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Conserved domains on  [gi|1195569754|ref|NP_001338622|]
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pleckstrin homology domain-containing family G member 2 isoform 2 [Homo sapiens]

Protein Classification

pleckstrin homology domain-containing family G protein( domain architecture ID 10457355)

pleckstrin homology (PH) domain-containing family G protein contains PH and RhoGEF domains and may function as a guanine nucleotide exchange factor; similar to Homo sapiens pleckstrin homology domain-containing family G members 1/2/3 (PLEKHG1/2/3) that are involved in the regulation of Rho protein signal transduction

Gene Ontology:  GO:0005085|GO:0051056
PubMed:  11738596

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 204-354 4.96e-61

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 205.28  E-value: 4.96e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  204 REMVEEAIVSMTAVAWYINDMKRKQEHAARLQEVQRRLGGWTGPELSAFGELVLEgafrggGGGGPRLRGGERLLFLFSR 283
Cdd:cd13243      1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLE------GTFRMAGAKNERLLFLFDK 74

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1195569754  284 MLLVAKRR-GLEYTYKGHIFCCNLSVSES-PRDPLGFKVSDLTIPKHRHLLQAKNQEEKRLWIHCLQRLFFEN 354
Cdd:cd13243     75 MLLITKKReDGILQYKTHIMCSNLMLSESiPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 47-222 1.08e-50

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 176.72  E-value: 1.08e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   47 VAREIVETERAYVRDLRSIVEDYLGPLLDggVLGLSVEQVGTLFANIEDIYEFS-SELLEDL-ENSSSAGGIAECFVQRS 124
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSK--PLSESEEEIKTIFSNIEEIYELHrQLLLEELlKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  125 EDFDIYTLYCMNYPSSLALLRELSLSPPA-ALWLQERQAQLR-HSLPLQSFLLKPVQRILKYHLLLQELGKHWAegPGTG 202
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLKKNPKfRAFLEELEANPEcRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP--PDHP 156

                          170       180
                   ....*....|....*....|
gi 1195569754  203 GREMVEEAIVSMTAVAWYIN 222
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 384-845 1.44e-05

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 49.94  E-value: 1.44e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  384 PLTPPLGSPRPRDaRSFTPGRrnTAPSP-GPSVIRRGRRQSEPvkdpyvmfPQNAKPGFKHAGSEGELYPPESQPPVSGS 462
Cdd:PHA03247  2553 PPLPPAAPPAAPD-RSVPPPR--PAPRPsEPAVTSRARRPDAP--------PQSARPRAPVDDRGDPRGPAPPSPLPPDT 2621

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  463 APPEdledagPPTLDPSgtsiteeilellnQRGLRDPGPSTHDIPKFPGDSQVPGDSETltfqALPSRDSSEEEEEEEEG 542
Cdd:PHA03247  2622 HAPD------PPPPSPS-------------PAANEPDPHPPPTVPPPERPRDDPAPGRV----SRPRRARRLGRAAQASS 2678

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  543 lemDERGPSPlhvlegleSSIAAEMPSIPCLTKIPDVPNLPEIPSRCEIPEGSRLPSLSDISDVF-EMPCLPAIPSVPNT 621
Cdd:PHA03247  2679 ---PPQRPRR--------RAARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASpALPAAPAPPAVPAG 2747

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  622 PSLSSTPTLscdswlQGPLQEPAEAPATRRELFSGSNPGKLGEPPSGGKAGPEEDEEGVSFTDFQPQDVTQHQGFPDELA 701
Cdd:PHA03247  2748 PATPGGPAR------PARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPA 2821

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  702 FRSCSEIRSAWQALEQGQLARPGFPEPLLILEDSDL-GGD----SGSGKAGAPSSERTASRVRELARLYSERIQQ----- 771
Cdd:PHA03247  2822 ASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVApGGDvrrrPPSRSPAAKPAAPARPPVRRLARPAVSRSTEsfalp 2901

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1195569754  772 ---MQRAETRASANAPRRRPRVLAQPQPSPCLPQE-QAEPGLLPAFGHvlvcelafplTCAQESVPLGPAVWVQAAIP 845
Cdd:PHA03247  2902 pdqPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPpRPQPPLAPTTDP----------AGAGEPSGAVPQPWLGALVP 2969
Atrophin-1 super family cl38111
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 710-1094 1.99e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


The actual alignment was detected with superfamily member pfam03154:

Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 42.45  E-value: 1.99e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  710 SAWQALEQGQLARPGFPEPLLILEDSDLGGDSGSGKAGAPSSERTASRVRELARLYSERIQQMQRAETRASANAPRRRPR 789
Cdd:pfam03154  161 SAQQQILQTQPPVLQAQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQSTAAPHTLIQQTPTLHPQ 240

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  790 VLA------QPQPSPCLPQEQAEPGLLPAFGHVLVCELAFPLTCaqesvplGPAVwVQAAIPLSKQGGSPDGQGLHVSNL 863
Cdd:pfam03154  241 RLPsphpplQPMTQPPPPSQVSPQPLPQPSLHGQMPPMPHSLQT-------GPSH-MQHPVPPQPFPLTPQSSQSQVPPG 312

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  864 PKQDLPGIHVSAATLLPEQGGSRHVQAPAATPLPKQEGPLhlqvpalttfsdqghPEIQVPATTPLPEhrshmvIPAPST 943
Cdd:pfam03154  313 PSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSM---------------PHIKPPPTTPIPQ------LPNPQS 371

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  944 afcpeQGHCADIHVPTTPALPKEICSDFTVSVTTPVPKQegHLDSESPTNIPLTKQggSRDVQGP---DPVCSQPiQPLS 1020
Cdd:pfam03154  372 -----HKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTH--HPPSAHPPPLQLMPQ--SQQLPPPpaqPPVLTQS-QSLP 441

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1195569754 1021 WHGSSLDPQGPGDTLPPLPCHLPDLQIPGTSP--LPAHGshldhrIPANAPLSLSQELPDTQVPATTPLPLPQVLT 1094
Cdd:pfam03154  442 PPAASHPPTSGLHQVPSQSPFPQHPFVPGGPPpiTPPSG------PPTSTSSAMPGIQPPSSASVSSSGPVPAAVS 511
 
Name Accession Description Interval E-value
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 204-354 4.96e-61

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 205.28  E-value: 4.96e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  204 REMVEEAIVSMTAVAWYINDMKRKQEHAARLQEVQRRLGGWTGPELSAFGELVLEgafrggGGGGPRLRGGERLLFLFSR 283
Cdd:cd13243      1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLE------GTFRMAGAKNERLLFLFDK 74

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1195569754  284 MLLVAKRR-GLEYTYKGHIFCCNLSVSES-PRDPLGFKVSDLTIPKHRHLLQAKNQEEKRLWIHCLQRLFFEN 354
Cdd:cd13243     75 MLLITKKReDGILQYKTHIMCSNLMLSESiPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 47-222 1.08e-50

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 176.72  E-value: 1.08e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   47 VAREIVETERAYVRDLRSIVEDYLGPLLDggVLGLSVEQVGTLFANIEDIYEFS-SELLEDL-ENSSSAGGIAECFVQRS 124
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSK--PLSESEEEIKTIFSNIEEIYELHrQLLLEELlKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  125 EDFDIYTLYCMNYPSSLALLRELSLSPPA-ALWLQERQAQLR-HSLPLQSFLLKPVQRILKYHLLLQELGKHWAegPGTG 202
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLKKNPKfRAFLEELEANPEcRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP--PDHP 156

                          170       180
                   ....*....|....*....|
gi 1195569754  203 GREMVEEAIVSMTAVAWYIN 222
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 47-223 1.89e-47

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 167.48  E-value: 1.89e-47
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754    47 VAREIVETERAYVRDLRSIVEDYLGPLLDGGVLgLSVEQVGTLFANIEDIYEFSSELLEDLENSSSAGG-----IAECFV 121
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-LSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdsverIGDVFL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   122 QRSEDFDIYTLYCMNYPSSLALLRELSLSPPAALWLQERQAQLRH-SLPLQSFLLKPVQRILKYHLLLQELGKHWAEGPG 200
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159

                           170       180
                    ....*....|....*....|...
gi 1195569754   201 TggREMVEEAIVSMTAVAWYIND 223
Cdd:smart00325  160 D--REDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 46-222 7.63e-46

