG 2001

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2528 TEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSKpVKGHSKAPLNETgevvnekakTHVLDIEQR-LQGviktR 2606
Cdd:COG5032 2002 VEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWRR-LPCFREIQNNEI---------VNVLERFRLkLSE----K 2067

                        490       500       510
                 ....*....|....*....|....*....|....*...
gi 1235902  2607 NRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGWTPYM 2644
Cdd:COG5032 2068 DAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPFW 2105
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 1771-2092 2.31e-63

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


:

Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 220.69  E-value: 2.31e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1771 NTYRVEAAWKLSQWDLVENYLAADgKSTTWSVRLGQLLLSAKKRDITAFYDSLKLVRAEQIVPLSAASFErgSYQRGYEY 1850
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLM-KKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGE--SYNRAYPL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1851 IVRLHMLCELEHSIKPLFQHSPGDSSQEDSL-NWVARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMVGECWLQSAR 1929
Cdd:pfam02259   78 LVRLQQLAELEEIIQYKQKLGQSSEELKSLLqTWRNRLPGCQDDVEIWQDILTVRSLVLSPIEDVYLGGYHAEMWLKFAN 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1930 VARKAGHHQTAYNALLNAGESR----LAELYVERAKWLWSKGDVHQALIVLQKGVELCFPENETPPEGKNM--------- 1996
Cdd:pfam02259  158 LARKSGRFSLAEKALLKLLGEDpeewLPEVVYAYAKYLWPTGEQQEALLKLREFLSCYLQKNGELLSGLEVinptnleef 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1997 --LIhGRAMLLVGRFMEET----ANFESNAIMKKYKDVTACLPEWEDGHFYLAKYYDKLMPMVTDNKMEK-QGDLIRYIV 2069
Cdd:pfam02259  238 teLL-ARCYLLKGKWQAALgqnwAEEKSEEILQAYLLATQFDPSWYKAWHTWALFNFEVLRKEEQGKEEEgPEDLSRYVV 316

                          330       340
                   ....*....|....*....|....*.
gi 1235902    2070 L---HFGRSLQYGNQFIYQSMPRMLT 2092
Cdd:pfam02259  317 PaveGYLRSLSLSSENSLQDTLRLLT 342
UME smart00802
Domain in UVSB PI-3 kinase, MEI-41 and ESR-1; Characteristic domain in UVSP PI-3 kinase, ...
 1119-1224 3.25e-30

Domain in UVSB PI-3 kinase, MEI-41 and ESR-1; Characteristic domain in UVSP PI-3 kinase, MEI-41 and ESR-1. Found in nucleolar proteins. Associated with FAT, FATC, PI3_PI4_kinase modules.


:

Pssm-ID: 214825  Cd Length: 107  Bit Score: 116.53  E-value: 3.25e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     1119 MADYLQPKLLGILAFFNMQLLSSS--VGIEDKKMALNSLMSLMKLMGpKHVSSVRVKMMTTLRTGLRfKDDFPELCCRAW 1196
Cdd:smart00802    1 LADFLKDHFLGILAVFSNILHDSSgkKPYNEKKRALRSIGFLIKLMG-KHISSALPQIMACLQSALE-IPELRSLALRCW 78

                            90       100
                    ....*....|....*....|....*...
gi 1235902     1197 DCFVRCLDHACLGSLLSHVIVALLPLIH 1224
Cdd:smart00802   79 HVLIKTLKEEELGPLLDQIFAAILPLWP 106
 
Name Accession Description Interval E-value
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 2293-2567 1.49e-155

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: 480.85  E-value: 1.49e-155
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLND 2372
Cdd:cd00892    1 ISGFEDEVEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2373 ECGIIEWVNNTAGLRPILTKLYkekgvymtgkelrqcmlpksaalseklkvfrefllprhPPIFHEWFLRTFPDPTSWYS 2452
Cdd:cd00892   81 ECGIIEWVPNTVTLRSILSTLY--------------------------------------PPVLHEWFLKNFPDPTAWYE 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2453 SRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLF 2532
Cdd:cd00892  123 ARNNYTRSTAVMSMVGYILGLGDRHGENILFDSTTGDVVHVDFDCLFDKGLTLEVPERVPFRLTQNMVDAMGVTGVEGTF 202

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 1235902  2533 RRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSK 2567
Cdd:cd00892  203 RRTCEVTLRVLRENRETLMSVLETFVHDPLVEWSR 237
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2324-2567 1.52e-92

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: 300.37  E-value: 1.52e-92
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     2324 MMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTG 2403
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     2404 kelrqcmLPKSAALSEKLKVFREFLLPRHPPIFHEWFLRTFPDP-TSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENIL 2482
Cdd:smart00146   81 -------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPsEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIM 153

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     2483 FDSlTGECVHVDFNCLFNKGETFEVP-EIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDP 2561
Cdd:smart00146  154 LDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDG 232


                    ....*.
gi 1235902     2562 LVEWSK 2567
Cdd:smart00146  233 LPDWRS 238
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2133-2644 5.85e-91

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 331.75  E-value: 5.85e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2133 LAPYQFLTAFSQLISRICHSHDEvfvvlmeIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILNKAihMKKSLEKFV 2212
Cdd:COG5032 1634 LLHLLFEPILAQLLSRLSSENNK-------ISVALLIDKPLHEERENFPSGLSLSSFQSSFLKELIKKS--PRKIRKKFK 1704

