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Conserved domains on  [gi|38505170|ref|NP_008840|]
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ras-specific guanine nucleotide-releasing factor 2 [Homo sapiens]

Protein Classification

guanine nucleotide exchange factor( domain architecture ID 10881747)

Ras guanine nucleotide exchange factor activates Ras-like small GTPases by mediating the replacement of GDP with GTP

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
998-1234 5.00e-91

Guanine nucleotide exchange factor for Ras-like small GTPases;


:

Pssm-ID: 214539  Cd Length: 242  Bit Score: 293.00  E-value: 5.00e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     998 FESLSAMELAEQITLLDHVIFRSIPYEEFLGQGWMKLDKNERTPY-IMKTSQHFNDMSNLVASQIMNYADVSSRANAIEK 1076
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPLnLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    1077 WVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNCN-PPAVPYLG 1155
Cdd:smart00147   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNlPPCIPFLG 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    1156 MYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHIIREIRQFQQTSYRIDHQPKVAQYLLD--KDLIIDEDTLYELSLKIEP 1233
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQPYNLRPNRSDIQSLLQqlLDHLDEEEELYQLSLKIEP 240


                    .
gi 38505170    1234 R 1234
Cdd:smart00147  241 R 241
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
 19-158 6.50e-86

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. 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: 270081  Cd Length: 136  Bit Score: 274.69  E-value: 6.50e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   19 ARKEGTKRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAPPRAGAGQggvrDALDKQYY 98
Cdd:cd13261    1 ARKDGTKRGYLSKKTSDSGKWHERWFALYQNLLFYFENESSSRPSGLYLLEGCYCERLPTPKGALKGK----DHLEKQHY 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   99 FTVLFGHEGQKPLELRCEEEQDGKEWMEAIHQASYADILIEREVLMQKYIHLVQIVETEK 158
Cdd:cd13261   77 FTISFRHENQRQYELRAETESDCDEWVEAIKQASFNKLLLQKEELEQKYLHLLQIVESEK 136
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 247-428 6.61e-42

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: 151.68  E-value: 6.61e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     247 IVFTMVEAESEYVHQLYILVNGFLRPLRMAASskkpPISHDDVSSIFLNSETIMFLHEIFHQGLKARIANWPTL--ILAD 324
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSveRIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     325 LFDILLPMLNIYQEFVRNHQYSLQVLANCKQNRDFDKLLKQYEANPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPH 404
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPE 156

                           170       180
                    ....*....|....*....|....
gi 38505170     405 EHVERKSLEFAKSKLEELSRVMHD 428
Cdd:smart00325  157 DHEDREDLKKALKAIKELANQVNE 180
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
 638-686 1.35e-13

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


:

Pssm-ID: 459873  Cd Length: 104  Bit Score: 68.10  E-value: 1.35e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 38505170    638 QIRYASVERLLERLTDLRF-LSIDFLNTFLHTYRIFTTAAVVLGKLSDIY 686
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRImLDDSFLSTFLLTYRSFTTPAELLELLIERY 50
REM super family cl02520
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 901-972 2.14e-13

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


The actual alignment was detected with superfamily member smart00229:

Pssm-ID: 470601  Cd Length: 127  Bit Score: 68.13  E-value: 2.14e-13
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38505170     901 ERTCDKEFIIRRTATNRVLNVLRHWVSKHAQDFELNNELKMNVLNLLEEVLRDPdlLPQERKAAANILRALS 972
Cdd:smart00229   58 PESWVEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEK--YPGLVTSLLNLLRRLS 127
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 480-588 2.40e-06

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: 47.16  E-value: 2.40e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     480 VRLGSLSLKKEG------ERQCFLFTKHFLICTRSSGGKLHLLKtgGVLSLIDCTLIEEPDASDDDSKGSgqvfghldFK 553
Cdd:smart00233    2 IKEGWLYKKSGGgkkswkKRYFVLFNSTLLYYKSKKDKKSYKPK--GSIDLSGCTVREAPDPDSSKKPHC--------FE 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 38505170     554 IVVEPPDaaafTVVLLAPSRQEKAAWMSDISQCVD 588
Cdd:smart00233   72 IKTSDRK----TLLLQAESEEEREKWVEALRKAIA 102
 
Name Accession Description Interval E-value
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
998-1234 5.00e-91

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 293.00  E-value: 5.00e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     998 FESLSAMELAEQITLLDHVIFRSIPYEEFLGQGWMKLDKNERTPY-IMKTSQHFNDMSNLVASQIMNYADVSSRANAIEK 1076
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPLnLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    1077 WVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNCN-PPAVPYLG 1155
Cdd:smart00147   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNlPPCIPFLG 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    1156 MYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHIIREIRQFQQTSYRIDHQPKVAQYLLD--KDLIIDEDTLYELSLKIEP 1233
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQPYNLRPNRSDIQSLLQqlLDHLDEEEELYQLSLKIEP 240