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 162.85  E-value: 7.63e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   46 RVAREIVETERAYVRDLRSIVEDYLGPLLDGGvLGLSVEQVGTLFANIEDIYEFSSELLEDLENS-----SSAGGIAECF 120
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKEL-LPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewdKSGPRIGDVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  121 VQRSEDFDIYTLYCMNYPSSLALLRELSlspPAALWLQERQAQLR---HSLPLQSFLLKPVQRILKYHLLLQELGKHWAE 197
Cdd:cd00160     82 LKLAPFFKIYSEYCSNHPDALELLKKLK---KFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|....*
gi 1195569754  198 GPgtGGREMVEEAIVSMTAVAWYIN 222
Cdd:cd00160    159 GH--EDREDLKKALEAIKEVASQVN 181
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 278-350 9.50e-07

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 48.31  E-value: 9.50e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   278 LFLFSRMLLVAKRR--GLEYTYKGHIFCCNLSVSESPR-----DPLGFKVSdlTIPKHRHLLQAKNQEEKRLWIHCLQRL 350
Cdd:smart00233   23 FVLFNSTLLYYKSKkdKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIK--TSDRKTLLLQAESEEEREKWVEALRKA 100
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 50-211 1.83e-06

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 52.59  E-value: 1.83e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   50 EIVETERAYVRDLRSIVEDYLGPLLDGGVLGLSVEQ--VGTLFANIEDIYEFSSELLEDLEN----SSSAGGIAECFVQR 123
Cdd:COG5422    491 EVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARRnfIKHVFANINEIYAVNSKLLKALTNrqclSPIVNGIADIFLDY 570

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  124 SEDFDIYTLYCMNYPSSLALL-RELSLSPPAALWLQERQaQLRHSLP--LQSFLLKPVQRILKYHLLLQELGKHwaEGPG 200
Cdd:COG5422    571 VPKFEPFIKYGASQPYAKYEFeREKSVNPNFARFDHEVE-RLDESRKleLDGYLTKPTTRLARYPLLLEEVLKF--TDPD 647

                          170
                   ....*....|.
gi 1195569754  201 TGGREMVEEAI 211
Cdd:COG5422    648 NPDTEDIPKVI 658
PHA03247 PHA03247
large tegument protein UL36; Provisional
 384-845 1.44e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 49.94  E-value: 1.44e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  384 PLTPPLGSPRPRDaRSFTPGRrnTAPSP-GPSVIRRGRRQSEPvkdpyvmfPQNAKPGFKHAGSEGELYPPESQPPVSGS 462
Cdd:PHA03247  2553 PPLPPAAPPAAPD-RSVPPPR--PAPRPsEPAVTSRARRPDAP--------PQSARPRAPVDDRGDPRGPAPPSPLPPDT 2621

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  463 APPEdledagPPTLDPSgtsiteeilellnQRGLRDPGPSTHDIPKFPGDSQVPGDSETltfqALPSRDSSEEEEEEEEG 542
Cdd:PHA03247  2622 HAPD------PPPPSPS-------------PAANEPDPHPPPTVPPPERPRDDPAPGRV----SRPRRARRLGRAAQASS 2678

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  543 lemDERGPSPlhvlegleSSIAAEMPSIPCLTKIPDVPNLPEIPSRCEIPEGSRLPSLSDISDVF-EMPCLPAIPSVPNT 621
Cdd:PHA03247  2679 ---PPQRPRR--------RAARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASpALPAAPAPPAVPAG 2747

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  622 PSLSSTPTLscdswlQGPLQEPAEAPATRRELFSGSNPGKLGEPPSGGKAGPEEDEEGVSFTDFQPQDVTQHQGFPDELA 701
Cdd:PHA03247  2748 PATPGGPAR------PARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPA 2821

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  702 FRSCSEIRSAWQALEQGQLARPGFPEPLLILEDSDL-GGD----SGSGKAGAPSSERTASRVRELARLYSERIQQ----- 771
Cdd:PHA03247  2822 ASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVApGGDvrrrPPSRSPAAKPAAPARPPVRRLARPAVSRSTEsfalp 2901

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1195569754  772 ---MQRAETRASANAPRRRPRVLAQPQPSPCLPQE-QAEPGLLPAFGHvlvcelafplTCAQESVPLGPAVWVQAAIP 845
Cdd:PHA03247  2902 pdqPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPpRPQPPLAPTTDP----------AGAGEPSGAVPQPWLGALVP 2969
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 278-350 1.39e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.16  E-value: 1.39e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  278 LFLFSRMLLV--AKRRGLEYTYKGHIF-----CCNLSVSESPRDPLGFKV-SDLTIPKHRHLLQAKNQEEKRLWIHCLQR 349
Cdd:pfam00169   23 FVLFDGSLLYykDDKSGKSKEPKGSISlsgceVVEVVASDSPKRKFCFELrTGERTGKRTYLLQAESEEERKDWIKAIQS 102


