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
                 ....*....|....*....|....*....|....*..
gi 225543124 222 LTSGRWFLRQGWLLVVPPTGePRPRMFFLFSDVLLMA 258
Cdd:cd01220    2 VQPGREFIREGCLQKLSKKG-LQQRMFFLFSDVLLYT 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543124    27 ARELLETERRYQEQLGLVATYFLRILKAKGT-LRPPELQTLFGTWELIYAASLELLPYLEE--GQW-------GLGLQGF 96
Cdd:smart00325   2 LKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEEriEEWddsveriGDVFLKL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543124    97 CPHLELYAQFAANAERSQTTLQaQLKKNKRFRRFVKLQEGRPEFRGLQLQDLLPLPLQRLQQYENLVVALAENTVPNSPD 176
Cdd:smart00325  82 EEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170       180
                   ....*....|....*....|
gi 225543124   177 YQQLTRAARLVSETAQKVHA 196
Cdd:smart00325 161 REDLKKALKAIKELANQVNE 180

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.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 225543124 222 LTSGRWFLRQGWLLVVPPTGePRPRMFFLFSDVLLMA 258
Cdd:cd01220    2 VQPGREFIREGCLQKLSKKG-LQQRMFFLFSDVLLYT 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543124    27 ARELLETERRYQEQLGLVATYFLRILKAKGT-LRPPELQTLFGTWELIYAASLELLPYLEE--GQW-------GLGLQGF 96
Cdd:smart00325   2 LKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEEriEEWddsveriGDVFLKL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543124    97 CPHLELYAQFAANAERSQTTLQaQLKKNKRFRRFVKLQEGRPEFRGLQLQDLLPLPLQRLQQYENLVVALAENTVPNSPD 176
Cdd:smart00325  82 EEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                          170       180
                   ....*....|....*....|
gi 225543124   177 YQQLTRAARLVSETAQKVHA 196
Cdd:smart00325 161 REDLKKALKAIKELANQVNE 180

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.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 225543124 222 LTSGRWFLRQGWLLVVPPTGePRPRMFFLFSDVLLMA 258
Cdd:cd01220    2 VQPGREFIREGCLQKLSKKG-LQQRMFFLFSDVLLYT 37

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 225543124 230 RQGWLLVVPPTG--EPRPRMFFLFSDVLLMAKPRpplhllKSGTFVCRALYPMSQCHLSRVFGHSGGPCGglLSLSFP-H 306
Cdd:cd00821    1 KEGYLLKRGGGGlkSWKKRWFVLFEGVLLYYKSK------KDSSYKPKGSIPLSGILEVEEVSPKERPHC--FELVTPdG 72

                         90       100
                 ....*....|....*....|
gi 225543124 307 EKLLLMSTDQEELSQWHHSL 326
Cdd:cd00821   73 RTYYLQADSEEERQEWLKAL 92

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543124  230 RQGWLL--VVPPTGEPRPRMFFLFSDVLLMAKPRPPLHLlksgtFVCRALYPMSQCHLSRVFGHS--GGPCGGLLSLS-- 303
Cdd:pfam00169   3 KEGWLLkkGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKS-----KEPKGSISLSGCEVVEVVASDspKRKFCFELRTGer 77

                          90       100
                  ....*....|....*....|....*...
gi 225543124  304 FPHEKLLLMSTDQEELSQWHHSLTLAIR 331
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSAIR 105