                    .
gi 38505170    1234 R 1234
Cdd:smart00147  241 R 241
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 998-1230 7.98e-90

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 289.54  E-value: 7.98e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  998 FESLSAMELAEQITLLDHVIFRSIPYEEFLGQGWMKLDKN-ERTPYIMKTSQHFNDMSNLVASQIMNYADVSSRANAIEK 1076
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNiHLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170 1077 WVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNC--NPPAVPYL 1154
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVgpNPPCVPFL 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38505170 1155 GMYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHIIREIRQFQQTSYRIDHQPKVAQYLLDKDLIID-EDTLYELSLK 1230
Cdd:cd00155  161 GVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILnEDELYELSLE 237
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
 19-158 6.50e-86

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. 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: 270081  Cd Length: 136  Bit Score: 274.69  E-value: 6.50e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   19 ARKEGTKRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAPPRAGAGQggvrDALDKQYY 98
Cdd:cd13261    1 ARKDGTKRGYLSKKTSDSGKWHERWFALYQNLLFYFENESSSRPSGLYLLEGCYCERLPTPKGALKGK----DHLEKQHY 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   99 FTVLFGHEGQKPLELRCEEEQDGKEWMEAIHQASYADILIEREVLMQKYIHLVQIVETEK 158
Cdd:cd13261   77 FTISFRHENQRQYELRAETESDCDEWVEAIKQASFNKLLLQKEELEQKYLHLLQIVESEK 136
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1005-1183 1.53e-75

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 247.51  E-value: 1.53e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   1005 ELAEQITLLDHVIFRSIPYEEFLGQGWMKLDKNERTPYIMKTSQHFNDMSNLVASQIMNYADVSSRANAIEKWVAVADIC 1084
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   1085 RCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNCNPPAVPYLGMYLTDLAFI 1164
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                          170
                   ....*....|....*....
gi 38505170   1165 EEGTPNFTEEGLVNFSKMR 1183
Cdd:pfam00617  161 EEGNPDFLEGGLINFEKRR 179
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 247-428 6.61e-42

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: 151.68  E-value: 6.61e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     247 IVFTMVEAESEYVHQLYILVNGFLRPLRMAASskkpPISHDDVSSIFLNSETIMFLHEIFHQGLKARIANWPTL--ILAD 324
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSveRIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     325 LFDILLPMLNIYQEFVRNHQYSLQVLANCKQNRDFDKLLKQYEANPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPH 404
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPE 156

                           170       180
                    ....*....|....*....|....
gi 38505170     405 EHVERKSLEFAKSKLEELSRVMHD 428
Cdd:smart00325  157 DHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 244-424 4.44e-38

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: 140.90  E-value: 4.44e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  244 RNQIVFTMVEAESEYVHQLYILVNGFLRPLRMAASskkpPISHDDVSSIFLNSETIMFLHEIFHQGLKARIANW--PTLI 321
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL----PLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdkSGPR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  322 LADLFDILLPMLNIYQEFVRNHQYSLQVLANCKQ-NRDFDKLLKQYEANpaCEGRMLETFLTYPMFQIPRYIITLHELLA 400
Cdd:cd00160   77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLK 154

                        170       180
                 ....*....|....*....|....
gi 38505170  401 HTPHEHVERKSLEFAKSKLEELSR 424
Cdd:cd00160  155 HTPDGHEDREDLKKALEAIKEVAS 178
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 247-422 4.76e-33

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: 126.26  E-value: 4.76e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    247 IVFTMVEAESEYVHQLYILVNGFLRPLRMAASSkkppiSHDDVSSIFLNSETIMFLHEIFHqgLKARIANWP-TLILADL 325
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSE-----SEEEIKTIFSNIEEIYELHRQLL--LEELLKEWIsIQRIGDI 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    326 FDILLPMLNIYQEFVRNHQYSLQVLANCKQ-NRDFDKLLKQYEANPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPH 404
Cdd:pfam00621   74 FLKFAPGFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPP 153

                          170
                   ....*....|....*...
gi 38505170    405 EHVERKSLEFAKSKLEEL 422
Cdd:pfam00621  154 DHPDYEDLKKALEAIKEV 171
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 24-133 8.48e-14

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 68.74  E-value: 8.48e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     24 TKRGFLSKKT-AEASRWHEKWFALYQNVLFYFE---GEQSCRPAGMYLLEGCSCERTPAPPRAgagqggvrdalDKQYYF 99
Cdd:pfam00169    2 VKEGWLLKKGgGKKKSWKKRYFVLFDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSP-----------KRKFCF 70

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 38505170    100 TVLFGHEGQKP-LELRCEEEQDGKEWMEAIHQASY 133
Cdd:pfam00169   71 ELRTGERTGKRtYLLQAESEEERKDWIKAIQSAIR 105
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
 638-686 1.35e-13

