NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|1778029372|ref|XP_031551906|]
View 

serine/threonine-protein kinase mTOR-like [Actinia tenebrosa]

Protein Classification

PIKK family serine/threonine-protein kinase( domain architecture ID 13414812)

phosphoinositide 3-kinase-related protein kinase (PIKK) family serine/threonine-protein kinase has intrinsic serine/threonine kinase activity and is distinguished from other PKs by its unique catalytic domain that is similar to that of lipid PI3K

CATH:  1.10.510.10
EC:  2.7.11.1
Gene Ontology:  GO:0004674|GO:0006468|GO:0005524
PubMed:  15279773|19614568|16244704

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 406-684 0e+00

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: 613.34  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 406 IRHVHSSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLST 485
Cdd:cd05169     1 ISSFDPTLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDERVMQLFGLVNTLLKNDSETSRRNLSIQRYSVIPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 486 NSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMEKVEVFEHALANTNGDDLAKLLWLKSPSSEV 565
Cdd:cd05169    81 NSGLIGWVPGCDTLHSLIRDYREKRKIPLNIEHRLMLQMAPDYDNLTLIQKVEVFEYALENTPGDDLRRVLWLKSPSSEA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 566 WFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGI 645
Cdd:cd05169   161 WLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLTGKVIHIDFGDCFEVAMHREKFPEKVPFRLTRMLVNAMEVSGV 240

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1778029372 646 DGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWRL 684
Cdd:cd05169   241 EGTFRSTCEDVMRVLRENKDSLMAVLEAFVHDPLISWRL 279
TEL1 super family cl34875
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
8-798 1.39e-170

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: 541.68  E-value: 1.39e-170
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372    8 AFQHLQRFVHTTLHQQALQSLSPTDDDNKR---------EELLKLVARCYLKLGDWMSSLQ-GFNDNTMPQILQYYSAAT 77
Cdd:COG5032   1370 FLRINPELLPLLSSLLNLQSSSLSKQLVSRgssesaisiNSFASVARKHFLPDNQLKKIYQlSNILISEAFLLLRYLLLC 1449

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372   78 DNDRNCYKAWHS-WAFMNFEAVLYYknqQGLEKNGVntaspltpppspkTVNPVISYAVPAVRGFFKSIALSSGNSLQDT 156
Cdd:COG5032   1450 RLGRRELKAGLNvWNLTNLELFSDI---QESEFFEW-------------GKNLKLLSIIPPIEEIFLSNALSCYLQVKDL 1513

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  157 LRLLTLWFDYGHQSEVYESLVEGIKTIQIDT-WLQVIPQLIARIDTPRQLVGRLIHQLLTDIGKHHPQALIYPLTVASKS 235
Cdd:COG5032   1514 LKKLNLFELLGSLLSAKDAAGSYYKNFHIFDlEISVIPFIPQLLSSLSLLDLNSAQSLLSKIGKEHPQALVFTLRSAIES 1593

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  236 ASSARYSAANQILKNMCEHSKQLVQQAIMVSEELIR-VAILWHELWHEGLEEASRLYFGEGN-VKGMFAVLEPLHQMMER 313
Cdd:COG5032   1594 TALSKESVALSLENKSRTHDPSLVKEALELSDENIRiAYPLLHLLFEPILAQLLSRLSSENNkISVALLIDKPLHEEREN 1673

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  314 GPQTLKETSFNQAYGRDLMEAQEWCRRYQKSNNVKDLTQAWDLYYMVFRRISKQLPQLTSLELQYVSPKLLMSRD-LELA 392
Cdd:COG5032   1674 FPSGLSLSSFQSSFLKELIKKSPRKIRKKFKIDISLLNLSRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFHAfLEIK 1753

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  393 VPGTYEPHKPVIHIRHVHSSLNVITS-KQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKR 471
Cdd:COG5032   1754 LPGQYLLDKPFVLIERFEPEVSVVKShLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRR 1833

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  472 HLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRimlrMAPDYDHLTLMEKVEVFEHALANTNgDD 551
Cdd:COG5032   1834 DLWIRPYKVIPLSPGSGIIEWVPNSDTLHSILREYHKRKNISIDQEKK----LAARLDNLKLLLKDEFFTKATLKSP-PV 1908

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  552 LAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFR 631
Cdd:COG5032   1909 LYDWFSESFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGFILFNAPGRFPFPEKVPFR 1988

                          650       660       670       680       690       700       710       720
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  632 LTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWRlmdsaapkikrskgrsdTMSEGAEDMle 711
Cdd:COG5032   1989 LTRNIVEAMGVSGVEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWR-----------------RLPCFREIQ-- 2049

                          730       740       750       760       770       780       790       800
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  712 gvevsrdkptnkkaeplhsiedenahkpealNKKALDIITRVRDKLTGGDFAKRNTLEVPSQVDLLIKQAVSHENLCQCY 791
Cdd:COG5032   2050 -------------------------------NNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQATDPFQLATMY 2098


                   ....*..
gi 1778029372  792 IGWCPFW 798
Cdd:COG5032   2099 IGWMPFW 2105
 
Name Accession Description Interval E-value
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 406-684 0e+00

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: 613.34  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 406 IRHVHSSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLST 485
Cdd:cd05169     1 ISSFDPTLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDERVMQLFGLVNTLLKNDSETSRRNLSIQRYSVIPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 486 NSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMEKVEVFEHALANTNGDDLAKLLWLKSPSSEV 565
Cdd:cd05169    81 NSGLIGWVPGCDTLHSLIRDYREKRKIPLNIEHRLMLQMAPDYDNLTLIQKVEVFEYALENTPGDDLRRVLWLKSPSSEA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 566 WFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGI 645
Cdd:cd05169   161 WLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLTGKVIHIDFGDCFEVAMHREKFPEKVPFRLTRMLVNAMEVSGV 240