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2213 GDATRLT-DKLLELCNKP--VDGSSSTLSMSTHFKMLKKLVEEAtFSEILIPLQSvmiptlpsilgthanhASHEPFPgh 2289
Cdd:COG5032 1705 IDISLLNlSRKLYISVLRsiRKRLKRLLELRLKKVSPKLLLFHA-FLEIKLPGQY----------------LLDKPFV-- 1765

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2290 waYIAGFDDMVEILAS-LQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVI 2368
Cdd:COG5032 1766 --LIERFEPEVSVVKShLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKVI 1843

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2369 PLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTGKELRQCMLpKSAALSEKLKVFREFLLpRHPPIFHEWFLRTFPDPT 2448
Cdd:COG5032 1844 PLSPGSGIIEWVPNSDTLHSILREYHKRKNISIDQEKKLAARL-DNLKLLLKDEFFTKATL-KSPPVLYDWFSESFPNPE 1921

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2449 SWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDF-NCLFNKGETFEVPEIVPFRLTHNMVNGMGPMG 2527
Cdd:COG5032 1922 DWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFgFILFNAPGRFPFPEKVPFRLTRNIVEAMGVSG 2001

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2528 TEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSKpVKGHSKAPLNETgevvnekakTHVLDIEQR-LQGviktR 2606
Cdd:COG5032 2002 VEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWRR-LPCFREIQNNEI---------VNVLERFRLkLSE----K 2067

                        490       500       510
                 ....*....|....*....|....*....|....*...
gi 1235902  2607 NRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGWTPYM 2644
Cdd:COG5032 2068 DAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPFW 2105
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 2325-2566 3.91e-70

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: 236.07  E-value: 3.91e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    2325 MCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRelhIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKgvyMTGK 2404
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGENG---VPPT 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    2405 ELRQCMLPKSAALSEKLKvFREFLLPRHPPIFHEWFLRTFPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFD 2484
Cdd:pfam00454   79 AMVKILHSALNYPKLKLE-FESRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVD 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    2485 SLTGECVHVDFN-CLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLV 2563
Cdd:pfam00454  158 KTTGKLFHIDFGlCLPDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADGLP 237


                   ...
gi 1235902    2564 EWS 2566
Cdd:pfam00454  238 DWS 240
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 1771-2092 2.31e-63

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


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 220.69  E-value: 2.31e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1771 NTYRVEAAWKLSQWDLVENYLAADgKSTTWSVRLGQLLLSAKKRDITAFYDSLKLVRAEQIVPLSAASFErgSYQRGYEY 1850
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLM-KKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGE--SYNRAYPL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1851 IVRLHMLCELEHSIKPLFQHSPGDSSQEDSL-NWVARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMVGECWLQSAR 1929
Cdd:pfam02259   78 LVRLQQLAELEEIIQYKQKLGQSSEELKSLLqTWRNRLPGCQDDVEIWQDILTVRSLVLSPIEDVYLGGYHAEMWLKFAN 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1930 VARKAGHHQTAYNALLNAGESR----LAELYVERAKWLWSKGDVHQALIVLQKGVELCFPENETPPEGKNM--------- 1996
Cdd:pfam02259  158 LARKSGRFSLAEKALLKLLGEDpeewLPEVVYAYAKYLWPTGEQQEALLKLREFLSCYLQKNGELLSGLEVinptnleef 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1997 --LIhGRAMLLVGRFMEET----ANFESNAIMKKYKDVTACLPEWEDGHFYLAKYYDKLMPMVTDNKMEK-QGDLIRYIV 2069
Cdd:pfam02259  238 teLL-ARCYLLKGKWQAALgqnwAEEKSEEILQAYLLATQFDPSWYKAWHTWALFNFEVLRKEEQGKEEEgPEDLSRYVV 316

                          330       340
                   ....*....|....*....|....*.
gi 1235902    2070 L---HFGRSLQYGNQFIYQSMPRMLT 2092
Cdd:pfam02259  317 PaveGYLRSLSLSSENSLQDTLRLLT 342
UME smart00802
Domain in UVSB PI-3 kinase, MEI-41 and ESR-1; Characteristic domain in UVSP PI-3 kinase, ...
 1119-1224 3.25e-30

Domain in UVSB PI-3 kinase, MEI-41 and ESR-1; Characteristic domain in UVSP PI-3 kinase, MEI-41 and ESR-1. Found in nucleolar proteins. Associated with FAT, FATC, PI3_PI4_kinase modules.


Pssm-ID: 214825  Cd Length: 107  Bit Score: 116.53  E-value: 3.25e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     1119 MADYLQPKLLGILAFFNMQLLSSS--VGIEDKKMALNSLMSLMKLMGpKHVSSVRVKMMTTLRTGLRfKDDFPELCCRAW 1196
Cdd:smart00802    1 LADFLKDHFLGILAVFSNILHDSSgkKPYNEKKRALRSIGFLIKLMG-KHISSALPQIMACLQSALE-IPELRSLALRCW 78

                            90       100
                    ....*....|....*....|....*...
gi 1235902     1197 DCFVRCLDHACLGSLLSHVIVALLPLIH 1224
Cdd:smart00802   79 HVLIKTLKEEELGPLLDQIFAAILPLWP 106
UME pfam08064
UME (NUC010) domain; This domain is characteriztic of UVSB PI-3 kinase, MEI-41 and ESR1.
 1122-1223 4.39e-27

UME (NUC010) domain; This domain is characteriztic of UVSB PI-3 kinase, MEI-41 and ESR1.