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 459873  Cd Length: 104  Bit Score: 68.10  E-value: 1.35e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 38505170    638 QIRYASVERLLERLTDLRF-LSIDFLNTFLHTYRIFTTAAVVLGKLSDIY 686
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRImLDDSFLSTFLLTYRSFTTPAELLELLIERY 50
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 24-133 2.08e-13

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: 67.57  E-value: 2.08e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170      24 TKRGFLSKKTAEASR-WHEKWFALYQNVLFYFE---GEQSCRPAGMYLLEGCSCERTPAPpragagqggvrDALDKQYYF 99
Cdd:smart00233    2 IKEGWLYKKSGGGKKsWKKRYFVLFNSTLLYYKskkDKKSYKPKGSIDLSGCTVREAPDP-----------DSSKKPHCF 70

                            90       100       110
                    ....*....|....*....|....*....|....
gi 38505170     100 TVLfgHEGQKPLELRCEEEQDGKEWMEAIHQASY 133
Cdd:smart00233   71 EIK--TSDRKTLLLQAESEEEREKWVEALRKAIA 102
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 901-972 2.14e-13

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 68.13  E-value: 2.14e-13
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38505170     901 ERTCDKEFIIRRTATNRVLNVLRHWVSKHAQDFELNNELKMNVLNLLEEVLRDPdlLPQERKAAANILRALS 972
Cdd:smart00229   58 PESWVEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEK--YPGLVTSLLNLLRRLS 127
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 643-689 3.45e-08

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 53.19  E-value: 3.45e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 38505170  643 SVERLLERLTD-LRFLSIDFLNTFLHTYRIFTTAAVVLGKLSDIYKRP 689
Cdd:cd06224    1 TLEALIEHLTStFDMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIA 48
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 480-588 2.40e-06

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: 47.16  E-value: 2.40e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     480 VRLGSLSLKKEG------ERQCFLFTKHFLICTRSSGGKLHLLKtgGVLSLIDCTLIEEPDASDDDSKGSgqvfghldFK 553
Cdd:smart00233    2 IKEGWLYKKSGGgkkswkKRYFVLFNSTLLYYKSKKDKKSYKPK--GSIDLSGCTVREAPDPDSSKKPHC--------FE 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 38505170     554 IVVEPPDaaafTVVLLAPSRQEKAAWMSDISQCVD 588
Cdd:smart00233   72 IKTSDRK----TLLLQAESEEEREKWVEALRKAIA 102
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 894-959 3.33e-06

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 47.41  E-value: 3.33e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38505170  894 PPGFNNTERTCDKEFIIRRtatnRVLNVLRHWVSKHAQDFELNNELKMNVLNLLEEVLRDPDLLPQ 959
Cdd:cd06224   50 PENLEYNDWDKKKSKPIRL----RVLNVLRTWVENYPYDFFDDEELLELLEEFLNRLVQEGALLQE 111
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 480-587 1.28e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 45.25  E-value: 1.28e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    480 VRLGSLSLKKEG------ERQCFLFTKHFLICTRSSGGKLHLLKtgGVLSLIDCTLIEEPDASDDDSKGSgqvfghldFK 553
Cdd:pfam00169    2 VKEGWLLKKGGGkkkswkKRYFVLFDGSLLYYKDDKSGKSKEPK--GSISLSGCEVVEVVASDSPKRKFC--------FE 71

                           90       100       110
                   ....*....|....*....|....*....|....
gi 38505170    554 IVVEPPDAAAfTVVLLAPSRQEKAAWMSDISQCV 587
Cdd:pfam00169   72 LRTGERTGKR-TYLLQAESEEERKDWIKAIQSAI 104
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 635-690 2.57e-05

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 45.02  E-value: 2.57e-05
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 38505170     635 KVPQIRYASVERLLERLTD-LRFLSIDFLNTFLHTYRIFTTAAVVLGKLSDIYKRPF 690
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEaFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIP 57
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 460-591 2.70e-03

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. 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: 269928  Cd Length: 109  Bit Score: 38.84  E-value: 2.70e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  460 FIRQGSLIqvpsvergKLSKvrlgslslKKEGERQCFLFTKHFLICTRSSGGKLHLlKTGGVLSLIDcTLIEEPDAsddd 539
Cdd:cd01220    8 FIREGCLQ--------KLSK--------KGLQQRMFFLFSDVLLYTSRSPTPSLQF-KVHGQLPLRG-LMVEESEP---- 65

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 38505170  540 skgsgQVFGHLDFKIvveppDAAAFTVVLLAPSRQEKAAWMSDISQCVDNIR 591
Cdd:cd01220   66 -----EWGVAHCFTI-----YGGNRALTVAASSEEEKERWLEDLQRAIDAAK 107
 
Name Accession Description Interval E-value
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
998-1234 5.00e-91