                   .
gi 1195569754  350 L 350
Cdd:pfam00169  103 A 103
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 710-1094 1.99e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 42.45  E-value: 1.99e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  710 SAWQALEQGQLARPGFPEPLLILEDSDLGGDSGSGKAGAPSSERTASRVRELARLYSERIQQMQRAETRASANAPRRRPR 789
Cdd:pfam03154  161 SAQQQILQTQPPVLQAQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQSTAAPHTLIQQTPTLHPQ 240

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  790 VLA------QPQPSPCLPQEQAEPGLLPAFGHVLVCELAFPLTCaqesvplGPAVwVQAAIPLSKQGGSPDGQGLHVSNL 863
Cdd:pfam03154  241 RLPsphpplQPMTQPPPPSQVSPQPLPQPSLHGQMPPMPHSLQT-------GPSH-MQHPVPPQPFPLTPQSSQSQVPPG 312

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  864 PKQDLPGIHVSAATLLPEQGGSRHVQAPAATPLPKQEGPLhlqvpalttfsdqghPEIQVPATTPLPEhrshmvIPAPST 943
Cdd:pfam03154  313 PSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSM---------------PHIKPPPTTPIPQ------LPNPQS 371

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  944 afcpeQGHCADIHVPTTPALPKEICSDFTVSVTTPVPKQegHLDSESPTNIPLTKQggSRDVQGP---DPVCSQPiQPLS 1020
Cdd:pfam03154  372 -----HKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTH--HPPSAHPPPLQLMPQ--SQQLPPPpaqPPVLTQS-QSLP 441

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1195569754 1021 WHGSSLDPQGPGDTLPPLPCHLPDLQIPGTSP--LPAHGshldhrIPANAPLSLSQELPDTQVPATTPLPLPQVLT 1094
Cdd:pfam03154  442 PPAASHPPTSGLHQVPSQSPFPQHPFVPGGPPpiTPPSG------PPTSTSSAMPGIQPPSSASVSSSGPVPAAVS 511
 
Name Accession Description Interval E-value
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 204-354 4.96e-61

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 205.28  E-value: 4.96e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  204 REMVEEAIVSMTAVAWYINDMKRKQEHAARLQEVQRRLGGWTGPELSAFGELVLEgafrggGGGGPRLRGGERLLFLFSR 283
Cdd:cd13243      1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLE------GTFRMAGAKNERLLFLFDK 74

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1195569754  284 MLLVAKRR-GLEYTYKGHIFCCNLSVSES-PRDPLGFKVSDLTIPKHRHLLQAKNQEEKRLWIHCLQRLFFEN 354
Cdd:cd13243     75 MLLITKKReDGILQYKTHIMCSNLMLSESiPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 47-222 1.08e-50

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 176.72  E-value: 1.08e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   47 VAREIVETERAYVRDLRSIVEDYLGPLLDggVLGLSVEQVGTLFANIEDIYEFS-SELLEDL-ENSSSAGGIAECFVQRS 124
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSK--PLSESEEEIKTIFSNIEEIYELHrQLLLEELlKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  125 EDFDIYTLYCMNYPSSLALLRELSLSPPA-ALWLQERQAQLR-HSLPLQSFLLKPVQRILKYHLLLQELGKHWAegPGTG 202
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLKKNPKfRAFLEELEANPEcRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP--PDHP 156

                          170       180
                   ....*....|....*....|
gi 1195569754  203 GREMVEEAIVSMTAVAWYIN 222
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 47-223 1.89e-47

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 167.48  E-value: 1.89e-47
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754    47 VAREIVETERAYVRDLRSIVEDYLGPLLDGGVLgLSVEQVGTLFANIEDIYEFSSELLEDLENSSSAGG-----IAECFV 121
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-LSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdsverIGDVFL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   122 QRSEDFDIYTLYCMNYPSSLALLRELSLSPPAALWLQERQAQLRH-SLPLQSFLLKPVQRILKYHLLLQELGKHWAEGPG 200
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159

                           170       180
                    ....*....|....*....|...
gi 1195569754   201 TggREMVEEAIVSMTAVAWYIND 223
Cdd:smart00325  160 D--REDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 46-222 7.63e-46