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1778029372 646 DGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWRL 684
Cdd:cd05169   241 EGTFRSTCEDVMRVLRENKDSLMAVLEAFVHDPLISWRL 279
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
8-798 1.39e-170

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 541.68  E-value: 1.39e-170
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372    8 AFQHLQRFVHTTLHQQALQSLSPTDDDNKR---------EELLKLVARCYLKLGDWMSSLQ-GFNDNTMPQILQYYSAAT 77
Cdd:COG5032   1370 FLRINPELLPLLSSLLNLQSSSLSKQLVSRgssesaisiNSFASVARKHFLPDNQLKKIYQlSNILISEAFLLLRYLLLC 1449

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372   78 DNDRNCYKAWHS-WAFMNFEAVLYYknqQGLEKNGVntaspltpppspkTVNPVISYAVPAVRGFFKSIALSSGNSLQDT 156
Cdd:COG5032   1450 RLGRRELKAGLNvWNLTNLELFSDI---QESEFFEW-------------GKNLKLLSIIPPIEEIFLSNALSCYLQVKDL 1513

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  157 LRLLTLWFDYGHQSEVYESLVEGIKTIQIDT-WLQVIPQLIARIDTPRQLVGRLIHQLLTDIGKHHPQALIYPLTVASKS 235
Cdd:COG5032   1514 LKKLNLFELLGSLLSAKDAAGSYYKNFHIFDlEISVIPFIPQLLSSLSLLDLNSAQSLLSKIGKEHPQALVFTLRSAIES 1593

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  236 ASSARYSAANQILKNMCEHSKQLVQQAIMVSEELIR-VAILWHELWHEGLEEASRLYFGEGN-VKGMFAVLEPLHQMMER 313
Cdd:COG5032   1594 TALSKESVALSLENKSRTHDPSLVKEALELSDENIRiAYPLLHLLFEPILAQLLSRLSSENNkISVALLIDKPLHEEREN 1673

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  314 GPQTLKETSFNQAYGRDLMEAQEWCRRYQKSNNVKDLTQAWDLYYMVFRRISKQLPQLTSLELQYVSPKLLMSRD-LELA 392
Cdd:COG5032   1674 FPSGLSLSSFQSSFLKELIKKSPRKIRKKFKIDISLLNLSRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFHAfLEIK 1753

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  393 VPGTYEPHKPVIHIRHVHSSLNVITS-KQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKR 471
Cdd:COG5032   1754 LPGQYLLDKPFVLIERFEPEVSVVKShLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRR 1833

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  472 HLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRimlrMAPDYDHLTLMEKVEVFEHALANTNgDD 551
Cdd:COG5032   1834 DLWIRPYKVIPLSPGSGIIEWVPNSDTLHSILREYHKRKNISIDQEKK----LAARLDNLKLLLKDEFFTKATLKSP-PV 1908

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  552 LAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFR 631
Cdd:COG5032   1909 LYDWFSESFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGFILFNAPGRFPFPEKVPFR 1988

                          650       660       670       680       690       700       710       720
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  632 LTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWRlmdsaapkikrskgrsdTMSEGAEDMle 711
Cdd:COG5032   1989 LTRNIVEAMGVSGVEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWR-----------------RLPCFREIQ-- 2049

                          730       740       750       760       770       780       790       800
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  712 gvevsrdkptnkkaeplhsiedenahkpealNKKALDIITRVRDKLTGGDFAKRNTLEVPSQVDLLIKQAVSHENLCQCY 791
Cdd:COG5032   2050 -------------------------------NNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQATDPFQLATMY 2098


                   ....*..
gi 1778029372  792 IGWCPFW 798
Cdd:COG5032   2099 IGWMPFW 2105
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 437-684 8.06e-97

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: 301.17  E-value: 8.06e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 437 FLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRhlsIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKkILLNI 516
Cdd:pfam00454   4 GIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGENG-VPPTA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 517 EHRIMlRMAPDYDHLTLMekvevFEHALANTNGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSN 596
Cdd:pfam00454  80 MVKIL-HSALNYPKLKLE-----FESRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDN 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 597 LMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFVY 676
Cdd:pfam00454 154 ILVDKTTGKLFHIDFGLCLPDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVA 233


                  ....*...
gi 1778029372 677 DPLLNWRL 684
Cdd:pfam00454 234 DGLPDWSI 241
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 437-686 1.19e-93

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: 292.67  E-value: 1.19e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  437 FLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKIllni 516
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGK---- 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  517 ehrimlRMAPDYDHLTLMEKVEVFEHALANTNGDDLAKLLWLKSPS-SEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPS 595
Cdd:smart00146  77 ------VLDLRSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDpSEDYFEARKNFTRSCAGYSVITYILGLGDRHND 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  596 NLMLDRlSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFV 675
Cdd:smart00146 151 NIMLDK-TGHLFHIDFGFILGNGPKLFGFPERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELML 229

                          250
                   ....*....|.
gi 1778029372  676 YDPLLNWRLMD 686
Cdd:smart00146 230 YDGLPDWRSGK 240
FRB_dom pfam08771
FKBP12-rapamycin binding domain; The macrolide antibiotic rapamycin and the cytosol protein ...
 268-365 9.00e-59

FKBP12-rapamycin binding domain; The macrolide antibiotic rapamycin and the cytosol protein FKBP12 can form a complex which specifically inhibits the TORC1 complex, leading to growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FKBP12-rapamycin binding domain (FRB) of the TOR proteins. This entry represents the FRB domain.