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 293.00  E-value: 5.00e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     998 FESLSAMELAEQITLLDHVIFRSIPYEEFLGQGWMKLDKNERTPY-IMKTSQHFNDMSNLVASQIMNYADVSSRANAIEK 1076
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPLnLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    1077 WVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNCN-PPAVPYLG 1155
Cdd:smart00147   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNlPPCIPFLG 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    1156 MYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHIIREIRQFQQTSYRIDHQPKVAQYLLD--KDLIIDEDTLYELSLKIEP 1233
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQPYNLRPNRSDIQSLLQqlLDHLDEEEELYQLSLKIEP 240


                    .
gi 38505170    1234 R 1234
Cdd:smart00147  241 R 241
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 998-1230 7.98e-90

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 289.54  E-value: 7.98e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  998 FESLSAMELAEQITLLDHVIFRSIPYEEFLGQGWMKLDKN-ERTPYIMKTSQHFNDMSNLVASQIMNYADVSSRANAIEK 1076
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNiHLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170 1077 WVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNC--NPPAVPYL 1154
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVgpNPPCVPFL 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38505170 1155 GMYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHIIREIRQFQQTSYRIDHQPKVAQYLLDKDLIID-EDTLYELSLK 1230
Cdd:cd00155  161 GVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILnEDELYELSLE 237
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
 19-158 6.50e-86

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. 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: 270081  Cd Length: 136  Bit Score: 274.69  E-value: 6.50e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   19 ARKEGTKRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAPPRAGAGQggvrDALDKQYY 98
Cdd:cd13261    1 ARKDGTKRGYLSKKTSDSGKWHERWFALYQNLLFYFENESSSRPSGLYLLEGCYCERLPTPKGALKGK----DHLEKQHY 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   99 FTVLFGHEGQKPLELRCEEEQDGKEWMEAIHQASYADILIEREVLMQKYIHLVQIVETEK 158
Cdd:cd13261   77 FTISFRHENQRQYELRAETESDCDEWVEAIKQASFNKLLLQKEELEQKYLHLLQIVESEK 136
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1005-1183 1.53e-75

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 247.51  E-value: 1.53e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   1005 ELAEQITLLDHVIFRSIPYEEFLGQGWMKLDKNERTPYIMKTSQHFNDMSNLVASQIMNYADVSSRANAIEKWVAVADIC 1084
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   1085 RCLHNYNGVLEITSALNRSAIYRLKKTWAKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNCNPPAVPYLGMYLTDLAFI 1164
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                          170
                   ....*....|....*....
gi 38505170   1165 EEGTPNFTEEGLVNFSKMR 1183
Cdd:pfam00617  161 EEGNPDFLEGGLINFEKRR 179
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 247-428 6.61e-42

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: 151.68  E-value: 6.61e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     247 IVFTMVEAESEYVHQLYILVNGFLRPLRMAASskkpPISHDDVSSIFLNSETIMFLHEIFHQGLKARIANWPTL--ILAD 324
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSveRIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     325 LFDILLPMLNIYQEFVRNHQYSLQVLANCKQNRDFDKLLKQYEANPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPH 404
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPE 156

                           170       180
                    ....*....|....*....|....
gi 38505170     405 EHVERKSLEFAKSKLEELSRVMHD 428
Cdd:smart00325  157 DHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 244-424 4.44e-38

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: 140.90  E-value: 4.44e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  244 RNQIVFTMVEAESEYVHQLYILVNGFLRPLRMAASskkpPISHDDVSSIFLNSETIMFLHEIFHQGLKARIANW--PTLI 321
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL----PLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdkSGPR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  322 LADLFDILLPMLNIYQEFVRNHQYSLQVLANCKQ-NRDFDKLLKQYEANpaCEGRMLETFLTYPMFQIPRYIITLHELLA 400
Cdd:cd00160   77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLK 154

                        170       180
                 ....*....|....*....|....
gi 38505170  401 HTPHEHVERKSLEFAKSKLEELSR 424
Cdd:cd00160  155 HTPDGHEDREDLKKALEAIKEVAS 178
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 247-422 4.76e-33

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: 126.26  E-value: 4.76e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    247 IVFTMVEAESEYVHQLYILVNGFLRPLRMAASSkkppiSHDDVSSIFLNSETIMFLHEIFHqgLKARIANWP-TLILADL 325
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSE-----SEEEIKTIFSNIEEIYELHRQLL--LEELLKEWIsIQRIGDI 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    326 FDILLPMLNIYQEFVRNHQYSLQVLANCKQ-NRDFDKLLKQYEANPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPH 404
Cdd:pfam00621   74 FLKFAPGFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPP 153

                          170
                   ....*....|....*...
gi 38505170    405 EHVERKSLEFAKSKLEEL 422
Cdd:pfam00621  154 DHPDYEDLKKALEAIKEV 171
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 25-133 3.25e-14

