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Conserved domains on  [gi|21356889|ref|NP_648101|]
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Rho guanine nucleotide exchange factor 4, isoform A [Drosophila melanogaster]

Protein Classification

RhoGEF and PH domain-containing protein( domain architecture ID 12002256)

protein containing domains RhoGEF, PH-like, and PH

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 74-244 4.16e-46

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: 160.93  E-value: 4.16e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889    74 AIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDCSNHTLLFGQIEMIHNLNGE-FLRELEAN---MENVAHAFLKMAPF 149
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQlLLEELLKEwisIQRIGDIFLKFAPG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   150 FKLYSVYAFDYRGALFIIQDLISKNPVFRKFLEQTESRPEVQR-KLNSLMIVPIQRVPRYKLLLEQVLLYTSPADADYKL 228
Cdd:pfam00621  81 FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDYED 160

                         170
                  ....*....|....*.
gi 21356889   229 LKESVKEIEATASHIN 244
Cdd:pfam00621 161 LKKALEAIKEVAKQIN 176
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 269-311 1.71e-05

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13389:

Pssm-ID: 473070  Cd Length: 124  Bit Score: 44.57  E-value: 1.71e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21356889 269 NIVKPSRRVIKEGVLQKITHKgtEIK-RYCVLMSDIFMYCKMIK 311
Cdd:cd13389   6 NIVKPGRKLIKEGELMKVSRK--EMQpRYFFLFNDCLLYTTPVQ 47
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 277-374 1.83e-03

PH domain; PH stands for pleckstrin homology.


:

Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 38.31  E-value: 1.83e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   277 VIKEGVLQKITH--KGTEIKRYCVLMSDIFMYCKmikerapNTVVENSLECCCIFPLKKCKVYEMLPGN-------FKLT 347
Cdd:pfam00169   1 VVKEGWLLKKGGgkKKSWKKRYFVLFDGSLLYYK-------DDKSGKSKEPKGSISLSGCEVVEVVASDspkrkfcFELR 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 21356889   348 ----CQSDGIIFGSGDVQLSRTWVGFIRDAI 374
Cdd:pfam00169  74 tgerTGKRTYLLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 74-244 4.16e-46

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: 160.93  E-value: 4.16e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889    74 AIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDCSNHTLLFGQIEMIHNLNGE-FLRELEAN---MENVAHAFLKMAPF 149
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQlLLEELLKEwisIQRIGDIFLKFAPG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   150 FKLYSVYAFDYRGALFIIQDLISKNPVFRKFLEQTESRPEVQR-KLNSLMIVPIQRVPRYKLLLEQVLLYTSPADADYKL 228
Cdd:pfam00621  81 FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDYED 160

                         170
                  ....*....|....*.
gi 21356889   229 LKESVKEIEATASHIN 244
Cdd:pfam00621 161 LKKALEAIKEVAKQIN 176
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 71-244 6.76e-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: 138.58  E-value: 6.76e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889  71 RRQAIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDC-SNHTLLFGQIEMIHNLNGEFLRELEANMEN-------VAHA 142
Cdd:cd00160   1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSpEEVELLFGNIEEIYEFHRIFLKSLEERVEEwdksgprIGDV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889 143 FLKMAPFFKLYSVYAFDYRGALFIIQDLISKNPVFRKFLEQTESRPEvQRKLNSLMIVPIQRVPRYKLLLEQVLLYTSPA 222
Cdd:cd00160  81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESECG-RLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159

                       170       180
                ....*....|....*....|..
gi 21356889 223 DADYKLLKESVKEIEATASHIN 244
Cdd:cd00160 160 HEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 74-244 7.31e-37

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: 135.89  E-value: 7.31e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889     74 AIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDCSN-HTLLFGQIEMIHNLNGEFLRELEANMEN-------VAHAFLK 145
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNeLETLFGNIEEIYEFHRDFLDELEERIEEwddsverIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889    146 MAPFFKLYSVYAFDYRGALFIIQDLiSKNPVFRKFLEQTESRPEVQR-KLNSLMIVPIQRVPRYKLLLEQVLLYTSPADA 224
Cdd:smart00325  81 LEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159