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 162.85  E-value: 7.63e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   46 RVAREIVETERAYVRDLRSIVEDYLGPLLDGGvLGLSVEQVGTLFANIEDIYEFSSELLEDLENS-----SSAGGIAECF 120
Cdd:cd00160      3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKEL-LPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewdKSGPRIGDVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  121 VQRSEDFDIYTLYCMNYPSSLALLRELSlspPAALWLQERQAQLR---HSLPLQSFLLKPVQRILKYHLLLQELGKHWAE 197
Cdd:cd00160     82 LKLAPFFKIYSEYCSNHPDALELLKKLK---KFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180
                   ....*....|....*....|....*
gi 1195569754  198 GPgtGGREMVEEAIVSMTAVAWYIN 222
Cdd:cd00160    159 GH--EDREDLKKALEAIKEVASQVN 181
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 278-350 9.50e-07

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 48.31  E-value: 9.50e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   278 LFLFSRMLLVAKRR--GLEYTYKGHIFCCNLSVSESPR-----DPLGFKVSdlTIPKHRHLLQAKNQEEKRLWIHCLQRL 350
Cdd:smart00233   23 FVLFNSTLLYYKSKkdKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIK--TSDRKTLLLQAESEEEREKWVEALRKA 100
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 50-211 1.83e-06

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 52.59  E-value: 1.83e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754   50 EIVETERAYVRDLRSIVEDYLGPLLDGGVLGLSVEQ--VGTLFANIEDIYEFSSELLEDLEN----SSSAGGIAECFVQR 123
Cdd:COG5422    491 EVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARRnfIKHVFANINEIYAVNSKLLKALTNrqclSPIVNGIADIFLDY 570

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  124 SEDFDIYTLYCMNYPSSLALL-RELSLSPPAALWLQERQaQLRHSLP--LQSFLLKPVQRILKYHLLLQELGKHwaEGPG 200
Cdd:COG5422    571 VPKFEPFIKYGASQPYAKYEFeREKSVNPNFARFDHEVE-RLDESRKleLDGYLTKPTTRLARYPLLLEEVLKF--TDPD 647

                          170
                   ....*....|.
gi 1195569754  201 TGGREMVEEAI 211
Cdd:COG5422    648 NPDTEDIPKVI 658
PHA03247 PHA03247
large tegument protein UL36; Provisional
 384-845 1.44e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 49.94  E-value: 1.44e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  384 PLTPPLGSPRPRDaRSFTPGRrnTAPSP-GPSVIRRGRRQSEPvkdpyvmfPQNAKPGFKHAGSEGELYPPESQPPVSGS 462
Cdd:PHA03247  2553 PPLPPAAPPAAPD-RSVPPPR--PAPRPsEPAVTSRARRPDAP--------PQSARPRAPVDDRGDPRGPAPPSPLPPDT 2621

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  463 APPEdledagPPTLDPSgtsiteeilellnQRGLRDPGPSTHDIPKFPGDSQVPGDSETltfqALPSRDSSEEEEEEEEG 542
Cdd:PHA03247  2622 HAPD------PPPPSPS-------------PAANEPDPHPPPTVPPPERPRDDPAPGRV----SRPRRARRLGRAAQASS 2678

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  543 lemDERGPSPlhvlegleSSIAAEMPSIPCLTKIPDVPNLPEIPSRCEIPEGSRLPSLSDISDVF-EMPCLPAIPSVPNT 621
Cdd:PHA03247  2679 ---PPQRPRR--------RAARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASpALPAAPAPPAVPAG 2747

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  622 PSLSSTPTLscdswlQGPLQEPAEAPATRRELFSGSNPGKLGEPPSGGKAGPEEDEEGVSFTDFQPQDVTQHQGFPDELA 701
Cdd:PHA03247  2748 PATPGGPAR------PARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPA 2821

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  702 FRSCSEIRSAWQALEQGQLARPGFPEPLLILEDSDL-GGD----SGSGKAGAPSSERTASRVRELARLYSERIQQ----- 771
Cdd:PHA03247  2822 ASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVApGGDvrrrPPSRSPAAKPAAPARPPVRRLARPAVSRSTEsfalp 2901