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single 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: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 70.34  E-value: 3.25e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   25 KRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAppragagqggvrdalDKQYYFTVLFG 104
Cdd:cd13288   10 KEGYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGDREPLGVIVLEGCTVELAED---------------AEPYAFAIRFD 74

                         90       100
                 ....*....|....*....|....*....
gi 38505170  105 HEGQKPLELRCEEEQDGKEWMEAIHQASY 133
Cdd:cd13288   75 GPGARSYVLAAENQEDMESWMKALSRASY 103
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 24-133 8.48e-14

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 68.74  E-value: 8.48e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     24 TKRGFLSKKT-AEASRWHEKWFALYQNVLFYFE---GEQSCRPAGMYLLEGCSCERTPAPPRAgagqggvrdalDKQYYF 99
Cdd:pfam00169    2 VKEGWLLKKGgGKKKSWKKRYFVLFDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSP-----------KRKFCF 70

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 38505170    100 TVLFGHEGQKP-LELRCEEEQDGKEWMEAIHQASY 133
Cdd:pfam00169   71 ELRTGERTGKRtYLLQAESEEERKDWIKAIQSAIR 105
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
 638-686 1.35e-13

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 459873  Cd Length: 104  Bit Score: 68.10  E-value: 1.35e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 38505170    638 QIRYASVERLLERLTDLRF-LSIDFLNTFLHTYRIFTTAAVVLGKLSDIY 686
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRImLDDSFLSTFLLTYRSFTTPAELLELLIERY 50
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 24-133 2.08e-13

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: 67.57  E-value: 2.08e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170      24 TKRGFLSKKTAEASR-WHEKWFALYQNVLFYFE---GEQSCRPAGMYLLEGCSCERTPAPpragagqggvrDALDKQYYF 99
Cdd:smart00233    2 IKEGWLYKKSGGGKKsWKKRYFVLFNSTLLYYKskkDKKSYKPKGSIDLSGCTVREAPDP-----------DSSKKPHCF 70

                            90       100       110
                    ....*....|....*....|....*....|....
gi 38505170     100 TVLfgHEGQKPLELRCEEEQDGKEWMEAIHQASY 133
Cdd:smart00233   71 EIK--TSDRKTLLLQAESEEEREKWVEALRKAIA 102
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 901-972 2.14e-13

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 68.13  E-value: 2.14e-13
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38505170     901 ERTCDKEFIIRRTATNRVLNVLRHWVSKHAQDFELNNELKMNVLNLLEEVLRDPdlLPQERKAAANILRALS 972
Cdd:smart00229   58 PESWVEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEK--YPGLVTSLLNLLRRLS 127
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
 6-133 4.21e-13

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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: 270078  Cd Length: 123  Bit Score: 67.35  E-value: 4.21e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    6 RYNEGHALYLAF-LARKEGTKRGFLSKKTAEASRWHEKWFALYQNVLFYF---EGEQSCRPAGMYLLEGCSCERTPAPPR 81
Cdd:cd13258    2 RFNEKELAALSSqPAEKEGKIAERQMGGPKKSEVFKERWFKLKGNLLFYFrtnEFGDCSEPIGAIVLENCRVQMEEITEK 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 38505170   82 AGAgqggvrdaldkqyyFTVLFGHEGQKPLELRCEEEQDGKEWMEAIHQASY 133
Cdd:cd13258   82 PFA--------------FSIVFNDEPEKKYIFSCRSEEQCEQWIEALRQASY 119
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 24-132 1.50e-08

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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: 270118  Cd Length: 113  Bit Score: 53.95  E-value: 1.50e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   24 TKRGFLSKKTA---EASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCerTPAPPRagagqggvrdALDKQYYFT 100
Cdd:cd13308   10 IHSGTLTKKGGsqkTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNR--RAAEER----------TSKLKFVFK 77

                         90       100       110
                 ....*....|....*....|....*....|..
gi 38505170  101 VLFGHEGQKPLELRCEEEQDGKEWMEAIHQAS 132
Cdd:cd13308   78 IIHLSPDHRTWYFAAKSEDEMSEWMEYIRREI 109
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 643-689 3.45e-08

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 53.19  E-value: 3.45e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 38505170  643 SVERLLERLTD-LRFLSIDFLNTFLHTYRIFTTAAVVLGKLSDIYKRP 689
Cdd:cd06224    1 TLEALIEHLTStFDMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIA 48
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
 25-134 5.28e-08

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 241529  Cd Length: 116  Bit Score: 52.26  E-value: 5.28e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   25 KRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSC-ERTPAPPRAGagqggvrdaldkQYYFTVLF 103
Cdd:cd13378    5 KAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVnELPPNPEEPG------------KHLFEILP 72

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 38505170  104 GHEGQK--------PLELRCEEEQDGKEWMEAIHQASYA 134
Cdd:cd13378   73 GGAGDRekvpmnheAFLLMANSQSDMEDWVKAIRRVIWA 111
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 25-128 9.65e-08