Pssm-ID: 462596  Cd Length: 98  Bit Score: 194.34  E-value: 9.00e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 268 ELIRVAILWHELWHEGLEEASRLYFGEGNVKGMFAVLEPLHQMMERGPQTLKETSFNQAYGRDLMEAQEWCRRYQKSNNV 347
Cdd:pfam08771   1 ELIRVAILWHELWYEGLEEASRLYFGEKNIEGMLKILEPLHEMLEKGPETLREISFAQAFGRDLQEAREWLKRYRKTGDE 80

                          90
                  ....*....|....*...
gi 1778029372 348 KDLTQAWDLYYMVFRRIS 365
Cdd:pfam08771  81 EDLNQAWDIYYSVFRRIK 98
 
Name Accession Description Interval E-value
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 406-684 0e+00

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: 613.34  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 406 IRHVHSSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLST 485
Cdd:cd05169     1 ISSFDPTLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDERVMQLFGLVNTLLKNDSETSRRNLSIQRYSVIPLSP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 486 NSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMEKVEVFEHALANTNGDDLAKLLWLKSPSSEV 565
Cdd:cd05169    81 NSGLIGWVPGCDTLHSLIRDYREKRKIPLNIEHRLMLQMAPDYDNLTLIQKVEVFEYALENTPGDDLRRVLWLKSPSSEA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 566 WFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGI 645
Cdd:cd05169   161 WLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLTGKVIHIDFGDCFEVAMHREKFPEKVPFRLTRMLVNAMEVSGV 240

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1778029372 646 DGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWRL 684
Cdd:cd05169   241 EGTFRSTCEDVMRVLRENKDSLMAVLEAFVHDPLISWRL 279
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
8-798 1.39e-170

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 541.68  E-value: 1.39e-170
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372    8 AFQHLQRFVHTTLHQQALQSLSPTDDDNKR---------EELLKLVARCYLKLGDWMSSLQ-GFNDNTMPQILQYYSAAT 77
Cdd:COG5032   1370 FLRINPELLPLLSSLLNLQSSSLSKQLVSRgssesaisiNSFASVARKHFLPDNQLKKIYQlSNILISEAFLLLRYLLLC 1449

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372   78 DNDRNCYKAWHS-WAFMNFEAVLYYknqQGLEKNGVntaspltpppspkTVNPVISYAVPAVRGFFKSIALSSGNSLQDT 156
Cdd:COG5032   1450 RLGRRELKAGLNvWNLTNLELFSDI---QESEFFEW-------------GKNLKLLSIIPPIEEIFLSNALSCYLQVKDL 1513

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  157 LRLLTLWFDYGHQSEVYESLVEGIKTIQIDT-WLQVIPQLIARIDTPRQLVGRLIHQLLTDIGKHHPQALIYPLTVASKS 235
Cdd:COG5032   1514 LKKLNLFELLGSLLSAKDAAGSYYKNFHIFDlEISVIPFIPQLLSSLSLLDLNSAQSLLSKIGKEHPQALVFTLRSAIES 1593

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  236 ASSARYSAANQILKNMCEHSKQLVQQAIMVSEELIR-VAILWHELWHEGLEEASRLYFGEGN-VKGMFAVLEPLHQMMER 313
Cdd:COG5032   1594 TALSKESVALSLENKSRTHDPSLVKEALELSDENIRiAYPLLHLLFEPILAQLLSRLSSENNkISVALLIDKPLHEEREN 1673

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  314 GPQTLKETSFNQAYGRDLMEAQEWCRRYQKSNNVKDLTQAWDLYYMVFRRISKQLPQLTSLELQYVSPKLLMSRD-LELA 392
Cdd:COG5032   1674 FPSGLSLSSFQSSFLKELIKKSPRKIRKKFKIDISLLNLSRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFHAfLEIK 1753

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  393 VPGTYEPHKPVIHIRHVHSSLNVITS-KQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKR 471
Cdd:COG5032   1754 LPGQYLLDKPFVLIERFEPEVSVVKShLQRPRRLTIRGSDGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRR 1833

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  472 HLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRimlrMAPDYDHLTLMEKVEVFEHALANTNgDD 551
Cdd:COG5032   1834 DLWIRPYKVIPLSPGSGIIEWVPNSDTLHSILREYHKRKNISIDQEKK----LAARLDNLKLLLKDEFFTKATLKSP-PV 1908

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  552 LAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFR 631
Cdd:COG5032   1909 LYDWFSESFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRSSGHVIHIDFGFILFNAPGRFPFPEKVPFR 1988

                          650       660       670       680       690       700       710       720
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  632 LTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWRlmdsaapkikrskgrsdTMSEGAEDMle 711
Cdd:COG5032   1989 LTRNIVEAMGVSGVEGSFRELCETAFRALRKNADSLMNVLELFVRDPLIEWR-----------------RLPCFREIQ-- 2049

                          730       740       750       760       770       780       790       800
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  712 gvevsrdkptnkkaeplhsiedenahkpealNKKALDIITRVRDKLTGGDFAKRNTLEVPSQVDLLIKQAVSHENLCQCY 791
Cdd:COG5032   2050 -------------------------------NNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQATDPFQLATMY 2098


                   ....*..
gi 1778029372  792 IGWCPFW 798
Cdd:COG5032   2099 IGWMPFW 2105
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 437-684 8.06e-97

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: 301.17  E-value: 8.06e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 437 FLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRhlsIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKkILLNI 516
Cdd:pfam00454   4 GIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRR---LKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGENG-VPPTA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 517 EHRIMlRMAPDYDHLTLMekvevFEHALANTNGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSN 596
Cdd:pfam00454  80 MVKIL-HSALNYPKLKLE-----FESRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDN 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 597 LMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFVY 676
Cdd:pfam00454 154 ILVDKTTGKLFHIDFGLCLPDAGKDLPFPEKVPFRLTREMVYAMGPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVA 233


                  ....*...
gi 1778029372 677 DPLLNWRL 684
Cdd:pfam00454 234 DGLPDWSI 241
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 412-677 1.12e-96

Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members include ATM (Ataxia telangiectasia mutated), ATR (Ataxia telangiectasia and Rad3-related), TOR (Target of rapamycin), SMG-1 (Suppressor of morphogenetic effect on genitalia-1), and DNA-PK (DNA-dependent protein kinase). PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). They show strong preference for phosphorylating serine/threonine residues followed by a glutamine and are also referred to as (S/T)-Q-directed kinases. They all contain a FATC (FRAP, ATM and TRRAP, C-terminal) domain. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PIKK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 299.96  E-value: 1.12e-96
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 412 SLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLSTNSGLIG 491
Cdd:cd05164     7 RVRILASLQKPKKITILGSDGKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKETRKRNLTIRTYSVVPLSSQSGLIE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 492 WVPHCDTLHalirdyrekkkillniehrimlrmapdydhltlmekvevfehalantngDDLAKLLWLKSPSSEVWFDRRT 571
Cdd:cd05164    87 WVDNTTTLK-------------------------------------------------PVLKKWFNETFPDPTQWYEARS 117

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 572 NYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKfPEKIPFRLTRMLTNAMEVTGIDGNYRM 651
Cdd:cd05164   118 NYTKSTAVMSMVGYIIGLGDRHLENILIDTKTGEVVHIDFGMIFNKGKTLPV-PEIVPFRLTRNIINGMGPTGVEGLFRK 196

                         250       260
                  ....*....|....*....|....*.
gi 1778029372 652 TCESVMRTLREHKDSLMAVLEAFVYD 677
Cdd:cd05164   197 SCEQVLRVFRKHKDKLITFLDTFLYD 222
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 437-686 1.19e-93

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: 292.67  E-value: 1.19e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  437 FLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKIllni 516
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYRKQKGK---- 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  517 ehrimlRMAPDYDHLTLMEKVEVFEHALANTNGDDLAKLLWLKSPS-SEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPS 595
Cdd:smart00146  77 ------VLDLRSQTATRLKKLELFLEATGKFPDPVLYDWFTKKFPDpSEDYFEARKNFTRSCAGYSVITYILGLGDRHND 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372  596 NLMLDRlSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFV 675
Cdd:smart00146 151 NIMLDK-TGHLFHIDFGFILGNGPKLFGFPERVPFRLTPEMVDVMGDSGYFGLFRSLCERALRALRKNSNLIMSLLELML 229

                          250
                   ....*....|.
gi 1778029372  676 YDPLLNWRLMD 686
Cdd:smart00146 230 YDGLPDWRSGK 240
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 406-682 2.42e-87

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: 278.75  E-value: 2.42e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 406 IRHVHSSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLST 485
Cdd:cd05170     1 IQSVGSTVTVLPTKTKPKKLVFLGSDGKRYPYLFKGLEDLHLDERIMQFLSIVNAMLASDNEHRRRRYRARHYSVTPLGP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 486 NSGLIGWVPHCDTLHALIRDYREKKKILLNIE--------HRIMLRMAPDYDHLT--LMEKV----------------EV 539
Cdd:cd05170    81 RSGLIQWVDGATPLFSLYKRWQQRRAAAQAQKnqdsgstpPPVPRPSELFYNKLKpaLKAAGirkstsrrewplevlrQV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 540 FEHALANTNGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAm 619
Cdd:cd05170   161 LEELVAETPRDLLARELWCSSPSSAEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDLSTGEVVHIDYNVCFEKG- 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1778029372 620 TREKFPEKIPFRLTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNW 682
Cdd:cd05170   240 KRLRVPEKVPFRLTQNIEHALGPTGVEGTFRLSCEQVLKILRKGRETLLTLLEAFVYDPLVDW 302
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 406-683 2.69e-86

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: 273.23  E-value: 2.69e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 406 IRHVHSSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLST 485
Cdd:cd00892     1 ISGFEDEVEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 486 NSGLIGWVPHCDTLHALIRDYRekKKILlnieHRIMLRMAPDydhltlmekvevfehalantngddlakllwlksPSSev 565
Cdd:cd00892    81 ECGIIEWVPNTVTLRSILSTLY--PPVL----HEWFLKNFPD---------------------------------PTA-- 119

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 566 WFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFgDC-FEVAMTREKfPEKIPFRLTRMLTNAMEVTG 644
Cdd:cd00892   120 WYEARNNYTRSTAVMSMVGYILGLGDRHGENILFDSTTGDVVHVDF-DClFDKGLTLEV-PERVPFRLTQNMVDAMGVTG 197

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1778029372 645 IDGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWR 683
Cdd:cd00892   198 VEGTFRRTCEVTLRVLRENRETLMSVLETFVHDPLVEWS 236
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 406-684 2.49e-84

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: 269.79  E-value: 2.49e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 406 IRHVHSSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDeRVM-QLFGLVNTLLSSDRATSKRHLSIQRYAVIPLS 484
Cdd:cd05171     1 ISRFEDTFTLAGGINLPKIITCIGSDGKKYKQLVKGGDDLRQD-AVMeQVFELVNQLLKRDKETRKRKLRIRTYKVVPLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 485 TNSGLIGWVPHCDTLHALIRDY--------REKKKILLNIEHRIMLRMAPDYDhltLMEKVEVFEHALANTngddlaK-- 554
Cdd:cd05171    80 PRSGVLEFVENTIPLGEYLVGAssksgahaRYRPKDWTASTCRKKMREKAKAS---AEERLKVFDEICKNF------Kpv 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 555 ---LLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAmTREKFPEKIPFR 631
Cdd:cd05171   151 frhFFLEKFPDPSDWFERRLAYTRSVATSSIVGYILGLGDRHLNNILIDQKTGELVHIDLGIAFEQG-KLLPIPETVPFR 229