Pssm-ID: 462350  Cd Length: 102  Bit Score: 107.19  E-value: 4.39e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1122 YLQPKLLGILAFFNMQLLSSSV--GIEDKKMALNSLMSLMKLMGPkHVSSVRVKMMTTLRTGLRfKDDFPELCCRAWDCF 1199
Cdd:pfam08064    1 FLENHILGILARFSDVLNDLRGkkPVEEKKRALRSIEELIKLMGS-AISSALPQIMACLQSALE-IPELREVALSCWDAF 78

                           90       100
                   ....*....|....*....|....
gi 1235902    1200 VRCLDHACLGSLLSHVIVALLPLI 1223
Cdd:pfam08064   79 VKTLDEEDLGPLLDQTFAAILQLW 102
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 2613-2644 3.11e-12

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: 62.78  E-value: 3.11e-12
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1235902    2613 PLSIEGHVHYLIQEATDENLLCQMYLGWTPYM 2644
Cdd:pfam02260    1 PLSVEGQVDELIQEATDPENLAQMYIGWCPWW 32
 
Name Accession Description Interval E-value
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 2293-2567 1.49e-155

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: 480.85  E-value: 1.49e-155
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLND 2372
Cdd:cd00892    1 ISGFEDEVEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2373 ECGIIEWVNNTAGLRPILTKLYkekgvymtgkelrqcmlpksaalseklkvfrefllprhPPIFHEWFLRTFPDPTSWYS 2452
Cdd:cd00892   81 ECGIIEWVPNTVTLRSILSTLY--------------------------------------PPVLHEWFLKNFPDPTAWYE 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2453 SRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLF 2532
Cdd:cd00892  123 ARNNYTRSTAVMSMVGYILGLGDRHGENILFDSTTGDVVHVDFDCLFDKGLTLEVPERVPFRLTQNMVDAMGVTGVEGTF 202

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 1235902  2533 RRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSK 2567
Cdd:cd00892  203 RRTCEVTLRVLRENRETLMSVLETFVHDPLVEWSR 237
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 2293-2560 5.69e-115

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: 363.90  E-value: 5.69e-115
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLND 2372
Cdd:cd05164    1 IASFDPRVRILASLQKPKKITILGSDGKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKETRKRNLTIRTYSVVPLSS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2373 ECGIIEWVNNTAGLRPIltklykekgvymtgkelrqcmlpksaalseklkvfrefllprhppiFHEWFLRTFPDPTSWYS 2452
Cdd:cd05164   81 QSGLIEWVDNTTTLKPV----------------------------------------------LKKWFNETFPDPTQWYE 114

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2453 SRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLF 2532
Cdd:cd05164  115 ARSNYTKSTAVMSMVGYIIGLGDRHLENILIDTKTGEVVHIDFGMIFNKGKTLPVPEIVPFRLTRNIINGMGPTGVEGLF 194

                        250       260
                 ....*....|....*....|....*...
gi 1235902  2533 RRACEVTMRLMRDQREPLMSVLKTFLHD 2560
Cdd:cd05164  195 RKSCEQVLRVFRKHKDKLITFLDTFLYD 222
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 2293-2566 3.22e-100

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: 324.11  E-value: 3.22e-100
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCrLME--FnSLINKCLRKDAESRRRELHIRTYAVIPL 2370
Cdd:cd05171    1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQDA-VMEqvF-ELVNQLLKRDKETRKRKLRIRTYKVVPL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2371 NDECGIIEWVNNTAGLRPILTKLYKEKGV-------YMTGKELRQCMLPKS-AALSEKLKVFREfLLPRHPPIFHEWFLR 2442
Cdd:cd05171   79 SPRSGVLEFVENTIPLGEYLVGASSKSGAharyrpkDWTASTCRKKMREKAkASAEERLKVFDE-ICKNFKPVFRHFFLE 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2443 TFPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNG 2522
Cdd:cd05171  158 KFPDPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQGKLLPIPETVPFRLTRDIVDG 237

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 1235902  2523 MGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWS 2566
Cdd:cd05171  238 MGITGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWT 281
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 2324-2567 1.52e-92

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: 300.37  E-value: 1.52e-92
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     2324 MMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTG 2403
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGKVLDL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     2404 kelrqcmLPKSAALSEKLKVFREFLLPRHPPIFHEWFLRTFPDP-TSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENIL 2482
Cdd:smart00146   81 -------RSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDPsEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIM 153

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     2483 FDSlTGECVHVDFNCLFNKGETFEVP-EIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDP 2561
Cdd:smart00146  154 LDK-TGHLFHIDFGFILGNGPKLFGFpERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDG 232


                    ....*.
gi 1235902     2562 LVEWSK 2567
Cdd:smart00146  233 LPDWRS 238
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
2133-2644 5.85e-91

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 331.75  E-value: 5.85e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2133 LAPYQFLTAFSQLISRICHSHDEvfvvlmeIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILNKAihMKKSLEKFV 2212
Cdd:COG5032 1634 LLHLLFEPILAQLLSRLSSENNK-------ISVALLIDKPLHEERENFPSGLSLSSFQSSFLKELIKKS--PRKIRKKFK 1704