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: 51.00  E-value: 9.65e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   25 KRGFLSKKTAEAS-RWHEKWFALYQNVLFYF--EGEQSCRPAGMYLLEGCsCERTPAPPragagqggvrdaLDKQYYFTV 101
Cdd:cd00821    1 KEGYLLKRGGGGLkSWKKRWFVLFEGVLLYYksKKDSSYKPKGSIPLSGI-LEVEEVSP------------KERPHCFEL 67

                         90       100
                 ....*....|....*....|....*..
gi 38505170  102 LfgHEGQKPLELRCEEEQDGKEWMEAI 128
Cdd:cd00821   68 V--TPDGRTYYLQADSEEERQEWLKAL 92
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 24-132 6.94e-07

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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: 270068  Cd Length: 104  Bit Score: 48.81  E-value: 6.94e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   24 TKRGFLSKKTAEASR-WHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAPPRAGagqggvrdaldKQYYFTVl 102
Cdd:cd13248    8 VMSGWLHKQGGSGLKnWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEIS-----------RKFAFKA- 75

                         90       100       110
                 ....*....|....*....|....*....|
gi 38505170  103 fGHEGQKPLELRCEEEQDGKEWMEAIHQAS 132
Cdd:cd13248   76 -EHANMRTYYFAADTAEEMEQWMNAMSLAA 104
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 25-72 2.27e-06

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. 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: 270113  Cd Length: 108  Bit Score: 47.37  E-value: 2.27e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 38505170   25 KRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCS 72
Cdd:cd13301    5 KEGYLVKKGHVVNNWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCT 52
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 480-588 2.40e-06

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: 47.16  E-value: 2.40e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170     480 VRLGSLSLKKEG------ERQCFLFTKHFLICTRSSGGKLHLLKtgGVLSLIDCTLIEEPDASDDDSKGSgqvfghldFK 553
Cdd:smart00233    2 IKEGWLYKKSGGgkkswkKRYFVLFNSTLLYYKSKKDKKSYKPK--GSIDLSGCTVREAPDPDSSKKPHC--------FE 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 38505170     554 IVVEPPDaaafTVVLLAPSRQEKAAWMSDISQCVD 588
Cdd:smart00233   72 IKTSDRK----TLLLQAESEEEREKWVEALRKAIA 102
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 894-959 3.33e-06

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 47.41  E-value: 3.33e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38505170  894 PPGFNNTERTCDKEFIIRRtatnRVLNVLRHWVSKHAQDFELNNELKMNVLNLLEEVLRDPDLLPQ 959
Cdd:cd06224   50 PENLEYNDWDKKKSKPIRL----RVLNVLRTWVENYPYDFFDDEELLELLEEFLNRLVQEGALLQE 111
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
 22-134 3.37e-06

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 270083  Cd Length: 114  Bit Score: 47.38  E-value: 3.37e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   22 EGTKRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAPPragagqggvrDALDKqYYFTV 101
Cdd:cd13263    2 RPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNP----------EEPGK-FLFEI 70

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 38505170  102 LFGHEGQKPLE------LRCEEEQDGKEWMEAIHQASYA 134
Cdd:cd13263   71 IPGGGGDRMTSnhdsylLMANSQAEMEEWVKVIRRVIGS 109
PH_INPP4A_INPP4B cd13272
Type I inositol 3,4-bisphosphate 4-phosphatase and Type II inositol 3,4-bisphosphate ...
 6-136 5.79e-06

Type I inositol 3,4-bisphosphate 4-phosphatase and Type II inositol 3,4-bisphosphate 4-phosphatase Pleckstrin homology (PH) domain; INPP4A (also called Inositol polyphosphate 4-phosphatase type I) and INPP4B (also called Inositol polyphosphate 4-phosphatase type II) both catalyze the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate and inositol 1,3,4-trisphosphate. They differ in that INPP4A additionally catalyzes the hydrolysis of the 4-position phosphate of inositol 3,4-bisphosphate, while INPP4B catalyzes the hydrolysis of the 4-position phosphate of inositol 1,4-bisphosphate. They both have a single PH domain followed by a C2 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: 270091  Cd Length: 144  Bit Score: 47.40  E-value: 5.79e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    6 RYNEGHALYLAFLA----RKEG----TKR--GFLSKktAEASrwHEKWFALYQNVLFYFEG-EQSCRPAGMYLLEGCSCE 74
Cdd:cd13272    2 RFNKQELATLASQPstkfDKEGlliiTERqeGFFRR--SEGS--LERWCRLRGNLLFYLKSkDPWSEPAGVIVLEQCRPR 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 38505170   75 RTPAPPRAGagqggvrdaldkQYYFTVLFghEGQKPLELRCEEEQDGKEWMEAIHQASYADI 136
Cdd:cd13272   78 IQNDERDSG------------GYPFDLVF--EDGLCQRLATRTEAERLSWVQAIELASYEVI 125
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 480-587 1.28e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 45.25  E-value: 1.28e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170    480 VRLGSLSLKKEG------ERQCFLFTKHFLICTRSSGGKLHLLKtgGVLSLIDCTLIEEPDASDDDSKGSgqvfghldFK 553
Cdd:pfam00169    2 VKEGWLLKKGGGkkkswkKRYFVLFDGSLLYYKDDKSGKSKEPK--GSISLSGCEVVEVVASDSPKRKFC--------FE 71