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1195569754  772 ---MQRAETRASANAPRRRPRVLAQPQPSPCLPQE-QAEPGLLPAFGHvlvcelafplTCAQESVPLGPAVWVQAAIP 845
Cdd:PHA03247  2902 pdqPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPpRPQPPLAPTTDP----------AGAGEPSGAVPQPWLGALVP 2969
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 278-347 2.64e-05

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 44.07  E-value: 2.64e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1195569754  278 LFLFSRMLLVAK-RRGLEYTYKGHIF---CCNLSVSESPRDPLGFKvsdLTIPKHRHL-LQAKNQEEKRLWIHCL 347
Cdd:cd00821     21 FVLFEGVLLYYKsKKDSSYKPKGSIPlsgILEVEEVSPKERPHCFE---LVTPDGRTYyLQADSEEERQEWLKAL 92
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
 229-349 3.26e-05

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269931  Cd Length: 138  Bit Score: 44.94  E-value: 3.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  229 EHAARLQEVQRRLGGWTGPELSafgELVLEGAFRGGGGGGPRLRGGERLLFLFSRMLLVAKR---RGLEYTYKGHIFCCN 305
Cdd:cd01224      2 ENLEKLAAWQSTVEGWEGEDLS---DRSSELIHSGELTKISAGRAQERTFFLFDHQLVYCKKdllRRKNYIYKGRIDTDN 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1195569754  306 LSVsESPRD--------PL--GFKVSDLTIPKHrHLLQAKNQEEKRLWIHCLQR 349
Cdd:cd01224     79 MEI-EDLPDgkddesgvTVknAWKIYNASKNKW-YVLCAKSAEEKQRWLEAFAE 130
PHA03247 PHA03247
large tegument protein UL36; Provisional
 378-809 3.56e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 3.56e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  378 SKPVLEPLTPPLGSPRPRDARSFTPGRRNTAP------SPGPSVIRRGRRQSEPVKDPYVMFPQNA--KPGFKHA-GSEG 448
Cdd:PHA03247  2617 LPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPperprdDPAPGRVSRPRRARRLGRAAQASSPPQRprRRAARPTvGSLT 2696

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  449 ELYPPESQPPVSGSAPPEdledAGPPTLDPSGTSiteeilellNQRGLRDPGPSTHDIPKFPGDSQVPGDSETLTFQALP 528
Cdd:PHA03247  2697 SLADPPPPPPTPEPAPHA----LVSATPLPPGPA---------AARQASPALPAAPAPPAVPAGPATPGGPARPARPPTT 2763

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  529 SRDSSEEEEEeeeglemDERGPSPLHVLEGLESSIAAEMPSIPCLTKIPDVPNLPEIPSRCEIPEGSRLPSLSdisdvfe 608
Cdd:PHA03247  2764 AGPPAPAPPA-------APAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLP------- 2829

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  609 mPCLPAIPSVPNTPSLSSTPTLSCDSWL--------QGPLQEPAEAPATRRelfsgsnpgklgEPPSGGKAGPEEDEEGV 680
Cdd:PHA03247  2830 -PPTSAQPTAPPPPPGPPPPSLPLGGSVapggdvrrRPPSRSPAAKPAAPA------------RPPVRRLARPAVSRSTE 2896

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  681 SFTdfQPQDVTQHQGFPDeLAFRSCSEIRSAWQALEQGQLARPGFPEPLLILEDSDLGGDSGSGKAGAPSSERTASRVRE 760
Cdd:PHA03247  2897 SFA--LPPDQPERPPQPQ-APPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVA 2973

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*....
gi 1195569754  761 LARlyseriqqmqraeTRASANAPRRRprvlaQPQPSPCLPQEQAEPGL 809
Cdd:PHA03247  2974 VPR-------------FRVPQPAPSRE-----APASSTPPLTGHSLSRV 3004
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 278-350 1.39e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.16  E-value: 1.39e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  278 LFLFSRMLLV--AKRRGLEYTYKGHIF-----CCNLSVSESPRDPLGFKV-SDLTIPKHRHLLQAKNQEEKRLWIHCLQR 349
Cdd:pfam00169   23 FVLFDGSLLYykDDKSGKSKEPKGSISlsgceVVEVVASDSPKRKFCFELrTGERTGKRTYLLQAESEEERKDWIKAIQS 102


                   .
gi 1195569754  350 L 350
Cdd:pfam00169  103 A 103
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 279-350 5.18e-04