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2213 GDATRLT-DKLLELCNKP--VDGSSSTLSMSTHFKMLKKLVEEAtFSEILIPLQSvmiptlpsilgthanhASHEPFPgh 2289
Cdd:COG5032 1705 IDISLLNlSRKLYISVLRsiRKRLKRLLELRLKKVSPKLLLFHA-FLEIKLPGQY----------------LLDKPFV-- 1765

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2290 waYIAGFDDMVEILAS-LQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVI 2368
Cdd:COG5032 1766 --LIERFEPEVSVVKShLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDLWIRPYKVI 1843

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2369 PLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTGKELRQCMLpKSAALSEKLKVFREFLLpRHPPIFHEWFLRTFPDPT 2448
Cdd:COG5032 1844 PLSPGSGIIEWVPNSDTLHSILREYHKRKNISIDQEKKLAARL-DNLKLLLKDEFFTKATL-KSPPVLYDWFSESFPNPE 1921

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2449 SWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDF-NCLFNKGETFEVPEIVPFRLTHNMVNGMGPMG 2527
Cdd:COG5032 1922 DWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFgFILFNAPGRFPFPEKVPFRLTRNIVEAMGVSG 2001

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2528 TEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSKpVKGHSKAPLNETgevvnekakTHVLDIEQR-LQGviktR 2606
Cdd:COG5032 2002 VEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWRR-LPCFREIQNNEI---------VNVLERFRLkLSE----K 2067

                        490       500       510
                 ....*....|....*....|....*....|....*...
gi 1235902  2607 NRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGWTPYM 2644
Cdd:COG5032 2068 DAEKFVDLLINKSVESLITQATDPFQLATMYIGWMPFW 2105
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 2293-2566 4.73e-79

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: 263.19  E-value: 4.73e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLND 2372
Cdd:cd05169    1 ISSFDPTLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDERVMQLFGLVNTLLKNDSETSRRNLSIQRYSVIPLSP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2373 ECGIIEWVNNTAGLRPILTKLYKEKGVYMTgKELRqCMLPKSAA-----LSEKLKVFREFLlpRHPP------IFheWfL 2441
Cdd:cd05169   81 NSGLIGWVPGCDTLHSLIRDYREKRKIPLN-IEHR-LMLQMAPDydnltLIQKVEVFEYAL--ENTPgddlrrVL--W-L 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2442 RTfPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFnclfnkGETFEV-------PEIVPFR 2514
Cdd:cd05169  154 KS-PSSEAWLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLTGKVIHIDF------GDCFEVamhrekfPEKVPFR 226

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 1235902  2515 LTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWS 2566
Cdd:cd05169  227 LTRMLVNAMEVSGVEGTFRSTCEDVMRVLRENKDSLMAVLEAFVHDPLISWR 278
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 2293-2567 3.03e-77

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: 259.11  E-value: 3.03e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLND 2372
Cdd:cd05170    1 IQSVGSTVTVLPTKTKPKKLVFLGSDGKRYPYLFKGLEDLHLDERIMQFLSIVNAMLASDNEHRRRRYRARHYSVTPLGP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2373 ECGIIEWVNNTAGLRPILTKLYKEKGVYMTGKELR----QCMLPK---------SAALSEK----------------LKV 2423
Cdd:cd05170   81 RSGLIQWVDGATPLFSLYKRWQQRRAAAQAQKNQDsgstPPPVPRpselfynklKPALKAAgirkstsrrewplevlRQV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2424 FREFLLPRHPPIFH-EWFLRTfPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKG 2502
Cdd:cd05170  161 LEELVAETPRDLLArELWCSS-PSSAEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDLSTGEVVHIDYNVCFEKG 239

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1235902  2503 ETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSK 2567
Cdd:cd05170  240 KRLRVPEKVPFRLTQNIEHALGPTGVEGTFRLSCEQVLKILRKGRETLLTLLEAFVYDPLVDWTA 304
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 2325-2566 3.91e-70

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: 236.07  E-value: 3.91e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    2325 MCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRelhIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKgvyMTGK 2404
Cdd:pfam00454    5 IYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGENG---VPPT 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    2405 ELRQCMLPKSAALSEKLKvFREFLLPRHPPIFHEWFLRTFPDPTSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFD 2484
Cdd:pfam00454   79 AMVKILHSALNYPKLKLE-FESRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVD 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    2485 SLTGECVHVDFN-CLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLV 2563
Cdd:pfam00454  158 KTTGKLFHIDFGlCLPDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADGLP 237


                   ...
gi 1235902    2564 EWS 2566
Cdd:pfam00454  238 DWS 240
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 2293-2567 1.55e-66

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: 225.53  E-value: 1.55e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLND 2372
Cdd:cd05172    1 IVGFDPRVLVLSSKRRPKRITIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDPACRQRRLRIRTYQVIPMTS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2373 ECGIIEWVNNTAGLRPILTKlykekgvymtgkelrqcmlpksaalseklKVFREFllprhppifhewFLRTFPDPTSWYS 2452
Cdd:cd05172   81 RLGLIEWVDNTTPLKEILEN-----------------------------DLLRRA------------LLSLASSPEAFLA 119