                           90       100       110
                   ....*....|....*....|....*....|....
gi 38505170    554 IVVEPPDAAAfTVVLLAPSRQEKAAWMSDISQCV 587
Cdd:pfam00169   72 LRTGERTGKR-TYLLQAESEEERKDWIKAIQSAI 104
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 635-690 2.57e-05

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 45.02  E-value: 2.57e-05
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 38505170     635 KVPQIRYASVERLLERLTD-LRFLSIDFLNTFLHTYRIFTTAAVVLGKLSDIYKRPF 690
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEaFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIP 57
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
 25-77 3.50e-05

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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: 270180  Cd Length: 106  Bit Score: 44.08  E-value: 3.50e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 38505170   25 KRGFLSKKTAE----ASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTP 77
Cdd:cd13380    3 KQGYLEKRSKDhsffGSEWQKRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAQMAP 59
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 25-131 9.67e-05

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal 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: 270092  Cd Length: 110  Bit Score: 43.05  E-value: 9.67e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   25 KRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLL-EGCSCErtPAPPRAGagqggvrdaldKQYYFTVlf 103
Cdd:cd13273   10 KKGYLWKKGHLLPTWTERWFVLKPNSLSYYKSEDLKEKKGEIALdSNCCVE--SLPDREG-----------KKCRFLV-- 74

                         90       100
                 ....*....|....*....|....*...
gi 38505170  104 gHEGQKPLELRCEEEQDGKEWMEAIHQA 131
Cdd:cd13273   75 -KTPDKTYELSASDHKTRQEWIAAIQTA 101
PH_SKIP cd13309
SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called ...
 24-132 1.04e-04

SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called PLEKHM2/Pleckstrin homology domain-containing family M member 2) is a soluble cytosolic protein that contains a RUN domain and a PH domain separated by a unstructured linker region. SKIP is a target of the Salmonella effector protein SifA and the SifA-SKIP complex regulates kinesin-1 on the bacterial vacuole. The PH domain of SKIP binds to the N-terminal region of SifA while the N-terminus of SKIP is proposed to bind the TPR domain of the kinesin light chain. The opposite side of the SKIP PH domain is proposed to bind phosphoinositides. TSifA, SKIP, SseJ, and RhoA family GTPases are also thought to promote host membrane tubulation. Recently, it was shown that the lysosomal GTPase Arl8 binds to the kinesin-1 linker SKIP and that both are required for the normal intracellular distribution of lysosomes. Interestingly, two kinesin light chain binding motifs (WD) in SKIP have now been identified to match a consensus sequence for a kinesin light chain binding site found in several proteins including calsyntenin-1/alcadein, caytaxin, and vaccinia virus A36. SKIP has also been shown to interact with Rab1A. 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: 270119  Cd Length: 103  Bit Score: 42.75  E-value: 1.04e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   24 TKRGFLSKKTAEASRWHEKW----FALYQNVLFYFeGEQScrpagmyllegcscERTP--APPRAGAGQGGVRDAL--DK 95
Cdd:cd13309    1 TKEGMLMYKTGTSYLGGETWkpgyFLLKNGVLYQY-PDRS--------------DRLPllSISLGGEQCGGCRRINntER 65

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 38505170   96 QYYFTVLFGheGQKPLELRCEEEQDGKEWMEAIHQAS 132
Cdd:cd13309   66 PHTFELILT--DRSSLELAAPDEYEASEWLQSLCQSA 100
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
 25-77 1.23e-04

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 270086  Cd Length: 106  Bit Score: 42.51  E-value: 1.23e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 38505170   25 KRGFLSKKTAE----ASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTP 77
Cdd:cd13266    3 KAGYLEKRRKDhsffGSEWQKRWCAISKNVFYYYGSDKDKQQKGEFAINGYDVRMNP 59
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
 22-134 1.88e-04

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 241530  Cd Length: 114  Bit Score: 42.27  E-value: 1.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   22 EGTKRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAPPRAGAG------QGGVRDALDK 95
Cdd:cd13379    2 EVIKCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVTEHPCNEEEPGKflfevvPGGDRERMTA 81

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 38505170   96 QYYFTVLFGhegqkplelrcEEEQDGKEWMEAIHQASYA 134
Cdd:cd13379   82 NHETYLLMA-----------STQNDMEDWVKSIRRVIWA 109
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
 27-131 3.27e-04

