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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222 225 GRWFLRQGWLLVVppTG-EPRPRMFFLFSDALLMAKPRPPLHLLK-------SGTFVCRalypMTQCQLSRVFghsggpc 296
Cdd:cd13389   11 GRKLIKEGELMKV--SRkEMQPRYFFLFNDCLLYTTPVQSSGMLKlnnelplSGMKVKL----PEDEEYSNEF------- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 308153222 297 gGLLSL--SFpheklLLMSTDQEELSQWYHSLTQAIRSQKNSAHRSVPA 343
Cdd:cd13389   78 -QIISTkrSF-----TLIASSEEERDEWVKALSRAIEEHTKKQRTFAEN 120

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222    27 ARELLETERRYQEQLGLVATYFLGILKAKGT-LRPPERQTLFGTWELIYAASLELLPYLEE--GQW-------GPGLQGF 96
Cdd:smart00325   2 LKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEEriEEWddsveriGDVFLKL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222    97 CPHLELYTQFAANAERSQTTLqEQLKKNKRFRRFVRLQEGRPEFRGLQLQDLLPLPLQRLQQYENLVVALAENTVPNSSD 176
Cdd:smart00325  82 EEFFKIYSEYCSNHPDALELL-KKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170       180
                   ....*....|....*....|
gi 308153222   177 YQQLTRAARLVSETAQKVHA 196
Cdd:smart00325 161 REDLKKALKAIKELANQVNE 180

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222 225 GRWFLRQGWLLVVppTG-EPRPRMFFLFSDALLMAKPRPPLHLLK-------SGTFVCRalypMTQCQLSRVFghsggpc 296
Cdd:cd13389   11 GRKLIKEGELMKV--SRkEMQPRYFFLFNDCLLYTTPVQSSGMLKlnnelplSGMKVKL----PEDEEYSNEF------- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 308153222 297 gGLLSL--SFpheklLLMSTDQEELSQWYHSLTQAIRSQKNSAHRSVPA 343
Cdd:cd13389   78 -QIISTkrSF-----TLIASSEEERDEWVKALSRAIEEHTKKQRTFAEN 120

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222    27 ARELLETERRYQEQLGLVATYFLGILKAKGT-LRPPERQTLFGTWELIYAASLELLPYLEE--GQW-------GPGLQGF 96
Cdd:smart00325   2 LKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEEriEEWddsveriGDVFLKL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222    97 CPHLELYTQFAANAERSQTTLqEQLKKNKRFRRFVRLQEGRPEFRGLQLQDLLPLPLQRLQQYENLVVALAENTVPNSSD 176
Cdd:smart00325  82 EEFFKIYSEYCSNHPDALELL-KKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170       180
                   ....*....|....*....|
gi 308153222   177 YQQLTRAARLVSETAQKVHA 196
Cdd:smart00325 161 REDLKKALKAIKELANQVNE 180

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222 225 GRWFLRQGWLLVVppTG-EPRPRMFFLFSDALLMAKPRPPLHLLK-------SGTFVCRalypMTQCQLSRVFghsggpc 296
Cdd:cd13389   11 GRKLIKEGELMKV--SRkEMQPRYFFLFNDCLLYTTPVQSSGMLKlnnelplSGMKVKL----PEDEEYSNEF------- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 308153222 297 gGLLSL--SFpheklLLMSTDQEELSQWYHSLTQAIRSQKNSAHRSVPA 343
Cdd:cd13389   78 -QIISTkrSF-----TLIASSEEERDEWVKALSRAIEEHTKKQRTFAEN 120

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222 230 RQGWLLVVPPTG--EPRPRMFFLFSDALLMAKPRpplhllKSGTFVCRALYPMTQCQLSRVFGHSGGPCGglLSLSFP-H 306
Cdd:cd00821    1 KEGYLLKRGGGGlkSWKKRWFVLFEGVLLYYKSK------KDSSYKPKGSIPLSGILEVEEVSPKERPHC--FELVTPdG 72

                         90       100
                 ....*....|....*....|
gi 308153222 307 EKLLLMSTDQEELSQWYHSL 326
Cdd:cd00821   73 RTYYLQADSEEERQEWLKAL 92

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308153222 177 YQQLTRAarLVSETAQKVHaIGQNRKNEQHLLRV---QALLSGRKAKGLTSGRWFLRQGWLLVvppTGEPRPRMFFLFSD 253
Cdd:cd13243    1 RSVVEEA--LDTMTQVAWH-INDMKRKHEHAVRVqeiQSLLDGWEGPELTTYGDLVLEGTFRM---AGAKNERLLFLFDK 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 308153222 254 ALLMAKPRPPlhllksGTFVCRALypMTQCQLSRVFGHSGGPCG-GLLSLSFPHEKLLLMSTDQEELSQWYHSLTQAI 330
Cdd:cd13243   75 MLLITKKRED------GILQYKTH--IMCSNLMLSESIPKEPLSfQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLI 144

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 308153222 203 NEQHLLRVQALLSGRKAKGLTSGRWFLRQGWLLVVPPTGePRPRMFFLFSDAL 255
Cdd:cd01218    5 NRRRIAAVESCFGGSGQPLVKPGRVLVGEGVLTKVCRKK-PKPRQFFLFNDIL 56