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1778029372 632 LTRMLTNAMEVTGIDGNYRMTCESVMRTLREHKDSLMAVLEAFVYDPLLNWRL 684
Cdd:cd05171   230 LTRDIVDGMGITGVEGVFRRCCEETLRVLRENKEALLTILEVLLYDPLYSWTV 282
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 411-677 2.48e-76

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: 246.09  E-value: 2.48e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 411 SSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRatskRHLSIQRYAVIPLSTNSGLI 490
Cdd:cd00142     6 GILKVIHSKQRPKKITLIGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKES----VNLVLPPYKVIPLSENSGLI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 491 GWVPHCDTLHalirdyrekkkillniehrimlrmapdydhltlmekvevfehalantngdDLAKLLWLKSPSSEVWFDRR 570
Cdd:cd00142    82 EIVKDAQTIE--------------------------------------------------DLLKSLWRKSPSSQSWLNRR 111

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 571 TNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRlSGRILHIDFGDCFEVAMTREKFpEKIPFRLTRMLTNAMEVTGIDGNYR 650
Cdd:cd00142   112 ENFSCSLAGYSVLGYIFGIGDRHPSNIMIEP-SGNIFHIDFGFIFSGRKLAEGV-ETVPFRLTPMLENAMGTAGVNGPFQ 189

                         250       260
                  ....*....|....*....|....*..
gi 1778029372 651 MTCESVMRTLREHKDSLMAVLEAFVYD 677
Cdd:cd00142   190 ISMVKIMEILREHADLIVPILEHSLRD 216
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 411-683 1.36e-69

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: 229.00  E-value: 1.36e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 411 SSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLSTNSGLI 490
Cdd:cd05172     6 PRVLVLSSKRRPKRITIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDPACRQRRLRIRTYQVIPMTSRLGLI 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 491 GWVPHCDTLHALIRDYrekkkillniehriMLRMApdydhltlmekvevfehalantngddlaklLWLKSPSSEVWFDRR 570
Cdd:cd05172    86 EWVDNTTPLKEILEND--------------LLRRA------------------------------LLSLASSPEAFLALR 121

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 571 TNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGIDGNYR 650
Cdd:cd05172   122 SNFARSLAAMSICGYILGIGDRHLSNFLVDLSTGRLIGIDFGHAFGSATQFLPIPELVPFRLTRQLLNLLQPLDARGLLR 201

                         250       260       270
                  ....*....|....*....|....*....|...
gi 1778029372 651 MTCESVMRTLREHKDSLMAVLEAFVYDPLLNWR 683
Cdd:cd05172   202 SDMVHVLRALRAGRDLLLATMDVFVKEPLLDWQ 234
FRB_dom pfam08771
FKBP12-rapamycin binding domain; The macrolide antibiotic rapamycin and the cytosol protein ...
 268-365 9.00e-59

FKBP12-rapamycin binding domain; The macrolide antibiotic rapamycin and the cytosol protein FKBP12 can form a complex which specifically inhibits the TORC1 complex, leading to growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FKBP12-rapamycin binding domain (FRB) of the TOR proteins. This entry represents the FRB domain.


Pssm-ID: 462596  Cd Length: 98  Bit Score: 194.34  E-value: 9.00e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 268 ELIRVAILWHELWHEGLEEASRLYFGEGNVKGMFAVLEPLHQMMERGPQTLKETSFNQAYGRDLMEAQEWCRRYQKSNNV 347
Cdd:pfam08771   1 ELIRVAILWHELWYEGLEEASRLYFGEKNIEGMLKILEPLHEMLEKGPETLREISFAQAFGRDLQEAREWLKRYRKTGDE 80

                          90
                  ....*....|....*...
gi 1778029372 348 KDLTQAWDLYYMVFRRIS 365
Cdd:pfam08771  81 EDLNQAWDIYYSVFRRIK 98
FAT pfam02259
FAT domain; The FAT domain is named after FRAP, ATM and TRRAP.
 5-161 1.52e-36

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


Pssm-ID: 396714 [Multi-domain]  Cd Length: 342  Bit Score: 140.95  E-value: 1.52e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372   5 QEDAFQHLQRFVHTTLHQQ-ALQSLSPTDDDNKREELLKLVARCYLKLGDWMSSLQGFNDNTMPQ-ILQYYSAATDNDRN 82
Cdd:pfam02259 201 QQEALLKLREFLSCYLQKNgELLSGLEVINPTNLEEFTELLARCYLLKGKWQAALGQNWAEEKSEeILQAYLLATQFDPS 280

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1778029372  83 CYKAWHSWAFMNFEAVLYYKNQQglekngvntaspltpppSPKTVNPVISYAVPAVRGFFKSIALSSGNSLQDTLRLLT 161
Cdd:pfam02259 281 WYKAWHTWALFNFEVLRKEEQGK-----------------EEEGPEDLSRYVVPAVEGYLRSLSLSSENSLQDTLRLLT 342
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 399-669 6.13e-27

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: 113.01  E-value: 6.13e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 399 PHKPVIHIrhVHSSLNVITSKQRPRKLCITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLssdratsKRH---LSI 475
Cdd:cd00896    59 PSVKVTGI--IPEKSTVFKSALMPLKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLL-------KKEnldLKL 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 476 QRYAVIPLSTNSGLIGWVPHCDTLHALIRDYrekKKILlniehrimlrmapDYdhltlmekvevfehaLANTNGDDLAKL 555
Cdd:cd00896   130 TPYKVLATSPNDGLVEFVPNSKALADILKKY---GSIL-------------NF---------------LRKHNPDESGPY 178