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270061  Cd Length: 140  Bit Score: 41.48  E-value: 5.18e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  279 FLFSRMLLVA----KRRGLE---YTYKGHIFCCNLSVSES-PRDPLGF--KVSDLTIPKHRHLLQAKNQEEKRLWIHCLQ 348
Cdd:cd13241     42 FLFEQIIIFSeilgKKTQFSnpgYIYKNHIKVNKMSLEENvDGDPLRFalKSRDPNNPSETFILQAASPEVRQEWVDTIN 121


                   ..
gi 1195569754  349 RL 350
Cdd:cd13241    122 QI 123
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 710-1094 1.99e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 42.45  E-value: 1.99e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  710 SAWQALEQGQLARPGFPEPLLILEDSDLGGDSGSGKAGAPSSERTASRVRELARLYSERIQQMQRAETRASANAPRRRPR 789
Cdd:pfam03154  161 SAQQQILQTQPPVLQAQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQSTAAPHTLIQQTPTLHPQ 240

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  790 VLA------QPQPSPCLPQEQAEPGLLPAFGHVLVCELAFPLTCaqesvplGPAVwVQAAIPLSKQGGSPDGQGLHVSNL 863
Cdd:pfam03154  241 RLPsphpplQPMTQPPPPSQVSPQPLPQPSLHGQMPPMPHSLQT-------GPSH-MQHPVPPQPFPLTPQSSQSQVPPG 312

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  864 PKQDLPGIHVSAATLLPEQGGSRHVQAPAATPLPKQEGPLhlqvpalttfsdqghPEIQVPATTPLPEhrshmvIPAPST 943
Cdd:pfam03154  313 PSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSM---------------PHIKPPPTTPIPQ------LPNPQS 371

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  944 afcpeQGHCADIHVPTTPALPKEICSDFTVSVTTPVPKQegHLDSESPTNIPLTKQggSRDVQGP---DPVCSQPiQPLS 1020
Cdd:pfam03154  372 -----HKHPPHLSGPSPFQMNSNLPPPPALKPLSSLSTH--HPPSAHPPPLQLMPQ--SQQLPPPpaqPPVLTQS-QSLP 441

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1195569754 1021 WHGSSLDPQGPGDTLPPLPCHLPDLQIPGTSP--LPAHGshldhrIPANAPLSLSQELPDTQVPATTPLPLPQVLT 1094
Cdd:pfam03154  442 PPAASHPPTSGLHQVPSQSPFPQHPFVPGGPPpiTPPSG------PPTSTSSAMPGIQPPSSASVSSSGPVPAAVS 511
PTZ00449 PTZ00449
104 kDa microneme/rhoptry antigen; Provisional
 479-628 2.02e-03

104 kDa microneme/rhoptry antigen; Provisional


Pssm-ID: 185628 [Multi-domain]  Cd Length: 943  Bit Score: 42.37  E-value: 2.02e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  479 SGTSITEEILELLNQRGLRDPGPSTHDI------PKFPGDSQVP----GDSETLTFQALPSRDSSEEEEEEEEG-LEMDE 547
Cdd:PTZ00449   477 SKIQFTQEIKKLIKKSKKKLAPIEEEDSdkhdepPEGPEASGLPpkapGDKEGEEGEHEDSKESDEPKEGGKPGeTKEGE 556

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1195569754  548 RGPSPLHVLEglessiaaEMPS-IPCLTKIPDVPNLPEIPSRCEIPEGSR---------------LPSLSDISDVFEMPC 611
Cdd:PTZ00449   557 VGKKPGPAKE--------HKPSkIPTLSKKPEFPKDPKHPKDPEEPKKPKrprsaqrptrpkspkLPELLDIPKSPKRPE 628

                          170
                   ....*....|....*..
gi 1195569754  612 LPAIPSVPNTPSLSSTP 628
Cdd:PTZ00449   629 SPKSPKRPPPPQRPSSP 645
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
 278-347 2.14e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275410  Cd Length: 92  Bit Score: 38.62  E-value: 2.14e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1195569754  278 LFLFSRMLL--VAKRRGL--EYTYKGHIFCCNLSVSES--PRDPLGFKVSDltipKHRHL-LQAKNQEEKRLWIHCL 347
Cdd:cd13328     20 LFLFNDMLLycVPKLSLVgqKFSVRNRLDVAGMKVREPvnENYPHTFKISG----KERSLeLQASSAEEKDEWIQAI 92
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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