                          170       180
                   ....*....|....*....|
gi 21356889    225 DYKLLKESVKEIEATASHIN 244
Cdd:smart00325 160 DREDLKKALKAIKELANQVN 179
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 71-285 5.60e-14

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 75.70  E-value: 5.60e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   71 RRQAIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDCSNH----TLLFGQIEMIHNLNGEFL------RELEANMENVA 140
Cdd:COG5422  485 RQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARrnfiKHVFANINEIYAVNSKLLkaltnrQCLSPIVNGIA 564

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889  141 HAFLKMAPFFKLYSVYAFDYRGALFIIQDLISKNPVFRKFLEQTESRPEVQRK-LNSLMIVPIQRVPRYKLLLEQVLLYT 219
Cdd:COG5422  565 DIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLeLDGYLTKPTTRLARYPLLLEEVLKFT 644

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 21356889  220 SPADADYKLLKESVKEIEATASHINTCVEEQEITQYLIHLQNSLVNRtPNIVK-----PSRRVIKEGVLQK 285
Cdd:COG5422  645 DPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFK-PEYVNlglndEYRKIIFKGVLKR 714
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
 269-311 1.71e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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: 275424  Cd Length: 124  Bit Score: 44.57  E-value: 1.71e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21356889 269 NIVKPSRRVIKEGVLQKITHKgtEIK-RYCVLMSDIFMYCKMIK 311
Cdd:cd13389   6 NIVKPGRKLIKEGELMKVSRK--EMQpRYFFLFNDCLLYTTPVQ 47
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 277-375 8.01e-05

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: 42.15  E-value: 8.01e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889    277 VIKEGVLQKIT--HKGTEIKRYCVLMSDIFMYCKMIKErapntvvENSLECCCIFPLKKCKVYEMLPGN-------FKLT 347
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYKSKKD-------KKSYKPKGSIDLSGCTVREAPDPDsskkphcFEIK 73

                           90       100
                   ....*....|....*....|....*....
gi 21356889    348 CQSDG-IIFGSGDVQLSRTWVGFIRDAID 375
Cdd:smart00233  74 TSDRKtLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 277-374 1.83e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 38.31  E-value: 1.83e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   277 VIKEGVLQKITH--KGTEIKRYCVLMSDIFMYCKmikerapNTVVENSLECCCIFPLKKCKVYEMLPGN-------FKLT 347
Cdd:pfam00169   1 VVKEGWLLKKGGgkKKSWKKRYFVLFDGSLLYYK-------DDKSGKSKEPKGSISLSGCEVVEVVASDspkrkfcFELR 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 21356889   348 ----CQSDGIIFGSGDVQLSRTWVGFIRDAI 374
Cdd:pfam00169  74 tgerTGKRTYLLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 74-244 4.16e-46

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: 160.93  E-value: 4.16e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889    74 AIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDCSNHTLLFGQIEMIHNLNGE-FLRELEAN---MENVAHAFLKMAPF 149
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQlLLEELLKEwisIQRIGDIFLKFAPG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   150 FKLYSVYAFDYRGALFIIQDLISKNPVFRKFLEQTESRPEVQR-KLNSLMIVPIQRVPRYKLLLEQVLLYTSPADADYKL 228
Cdd:pfam00621  81 FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDYED 160

                         170
                  ....*....|....*.
gi 21356889   229 LKESVKEIEATASHIN 244
Cdd:pfam00621 161 LKKALEAIKEVAKQIN 176
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 71-244 6.76e-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: 138.58  E-value: 6.76e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889  71 RRQAIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDC-SNHTLLFGQIEMIHNLNGEFLRELEANMEN-------VAHA 142
Cdd:cd00160   1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSpEEVELLFGNIEEIYEFHRIFLKSLEERVEEwdksgprIGDV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889 143 FLKMAPFFKLYSVYAFDYRGALFIIQDLISKNPVFRKFLEQTESRPEvQRKLNSLMIVPIQRVPRYKLLLEQVLLYTSPA 222
Cdd:cd00160  81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESECG-RLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159