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. 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: 241448  Cd Length: 100  Bit Score: 41.33  E-value: 3.27e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   27 GFLSKKTAEASRWHEKWFALYQNVLFYFE--GEQSCRPAGMYLLEGCSCERTPAPpragagqggvrdalDKQYYFtvlfg 104
Cdd:cd13294    3 GILYKWVNYGKGWRSRWFVLQDGVLSYYKvhGPDKVKPSGEVHLKVSSIRESRSD--------------DKKFYI----- 63

                         90       100
                 ....*....|....*....|....*..
gi 38505170  105 HEGQKPLELRCEEEQDGKEWMEAIHQA 131
Cdd:cd13294   64 FTGTKTLHLRAESREDRAAWLEALQAA 90
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 21-72 4.24e-04

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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: 270080  Cd Length: 103  Bit Score: 40.79  E-value: 4.24e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 38505170   21 KEGTKRGFLSKKTAEASRWHEKWFALYQN--VLFYFEGEQSCRPAGMYLLEGCS 72
Cdd:cd13260    1 KGIDKKGYLLKKGGKNKKWKNLYFVLEGKeqHLYFFDNEKRTKPKGLIDLSYCS 54
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 23-81 7.32e-04

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. 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: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 40.00  E-value: 7.32e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   23 GTKRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRP-AGMYLLEGCSCERTPAPPR 81
Cdd:cd10573    3 GSKEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDTKPiRVLDLRECSSVQRDYSQGK 62
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 25-131 7.57e-04

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 40.76  E-value: 7.57e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   25 KRGFLSKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCERTPAPPRA------GAGQGGVRDALDKQYY 98
Cdd:cd01252    5 REGWLLKLGGRVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVEDKKKPfcfelySPSNGQVIKACKTDSD 84

                         90       100       110
                 ....*....|....*....|....*....|...
gi 38505170   99 FTVLFGHEGQKPLELRCEEEQDgkEWMEAIHQA 131
Cdd:cd01252   85 GKVVEGNHTVYRISAASEEERD--EWIKSIKAS 115
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 10-55 9.20e-04

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but 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: 275402  Cd Length: 116  Bit Score: 40.30  E-value: 9.20e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 38505170   10 GHALYLAFLARKEGT--KRGFLSKKTAEASRWHEKWFALYQNVLFYFE 55
Cdd:cd13215    6 KHLCFFAYLPKRSGAviKSGYLSKRSKRTLRYTRYWFVLKGDTLSWYN 53
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 30-128 1.59e-03

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. 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: 270135  Cd Length: 91  Bit Score: 38.86  E-value: 1.59e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170   30 SKKTAEASRWHEKWFALYQNVLFYFEGEQSCRPAGMYLLEGCSCerTPAPpragagqggvrDALDKQYYFTVLfgHEGqK 109
Cdd:cd13326    9 RRKGKGGGKWAKRWFVLKGSNLYGFRSQESTKADCVIFLPGFTV--SPAP-----------EVKSRKYAFKVY--HTG-T 72

                         90
                 ....*....|....*....
gi 38505170  110 PLELRCEEEQDGKEWMEAI 128
Cdd:cd13326   73 VFYFAAESQEDMKKWLDLL 91
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 460-591 2.70e-03

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. 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: 269928  Cd Length: 109  Bit Score: 38.84  E-value: 2.70e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  460 FIRQGSLIqvpsvergKLSKvrlgslslKKEGERQCFLFTKHFLICTRSSGGKLHLlKTGGVLSLIDcTLIEEPDAsddd 539
Cdd:cd01220    8 FIREGCLQ--------KLSK--------KGLQQRMFFLFSDVLLYTSRSPTPSLQF-KVHGQLPLRG-LMVEESEP---- 65

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 38505170  540 skgsgQVFGHLDFKIvveppDAAAFTVVLLAPSRQEKAAWMSDISQCVDNIR 591
Cdd:cd01220   66 -----EWGVAHCFTI-----YGGNRALTVAASSEEEKERWLEDLQRAIDAAK 107
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 475-583 4.24e-03

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: 37.91  E-value: 4.24e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38505170  475 GKLSKvrLGSLSLKKEGERQCFLFtKHFLICTRSSGGKLHLLKtgGVLSLIDCTLIEEPDASDDDSKgsgqvfghldFKI 554
Cdd:cd00821    3 GYLLK--RGGGGLKSWKKRWFVLF-EGVLLYYKSKKDSSYKPK--GSIPLSGILEVEEVSPKERPHC----------FEL 67

                         90       100
                 ....*....|....*....|....*....
gi 38505170  555 VVEPPDaaafTVVLLAPSRQEKAAWMSDI 583
Cdd:cd00821   68 VTPDGR----TYYLQADSEEERQEWLKAL 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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