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 556 LwlkspsseVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRlSGRILHIDFG-----DCfevamtreK-FPEkiP 629
Cdd:cd00896   179 G--------IKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTK-DGHLFHIDFGyilgrDP--------KpFPP--P 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1778029372 630 FRLTRMLTNAMEVTGIDG--NYRMTCESVMRTLREHKD------SLMA 669
Cdd:cd00896   240 MKLCKEMVEAMGGANSEGykEFKKYCCTAYNILRKHANlilnlfSLMV 287
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 423-682 1.71e-25

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: 106.07  E-value: 1.71e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 423 RKLCITGSNGSEFMFLLK--GHEDLRQDERVMQLFGLVNTLLSSDRATSKRHLSIQRYAVIPLSTNsgligwvphcdtlh 500
Cdd:cd05163    19 RRLTIRGHDGSKYPFLVQtpSARHSRREERVMQLFRLLNRVLERKKETRRRNLQFHVPIVVPLSPQ-------------- 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 501 alirdyrekkkillniehrimLR-MAPDYDHLTLM---EKVEVFEHALANTNGDDLAKLLWLKS-PS-SEVWFDRRTnYT 574
Cdd:cd05163    85 ---------------------VRlVEDDPSYISLQdiyEKLEILNEIQSKMVPETILSNYFLRTmPSpSDLWLFRKQ-FT 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 575 RSLAVMSMVGYVLGLGDRHPSNLMLDRLSGRILHIDFgdCFEVAMTR--EKFPEKIPFRLTRMLTNAMEVTGIDGNYRMT 652
Cdd:cd05163   143 LQLALSSFMTYVLSLGNRTPHRILISRSTGNVFMTDF--LPSINSQGplLDNNEPVPFRLTPNIQHFIGPIGVEGLLTSS 220

                         250       260       270
                  ....*....|....*....|....*....|
gi 1778029372 653 CESVMRTLREHKDSLMAVLEAFVYDPLLNW 682
Cdd:cd05163   221 MMAIARALTEPEYDLEQYLSLFVRDELISW 250
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 415-663 3.81e-19

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: 89.55  E-value: 3.81e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 415 VITSKQRPRKLCITGS--NGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLssdratsKRH---LSIQRYAVIPLSTNSGL 489
Cdd:cd00891    66 VMDSKKLPLWLVFKNAdpGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLW-------KKEgldLRMTPYKCIATGDEVGM 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 490 IGWVPHCDTLHALIRDYREKKKillniehrimlrmapdydhltlmekveVF-EHALANtngddlakllWLKS--PSSEVW 566
Cdd:cd00891   139 IEVVPNSETTAAIQKKYGGFGA---------------------------AFkDTPISN----------WLKKhnPTEEEY 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 567 FDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRlSGRILHIDFG---DCFevamtREKF---PEKIPFRLTRMLTNAM 640
Cdd:cd00891   182 EEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTK-SGHLFHIDFGhflGNF-----KKKFgikRERAPFVFTPEMAYVM 255

                         250       260
                  ....*....|....*....|....*..
gi 1778029372 641 evTGIDG-NYRMTCESVMRT---LREH 663
Cdd:cd00891   256 --GGEDSeNFQKFEDLCCKAyniLRKH 280
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 415-672 5.65e-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: 77.33  E-value: 5.65e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 415 VITSKQRPRKLCITGSN--GSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSDRAtskrHLSIQRYAVIPLSTNSGLIGW 492
Cdd:cd05166    69 YFNSNALPLKLVFRNADprAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGL----DLKMITFRCVPTGNKRGMVEL 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 493 VPHCDTLhalirdyREKKKillniehrimlrmapdydhltlmekvevfEHALANTNGDD-LAKLLWLKSPSSEVWFDRRT 571
Cdd:cd05166   145 VPEAETL-------REIQT-----------------------------EHGLTGSFKDRpLADWLQKHNPSELEYEKAVE 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 572 NYTRSLAVMSMVGYVLGLGDRHPSNLMLDRlSGRILHIDFGDCFEVAMTREKFP-EKIPFrltrMLTNAMeVTGIDGNYR 650
Cdd:cd05166   189 NFIRSCAGYCVATYVLGICDRHNDNIMLKT-SGHLFHIDFGKFLGDAQMFGNFKrDRVPF----VLTSDM-AYVINGGDK 262

                         250       260       270
                  ....*....|....*....|....*....|.
gi 1778029372 651 MT---------CESVMRTLREHKDSLMAVLE 672
Cdd:cd05166   263 PSsrfqlfvdlCCQAFNIIRKNSNLLLNLLS 293
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 437-672 1.95e-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: 74.83  E-value: 1.95e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 437 FLLKGHEDLRQDERVMQLFGLVNTLLSSDRATskrhLSIQRYAVIPLSTNSGLIGWVPhcDT--LHALirdyreKKKill 514
Cdd:cd05168    33 VIVKSGDDLRQELLAMQLIKQFQRIFEEAGLP----LWLRPYEILVTSSDSGLIETIP--DTvsIDSL------KKR--- 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 515 niehrimlrmAPDYDHLTlmekvEVFEhalaNTNGDdlakllwlksPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHP 594
Cdd:cd05168    98 ----------FPNFTSLL-----DYFE----RTFGD----------PNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHN 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 595 SNLMLDRlSGRILHIDFGDCFEVAMTREKFpEKIPFRLTRMLTNAMEvtGIDGN----YRMTCESVMRTLREHKDSLMAV 670
Cdd:cd05168   149 GNILLDS-EGHIIHIDFGFMLSNSPGGLGF-ETAPFKLTQEYVEVMG--GLESDmfryFKTLMIQGFLALRKHADRIVLL 224


                  ..
gi 1778029372 671 LE 672
Cdd:cd05168   225 VE 226
FATC pfam02260
FATC domain; The FATC domain is named after FRAP, ATM, TRRAP C-terminal. The solution ...
 767-798 3.58e-14