                       170       180
                ....*....|....*....|..
gi 21356889 223 DADYKLLKESVKEIEATASHIN 244
Cdd:cd00160 160 HEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 74-244 7.31e-37

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: 135.89  E-value: 7.31e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889     74 AIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDCSN-HTLLFGQIEMIHNLNGEFLRELEANMEN-------VAHAFLK 145
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNeLETLFGNIEEIYEFHRDFLDELEERIEEwddsverIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889    146 MAPFFKLYSVYAFDYRGALFIIQDLiSKNPVFRKFLEQTESRPEVQR-KLNSLMIVPIQRVPRYKLLLEQVLLYTSPADA 224
Cdd:smart00325  81 LEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159

                          170       180
                   ....*....|....*....|
gi 21356889    225 DYKLLKESVKEIEATASHIN 244
Cdd:smart00325 160 DREDLKKALKAIKELANQVN 179
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 71-285 5.60e-14

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 75.70  E-value: 5.60e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   71 RRQAIQEIISSEKSYLEQLELLMNFFVRPLKEQAIIDCSNH----TLLFGQIEMIHNLNGEFL------RELEANMENVA 140
Cdd:COG5422  485 RQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARrnfiKHVFANINEIYAVNSKLLkaltnrQCLSPIVNGIA 564

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889  141 HAFLKMAPFFKLYSVYAFDYRGALFIIQDLISKNPVFRKFLEQTESRPEVQRK-LNSLMIVPIQRVPRYKLLLEQVLLYT 219
Cdd:COG5422  565 DIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLeLDGYLTKPTTRLARYPLLLEEVLKFT 644

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 21356889  220 SPADADYKLLKESVKEIEATASHINTCVEEQEITQYLIHLQNSLVNRtPNIVK-----PSRRVIKEGVLQK 285
Cdd:COG5422  645 DPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFK-PEYVNlglndEYRKIIFKGVLKR 714
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
 269-311 1.71e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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: 275424  Cd Length: 124  Bit Score: 44.57  E-value: 1.71e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21356889 269 NIVKPSRRVIKEGVLQKITHKgtEIK-RYCVLMSDIFMYCKMIK 311
Cdd:cd13389   6 NIVKPGRKLIKEGELMKVSRK--EMQpRYFFLFNDCLLYTTPVQ 47
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 277-375 8.01e-05

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: 42.15  E-value: 8.01e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889    277 VIKEGVLQKIT--HKGTEIKRYCVLMSDIFMYCKMIKErapntvvENSLECCCIFPLKKCKVYEMLPGN-------FKLT 347
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYKSKKD-------KKSYKPKGSIDLSGCTVREAPDPDsskkphcFEIK 73

                           90       100
                   ....*....|....*....|....*....
gi 21356889    348 CQSDG-IIFGSGDVQLSRTWVGFIRDAID 375
Cdd:smart00233  74 TSDRKtLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 277-374 1.83e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 38.31  E-value: 1.83e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21356889   277 VIKEGVLQKITH--KGTEIKRYCVLMSDIFMYCKmikerapNTVVENSLECCCIFPLKKCKVYEMLPGN-------FKLT 347
Cdd:pfam00169   1 VVKEGWLLKKGGgkKKSWKKRYFVLFDGSLLYYK-------DDKSGKSKEPKGSISLSGCEVVEVVASDspkrkfcFELR 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 21356889   348 ----CQSDGIIFGSGDVQLSRTWVGFIRDAI 374
Cdd:pfam00169  74 tgerTGKRTYLLQAESEEERKDWIKAIQSAI 104
 
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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