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2453 SRSAYCRSTAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETF-EVPEIVPFRLTHNMVNGMGPMGTEGL 2531
Cdd:cd05172  120 LRSNFARSLAAMSICGYILGIGDRHLSNFLVDLSTGRLIGIDFGHAFGSATQFlPIPELVPFRLTRQLLNLLQPLDARGL 199

                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 1235902  2532 FRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSK 2567
Cdd:cd05172  200 LRSDMVHVLRALRAGRDLLLATMDVFVKEPLLDWQK 235
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 1771-2092 2.31e-63

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


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 220.69  E-value: 2.31e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1771 NTYRVEAAWKLSQWDLVENYLAADgKSTTWSVRLGQLLLSAKKRDITAFYDSLKLVRAEQIVPLSAASFErgSYQRGYEY 1850
Cdd:pfam02259    1 APLAAEAAWRLGQWDLMREYLSLM-KKDSPDKAFFEAILALHRNQFDEAERYIEKARQLLDTELSALSGE--SYNRAYPL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1851 IVRLHMLCELEHSIKPLFQHSPGDSSQEDSL-NWVARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMVGECWLQSAR 1929
Cdd:pfam02259   78 LVRLQQLAELEEIIQYKQKLGQSSEELKSLLqTWRNRLPGCQDDVEIWQDILTVRSLVLSPIEDVYLGGYHAEMWLKFAN 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1930 VARKAGHHQTAYNALLNAGESR----LAELYVERAKWLWSKGDVHQALIVLQKGVELCFPENETPPEGKNM--------- 1996
Cdd:pfam02259  158 LARKSGRFSLAEKALLKLLGEDpeewLPEVVYAYAKYLWPTGEQQEALLKLREFLSCYLQKNGELLSGLEVinptnleef 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1997 --LIhGRAMLLVGRFMEET----ANFESNAIMKKYKDVTACLPEWEDGHFYLAKYYDKLMPMVTDNKMEK-QGDLIRYIV 2069
Cdd:pfam02259  238 teLL-ARCYLLKGKWQAALgqnwAEEKSEEILQAYLLATQFDPSWYKAWHTWALFNFEVLRKEEQGKEEEgPEDLSRYVV 316

                          330       340
                   ....*....|....*....|....*.
gi 1235902    2070 L---HFGRSLQYGNQFIYQSMPRMLT 2092
Cdd:pfam02259  317 PaveGYLRSLSLSSENSLQDTLRLLT 342
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 2302-2560 1.19e-37

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: 141.70  E-value: 1.19e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2302 ILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDaesrRRELHIRTYAVIPLNDECGIIEWVN 2381
Cdd:cd00142   10 VIHSKQRPKKITLIGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKE----SVNLVLPPYKVIPLSENSGLIEIVK 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2382 NTaglrpiltklykekgvymtgkelrqcmlpksaalseklkVFREFLLprhppifhEWFLRTFPDPTSWYSSRSAYCRST 2461
Cdd:cd00142   86 DA---------------------------------------QTIEDLL--------KSLWRKSPSSQSWLNRRENFSCSL 118

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2462 AVMSMVGYILGLGDRHGENILFDSlTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMR 2541
Cdd:cd00142  119 AGYSVLGYIFGIGDRHPSNIMIEP-SGNIFHIDFGFIFSGRKLAEGVETVPFRLTPMLENAMGTAGVNGPFQISMVKIME 197

                        250
                 ....*....|....*....
gi 1235902  2542 LMRDQREPLMSVLKTFLHD 2560
Cdd:cd00142  198 ILREHADLIVPILEHSLRD 216
UME smart00802
Domain in UVSB PI-3 kinase, MEI-41 and ESR-1; Characteristic domain in UVSP PI-3 kinase, ...
 1119-1224 3.25e-30

Domain in UVSB PI-3 kinase, MEI-41 and ESR-1; Characteristic domain in UVSP PI-3 kinase, MEI-41 and ESR-1. Found in nucleolar proteins. Associated with FAT, FATC, PI3_PI4_kinase modules.


Pssm-ID: 214825  Cd Length: 107  Bit Score: 116.53  E-value: 3.25e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902     1119 MADYLQPKLLGILAFFNMQLLSSS--VGIEDKKMALNSLMSLMKLMGpKHVSSVRVKMMTTLRTGLRfKDDFPELCCRAW 1196
Cdd:smart00802    1 LADFLKDHFLGILAVFSNILHDSSgkKPYNEKKRALRSIGFLIKLMG-KHISSALPQIMACLQSALE-IPELRSLALRCW 78

                            90       100
                    ....*....|....*....|....*...
gi 1235902     1197 DCFVRCLDHACLGSLLSHVIVALLPLIH 1224
Cdd:smart00802   79 HVLIKTLKEEELGPLLDQIFAAILPLWP 106
UME pfam08064
UME (NUC010) domain; This domain is characteriztic of UVSB PI-3 kinase, MEI-41 and ESR1.
 1122-1223 4.39e-27

UME (NUC010) domain; This domain is characteriztic of UVSB PI-3 kinase, MEI-41 and ESR1.


Pssm-ID: 462350  Cd Length: 102  Bit Score: 107.19  E-value: 4.39e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902    1122 YLQPKLLGILAFFNMQLLSSSV--GIEDKKMALNSLMSLMKLMGPkHVSSVRVKMMTTLRTGLRfKDDFPELCCRAWDCF 1199
Cdd:pfam08064    1 FLENHILGILARFSDVLNDLRGkkPVEEKKRALRSIEELIKLMGS-AISSALPQIMACLQSALE-IPELREVALSCWDAF 78

                           90       100
                   ....*....|....*....|....
gi 1235902    1200 VRCLDHACLGSLLSHVIVALLPLI 1223
Cdd:pfam08064   79 VKTLDEEDLGPLLDQTFAAILQLW 102
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 2310-2567 1.00e-22

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: 99.90  E-value: 1.00e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2310 KKISLKGSDGK---FYIMMCKPKDdLRKDCRLMEFNSLINKCLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGL 2386
Cdd:cd05163   19 RRLTIRGHDGSkypFLVQTPSARH-SRREERVMQLFRLLNRVLERKKETRRRNLQFHVPIVVPLSPQVRLVEDDPSYISL 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2387 RPIltklYKEKGVYmtgKELRQCMLPKSaalseklkvfrefllprhppIFHEWFLRTFPDPTSWYSSRSAYCRSTAVMSM 2466
Cdd:cd05163   98 QDI----YEKLEIL---NEIQSKMVPET--------------------ILSNYFLRTMPSPSDLWLFRKQFTLQLALSSF 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2467 VGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGE-TFEVPEIVPFRLTHNMVNGMGPMGTEGLFRRACEVTMR-LMR 2544
Cdd:cd05163  151 MTYVLSLGNRTPHRILISRSTGNVFMTDFLPSINSQGpLLDNNEPVPFRLTPNIQHFIGPIGVEGLLTSSMMAIARaLTE 230

                        250       260
                 ....*....|....*....|...
gi 1235902  2545 DQREpLMSVLKTFLHDPLVEWSK 2567
Cdd:cd05163  231 PEYD-LEQYLSLFVRDELISWHK 252
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2214-2536 6.68e-18

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: 87.97  E-value: 6.68e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2214 DATRLTDKLLELCNKPVDGSSSTLSMSTHFK-MLKKLVEEATFSEILIPLqsvmiPTLPSIlgthanhashepfpghwaY 2292
Cdd:cd00896    6 RQQEFVDRLRSLMKEVKNEKGSRDKKIERLReLLSDSELGLLLFFEPLPL-----PLDPSV------------------K 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2293 IAGFD-DMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDaesrRRELHIRTYAVIPLN 2371
Cdd:cd00896   63 VTGIIpEKSTVFKSALMPLKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKE----NLDLKLTPYKVLATS 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2372 DECGIIEWVNNTAGLRPILTKlykekgvymtGKELRQcmlpksaalseklkvfrefllprhppifhewFLRTF-PDPTSW 2450
Cdd:cd00896  139 PNDGLVEFVPNSKALADILKK----------YGSILN-------------------------------FLRKHnPDESGP 177

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2451 YSSRSA----YCRSTAVMSMVGYILGLGDRHGENILFDSlTGECVHVDFNCLFNKGETFEVPeivPFRLTHNMVNGMGPM 2526
Cdd:cd00896  178 YGIKPEvmdnFVKSCAGYCVITYILGVGDRHLDNLLLTK-DGHLFHIDFGYILGRDPKPFPP---PMKLCKEMVEAMGGA 253

                        330
                 ....*....|..
gi 1235902  2527 GTEG--LFRRAC 2536
Cdd:cd00896  254 NSEGykEFKKYC 265
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2304-2559 1.15e-15

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: 81.18  E-value: 1.15e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2304 ASLQKPKKISLKGSD--GKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDaesrRRELHIRTYAVIPLNDECGIIEWVN 2381
Cdd:cd05166   71 NSNALPLKLVFRNADprAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQE----GLDLKMITFRCVPTGNKRGMVELVP 146

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2382 NTAGLRPILTklykEKGVymTGkelrqcmlpksaalseklkVFREFLLprhppifHEWFLRTFPDPTSWYSSRSAYCRST 2461
Cdd:cd05166  147 EAETLREIQT----EHGL--TG-------------------SFKDRPL-------ADWLQKHNPSELEYEKAVENFIRSC 194

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2462 AVMSMVGYILGLGDRHGENILFDSlTGECVHVDFNCLFNKGETFeVP---EIVPFRLTHNMV----NGMGPMGTEGLFRR 2534
Cdd:cd05166  195 AGYCVATYVLGICDRHNDNIMLKT-SGHLFHIDFGKFLGDAQMF-GNfkrDRVPFVLTSDMAyvinGGDKPSSRFQLFVD 272

                        250       260
                 ....*....|....*....|....*
gi 1235902  2535 ACEVTMRLMRDQREPLMSVLKTFLH 2559
Cdd:cd05166  273 LCCQAFNIIRKNSNLLLNLLSLMLS 297
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 2613-2644 3.11e-12

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: 62.78  E-value: 3.11e-12
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1235902    2613 PLSIEGHVHYLIQEATDENLLCQMYLGWTPYM 2644
Cdd:pfam02260    1 PLSVEGQVDELIQEATDPENLAQMYIGWCPWW 32
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 2327-2541 3.14e-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: 69.93  E-value: 3.14e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2327 KPKDDLRKDCRLMEFNSLinkcLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPIltklykekgvymtGKEl 2406
Cdd:cd05167   55 KVGDDCRQDMLALQLISL----FKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQI-------------GRE- 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2407 rqcmlpksaalseklkvfREFLLprhppifHEWFLRTFPDP--TSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFD 2484
Cdd:cd05167  117 ------------------TDNGL-------YEYFLSKYGDEstPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMID 171

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1235902  2485 SlTGECVHVDFNCLF------NKGetFEVPeivPFRLTHNMVNGMGPMGTEGLFRRACEVTMR 2541
Cdd:cd05167  172 D-DGHIIHIDFGFIFeispggNLG--FESA---PFKLTKEMVDLMGGSMESEPFKWFVELCVR 228
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2308-2537 1.40e-10

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: 65.28  E-value: 1.40e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2308 KPKKISLKGSD--GKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAesrrRELHIRTYAVIPLNDECGIIEWVNNTAG 2385
Cdd:cd00891   72 LPLWLVFKNADpgGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEG----LDLRMTPYKCIATGDEVGMIEVVPNSET 147

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2386 LRPILtklYKEKGVymtgkelrqcmlpkSAALSEKlkvfrefllprhppIFHEWFLRTFPDPTSW-------YSSRSAYC 2458
Cdd:cd00891  148 TAAIQ---KKYGGF--------------GAAFKDT--------------PISNWLKKHNPTEEEYeeavenfIRSCAGYC 196

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2459 RSTavmsmvgYILGLGDRHGENILFDSlTGECVHVDF-NCLFNKGETFEVP-EIVPFRLTHNMVNGMGpmGTEGL-FRRA 2535
Cdd:cd00891  197 VAT-------YVLGIGDRHNDNIMVTK-SGHLFHIDFgHFLGNFKKKFGIKrERAPFVFTPEMAYVMG--GEDSEnFQKF 266


                 ..
gi 1235902  2536 CE 2537
Cdd:cd00891  267 ED 268
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 2327-2524 2.31e-09

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: 61.12  E-value: 2.31e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2327 KPKDDLRKDCRLMEFNSLINKCLRKdaESRRreLHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKGVYMtgkel 2406
Cdd:cd00893   33 KTGDDLKQEQLALQLISQFDQIFKE--EGLP--LWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKLDSFNKFVS----- 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2407 rqcmlpksaalseklkvFREFllprhppifhewFLRTFPDPtSWYSSRSAYCRSTAVMSMVGYILGLGDRHGENILFDSl 2486
Cdd:cd00893  104 -----------------LSDF------------FDDNFGDE-AIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDK- 152

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 1235902  2487 TGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMVNGMG 2524
Cdd:cd00893  153 EGHIIHIDFGFFLSSHPGFYGFEGAPFKLSSEYIEVLG 190
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 2324-2536 1.20e-07

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: 55.95  E-value: 1.20e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2324 MMCKPKDDLRKDCRLMEfnsLINKClrKDA-ESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPIltklyKEKGVYMT 2402
Cdd:cd05168   33 VIVKSGDDLRQELLAMQ---LIKQF--QRIfEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSL-----KKRFPNFT 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2403 GkeLRQCmlpksaalseklkvfrefllprhppifhewFLRTFPDPTS--WYSSRSAYCRSTAVMSMVGYILGLGDRHGEN 2480
Cdd:cd05168  103 S--LLDY------------------------------FERTFGDPNSerFKEAQRNFVESLAAYSLVCYLLQIKDRHNGN 150

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1235902  2481 ILFDSlTGECVHVDFNCLFN---KGETFEVpeiVPFRLTHNMVNGMGPMGTEG--LFRRAC 2536
Cdd:cd05168  151 ILLDS-EGHIIHIDFGFMLSnspGGLGFET---APFKLTQEYVEVMGGLESDMfrYFKTLM 207
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 2327-2544 5.15e-07

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: 54.58  E-value: 5.15e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2327 KPKDDLRKDCRLMEFNSLINkCLRKDAEsrrRELHIRTYAVIPLNDECGIIEWVNNTAGLRPIltklykekgvymtgkEL 2406
Cdd:cd05173  100 KNGDDLRQDMLTLQILRLMD-TLWKEAG---LDLRIVPYGCLATGDRSGLIEVVSSAETIADI---------------QL 160

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2407 RQCMLPKSAALSEKlkVFREFLLPRHPPIFHEWFLRTFPdptswySSRSAYCRSTavmsmvgYILGLGDRHGENILFDSl 2486
Cdd:cd05173  161 NSSNVAAAAAFNKD--ALLNWLKEYNSGDDLERAIEEFT------LSCAGYCVAT-------YVLGIGDRHSDNIMVRK- 224

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1235902  2487 TGECVHVDF-NCLFNKGETFEVP-EIVPFRLTHNMVNGM--GPMG-TE--GLFRRACEVTMRLMR 2544
Cdd:cd05173  225 NGQLFHIDFgHILGNFKSKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQYCEDAYLILR 289
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 2223-2544 8.47e-07

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: 53.90  E-value: 8.47e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2223 LELCNKPVDGSSSTLSMSTHFKMLKKLVEEATFSEILIPLQSvmiPTLPSILGTHAnhashepfpghwayiagFDDMVEI 2302
Cdd:cd05174   17 MKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQS---PLDPSIILEEV-----------------CVDQCTF 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2303 LASLQKPKKISLK----GSDGKFYIMmcKPKDDLRKDCRLMEFNSLINKCLRKDAesrrRELHIRTYAVIPLNDECGIIE 2378
Cdd:cd05174   77 MDSKMKPLWIMYSseeaGAGNVGIIF--KNGDDLRQDMLTLQMIQLMDVLWKQEG----LDLRMTPYGCLSTGDKTGLIE 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2379 WVNNTAGLRPIltklykekgvymtgkELRQCMLPKSAALSEKlkVFREFLLPRHPPIFHEWFLRTFPdptswySSRSAYC 2458
Cdd:cd05174  151 VVLHSDTIANI---------------QLNKSNMAATAAFNKD--ALLNWLKSKNPGDALDQAIEEFT------LSCAGYC 207

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2459 RSTavmsmvgYILGLGDRHGENILFDSlTGECVHVDF-NCLFNKGETFEVP-EIVPFRLTHNMVNGMGPMGTEG-----L 2531
Cdd:cd05174  208 VAT-------YVLGIGDRHSDNIMIRE-SGQLFHIDFgHFLGNFKTKFGINrERVPFILTYDFVHVIQQGKTNNsekfeR 279

                        330
                 ....*....|...
gi 1235902  2532 FRRACEVTMRLMR 2544
Cdd:cd05174  280 FRGYCERAYTILR 292
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 2301-2546 2.24e-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: 49.17  E-value: 2.24e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2301 EILASLQKPKKISLKGSD-----GKFYIMMCKPKDDLRKD------CRLMEfnsLINKCLRKDaesrrreLHIRTYAVIP 2369
Cdd:cd05165   70 KVMDSKKRPLWLVFENADplalsGEDIKIIFKNGDDLRQDmltlqiIRIMD---NIWKEEGLD-------LRMLPYGCLS 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2370 LNDECGIIEWVNNTAGLRPILTKLYKEKGVYMTGKELRQCMLPKSAALSEKLKVFREFLLprhppifhewflrtfpdpts 2449
Cdd:cd05165  140 TGDNVGLIEVVRNAKTIANIQKKKGKVATLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTL-------------------- 199

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2450 wysSRSAYCRSTavmsmvgYILGLGDRHGENILFDSlTGECVHVDF-NCLFNKGETFEVP-EIVPFRLTHNMV----NGM 2523
Cdd:cd05165  200 ---SCAGYCVAT-------YVLGIGDRHSDNIMVKE-NGQLFHIDFgHFLGNFKKKFGIKrERVPFVLTHDFVyviaRGQ 268

                        250       260
                 ....*....|....*....|....*
gi 1235902  2524 GPMGTEGL--FRRACEVTMRLMRDQ 2546
Cdd:cd05165  269 DNTKSEEFqeFQELCEKAYLILRRH 293
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 2309-2564 5.73e-05

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


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 48.05  E-value: 5.73e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2309 PKKISLKGSD--GKFYIMMCKPKDDLRKDCRLMEFNSLINKCLRKDAesrrRELHIRTYAVIPLNDECGIIEWVNNTAGL 2386
Cdd:cd05176   76 PLKVALVNADplGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEG----LDLRMVIFKCLSTGKDRGMVELVPSSDTL 151

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2387 RpiltKLYKEKGVymTGKelrqcmlpksaalseklkvFREFLLPrhppifhEWFLRTFPDPTSWYSSRSAYCRSTAVMSM 2466
Cdd:cd05176  152 R----KIQVEYGV--TGS-------------------FKDKPLA-------EWLRKYNPSEEEYEKASENFIYSCAGCCV 199

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2467 VGYILGLGDRHGENILFDSlTGECVHVDFNCLFNKGETFEV--PEIVPFRLTHNMV----NGMGPMGTEGLFRRACEVTM 2540
Cdd:cd05176  200 ATYVLGICDRHNDNIMLRS-TGHMFHIDFGKFLGHAQMFGSfkRDRAPFVLTSDMAyvinGGEKPTIRFQLFVDLCCQAY 278

                        250       260
                 ....*....|....*....|....
gi 1235902  2541 RLMRDQREPLMSVLKTFLHDPLVE 2564
Cdd:cd05176  279 NLIRKHTNLFLNLLSLMLSSGLPE 302
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 2301-2527 1.14e-03

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: 44.08  E-value: 1.14e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2301 EILASLQKPKKISLKGSDGKFYI-----MMCKPKDDLRKDCRLMEfnslINKCLRKDAESRRRELHIRTYAVIPLNDECG 2375
Cdd:cd00894   74 KVMASKKKPLWLEFKCADPTALSnetigIIFKHGDDLRQDMLILQ----ILRIMESIWETESLDLCLLPYGCISTGDKIG 149

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1235902  2376 IIEWVNNTAGLRPILTKLYKEKGVYmtgkelrqcmlpKSAALSEKLKvfrefllpRHPPIFHEWFLRTfpdpTSWYSSRS 2455
Cdd:cd00894  150 MIEIVKDATTIAKIQQSTVGNTGAF------------KDEVLNHWLK--------EKCPIEEKFQAAV----ERFVYSCA 205

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1235902  2456 AYCRSTavmsmvgYILGLGDRHGENILFdSLTGECVHVDFNCLFNKGETFE--VPEIVPFRLTHNMVNGMGPMG 2527
Cdd:cd00894  206 GYCVAT-------FVLGIGDRHNDNIMI-TETGNLFHIDFGHILGNYKSFLgiNKERVPFVLTPDFLFVMGTSG 271
 
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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