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: 66.64  E-value: 3.58e-14
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1778029372 767 TLEVPSQVDLLIKQAVSHENLCQCYIGWCPFW 798
Cdd:pfam02260   1 PLSVEGQVDELIQEATDPENLAQMYIGWCPWW 32
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 428-663 3.76e-14

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: 74.70  E-value: 3.76e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 428 TGSNGSEFMFllKGHEDLRQDERVMQLFGLVNTLLSsdraTSKRHLSIQRYAVIPLSTNSGLIGWVPHCDTLhalirdyr 507
Cdd:cd05174    93 AGAGNVGIIF--KNGDDLRQDMLTLQMIQLMDVLWK----QEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI-------- 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 508 ekKKILLNIEHrimlrMApdydhltlmekvevfehALANTNGDDLakLLWLKSPSSEVWFDRRTN-YTRSLAVMSMVGYV 586
Cdd:cd05174   159 --ANIQLNKSN-----MA-----------------ATAAFNKDAL--LNWLKSKNPGDALDQAIEeFTLSCAGYCVATYV 212

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 587 LGLGDRHPSNLMLdRLSGRILHIDFGDCfeVAMTREKF---PEKIPFRLTRMLTNAMEvTGIDGN------YRMTCESVM 657
Cdd:cd05174   213 LGIGDRHSDNIMI-RESGQLFHIDFGHF--LGNFKTKFginRERVPFILTYDFVHVIQ-QGKTNNsekferFRGYCERAY 288


                  ....*.
gi 1778029372 658 RTLREH 663
Cdd:cd05174   289 TILRRH 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 437-674 6.83e-14

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


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 73.06  E-value: 6.83e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 437 FLLKGHEDLRQDERVMQLFGLVNTLLssdrATSKRHLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILlni 516
Cdd:cd00893    30 LIVKTGDDLKQEQLALQLISQFDQIF----KEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKLDSFNKFV--- 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 517 ehrimlrmapdydhlTLMEkveVFEHALANTNGDDLakllwlkspssevwfdrRTNYTRSLAVMSMVGYVLGLGDRHPSN 596
Cdd:cd00893   103 ---------------SLSD---FFDDNFGDEAIQKA-----------------RDNFLQSLVAYSLVCYFLQIKDRHNGN 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 597 LMLDRlSGRILHIDFGDCFEVAMTREKFpEKIPFRLTRMLTNAMEvtGIDGN----YRMTCESVMRTLREHKDSLMAVLE 672
Cdd:cd00893   148 ILLDK-EGHIIHIDFGFFLSSHPGFYGF-EGAPFKLSSEYIEVLG--GVDSElfkeFRKLFLKGFMALRKHSDKILSLVE 223


                  ..
gi 1778029372 673 AF 674
Cdd:cd00893   224 MM 225
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 415-633 3.44e-13

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: 71.90  E-value: 3.44e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 415 VITSKQRPRKLC-----ITGSNGSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSD----RATSkrhlsiqrYAVIPLST 485
Cdd:cd05165    71 VMDSKKRPLWLVfenadPLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEgldlRMLP--------YGCLSTGD 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 486 NSGLIGWVPHCDTLhalirdyrekkkilLNIEHRIMLRmapdydhltlmekvevfehALANTNGDDLAKllWLK--SPSS 563
Cdd:cd05165   143 NVGLIEVVRNAKTI--------------ANIQKKKGKV-------------------ATLAFNKDSLHK--WLKekNKTG 187

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1778029372 564 EVwFDRR-TNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRlSGRILHIDFG---DCFevamtREKF---PEKIPFRLT 633
Cdd:cd05165   188 EK-YDRAiEEFTLSCAGYCVATYVLGIGDRHSDNIMVKE-NGQLFHIDFGhflGNF-----KKKFgikRERVPFVLT 257
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 440-676 1.54e-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: 69.16  E-value: 1.54e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 440 KGHEDLRQDE---RVMQLFGLVNTLLSSDratskrhLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYRekkkillni 516
Cdd:cd05167    55 KVGDDCRQDMlalQLISLFKNIFEEVGLD-------LYLFPYRVVATGPGCGVIEVIPNSKSRDQIGRETD--------- 118

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 517 ehrimlrmapdydhltlMEKVEVFEHalanTNGDdlakllwlksPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSN 596
Cdd:cd05167   119 -----------------NGLYEYFLS----KYGD----------ESTPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGN 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 597 LMLDRlSGRILHIDFGDCFEVA----MtreKFpEKIPFRLTRMLTNAMEVTGIDGNYRMTCESVMR---TLREHKDSLMA 669
Cdd:cd05167   168 IMIDD-DGHIIHIDFGFIFEISpggnL---GF-ESAPFKLTKEMVDLMGGSMESEPFKWFVELCVRgylAVRPYAEAIVS 242


                  ....*..
gi 1778029372 670 VLEAFVY 676
Cdd:cd05167   243 LVELMLD 249
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 399-663 2.83e-11

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: 66.14  E-value: 2.83e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 399 PHKPVIHIRHVH-SSLNVITSKQRPrkLCITGSN----GSEFMFLLKGHEDLRQDERVMQLFGLVNTLLSSdratSKRHL 473
Cdd:cd05173    56 PLNPSIILSELNvEKCKYMDSKMKP--LWIVYNNklfgGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKE----AGLDL 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 474 SIQRYAVIPLSTNSGLIGWVPHCDTLhalirdyrekKKILLNIEHrimlrMApdydhltlmekvevfehALANTNGDDLa 553
Cdd:cd05173   130 RIVPYGCLATGDRSGLIEVVSSAETI----------ADIQLNSSN-----VA-----------------AAAAFNKDAL- 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 554 kLLWLKSPSSEVWFDRRTN-YTRSLAVMSMVGYVLGLGDRHPSNLMLdRLSGRILHIDFGDCfeVAMTREKFP---EKIP 629
Cdd:cd05173   177 -LNWLKEYNSGDDLERAIEeFTLSCAGYCVATYVLGIGDRHSDNIMV-RKNGQLFHIDFGHI--LGNFKSKFGikrERVP 252

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1778029372 630 FRLTRMLTNAMEvTGIDGN------YRMTCESVMRTLREH 663
Cdd:cd05173   253 FILTYDFIHVIQ-QGKTGNtekfgrFRQYCEDAYLILRKN 291
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 417-633 2.27e-08

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: 56.91  E-value: 2.27e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 417 TSKQRPRKLCITGSN--GSEFMFLLKGHEDLRQDERVMQLFGLVntllssDRATSKRHLSIQRYAVIPLST--NSGLIGW 492
Cdd:cd05176    71 SSNAVPLKVALVNADplGEEINVMFKVGEDLRQDMLALQMIKIM------DKIWLQEGLDLRMVIFKCLSTgkDRGMVEL 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 493 VPHCDTLhalirdyrekkkillniehrimlrmapdydhltlmEKVEVfEHALANTNGDD-LAKLLWLKSPSSEVWFDRRT 571
Cdd:cd05176   145 VPSSDTL-----------------------------------RKIQV-EYGVTGSFKDKpLAEWLRKYNPSEEEYEKASE 188

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1778029372 572 NYTRSLAVMSMVGYVLGLGDRHPSNLMLdRLSGRILHIDFGDCFEVAMTREKFP-EKIPFRLT 633
Cdd:cd05176   189 NFIYSCAGCCVATYVLGICDRHNDNIML-RSTGHMFHIDFGKFLGHAQMFGSFKrDRAPFVLT 250
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 368-634 5.09e-06

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: 49.67  E-value: 5.09e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 368 LPQLTSLELQYVSPKLLMSR----DLELAVPGTYEPHKPVIHIRHVH-SSLNVITSKQRPRKLCITGSN-GSEFMF---- 437
Cdd:cd05175    25 LKQEKKDETQKVQMKFLVEQmrrpDFMDALQGFLSPLNPAHQLGNLRlEECRIMSSAKRPLWLNWENPDiMSELLFqnne 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 438 -LLKGHEDLRQDERVMQLFGLVNTLLSSdratSKRHLSIQRYAVIPLSTNSGLIGWVPHCDTLhalirdyrekkkilLNI 516
Cdd:cd05175   105 iIFKNGDDLRQDMLTLQIIRIMENIWQN----QGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI--------------MQI 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 517 EHRIMLRMAPDYDHLTLMEkvevfehalantngddlakllWLKSPSSEVWFDRRTN-YTRSLAVMSMVGYVLGLGDRHPS 595
Cdd:cd05175   167 QCKGGLKGALQFNSHTLHQ---------------------WLKDKNKGEIYDAAIDlFTRSCAGYCVATFILGIGDRHNS 225

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1778029372 596 NLMLdRLSGRILHIDFGDCFEvaMTREKF---PEKIPFRLTR 634
Cdd:cd05175   226 NIMV-KDDGQLFHIDFGHFLD--HKKKKFgykRERVPFVLTQ 264
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 519-612 2.58e-05

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 47.30  E-value: 2.58e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 519 RIMLRMAPDYDHLtlmEKVEVfEHALANTNGD-DLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNL 597
Cdd:cd00895   140 RGMVEMIPNAETL---RKIQV-EHGVTGSFKDrPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNI 215

                          90
                  ....*....|....*
gi 1778029372 598 MLdRLSGRILHIDFG 612
Cdd:cd00895   216 ML-KTTGHMFHIDFG 229
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 557-668 7.96e-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: 45.62  E-value: 7.96e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 557 WLKS--PSSEVWFDRRTNYTRSLAVMSMVGYVLGLGDRHPSNLMLDRlSGRILHIDFGdcfEVAMTREKF----PEKIPF 630
Cdd:cd00894   182 WLKEkcPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITE-TGNLFHIDFG---HILGNYKSFlginKERVPF 257

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1778029372 631 RLTRMLTNAMEVTGIDGN-----YRMTCESVMRTLREHKDSLM 668
Cdd:cd00894   258 VLTPDFLFVMGTSGKKTSlhfqkFQDVCVKAYLALRHHTNLLI 300
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 399-676 1.86e-04

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


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 44.50  E-value: 1.86e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 399 PHKPVIHIRHV-HSSLNVITSKQRPRKLCITGSN--GSEFMFLLKGHEDLRQDERVMQLFGLVntllssDRATSKRHLSI 475
Cdd:cd05177    53 PLNPALRVKGIdADACSYFTSNAAPLKISFINANplAKNISIIFKTGDDLRQDMLVLQIVRVM------DNIWLQEGLDM 126

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 476 QRYAVIPLST--NSGLIGWVPHCDTLhalirdyrekKKIllnieHRimlrmapdydhltlmekvevfEHALANTngddla 553
Cdd:cd05177   127 QMIIYRCLSTgkTQGLVQMVPDAVTL----------AKI-----HR---------------------ESGLIGP------ 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1778029372 554 kllwLKSPSSEVWFDRRT-----------NYTRSLAVMSMVGYVLGLGDRHPSNLMLDRlSGRILHIDFGDCFEVAMTRE 622
Cdd:cd05177   165 ----LKENTIEKWFHMHNklkedydkavrNFFHSCAGWCVVTFILGVCDRHNDNIMLTH-SGHMFHIDFGKFLGHAQTFG 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1778029372 623 KFP-EKIPFrltrMLTNAMEVTGIDG--------NYRMTCESVMRTLREHKDSLMAVLEAFVY 676
Cdd:cd05177   240 SIKrDRAPF----IFTSEMEYFITEGgkkpqrfqRFVELCCRAYNIVRKHSQLLLNLLEMMLH 298
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH