Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6/90Cool-2) and beta Pix (GEF7/p85Cool-1). betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity. 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 1907190365 165 VTYMSQVTIQCAGSEEKNERYLLLFPNLLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSENHRNAFEISGSMIERILVS 244
Cdd:cd01225     1 VIHMSQVAVQNTGCQEKKERYFLLFPHVLLMLSASPRMSGFIYEGKLPLTGISVNRLEDTEGIKNAFEISGPLIERIVVI 80

                          90
                  ....*....|....*....
gi 1907190365 245 CTSQQDLHEWVEHLQKQTK 263
Cdd:cd01225    81 CNSQQDQQEWLEHLQQQTK 99

Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6/90Cool-2) and beta Pix (GEF7/p85Cool-1). betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity. 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 1907190365 165 VTYMSQVTIQCAGSEEKNERYLLLFPNLLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSENHRNAFEISGSMIERILVS 244
Cdd:cd01225     1 VIHMSQVAVQNTGCQEKKERYFLLFPHVLLMLSASPRMSGFIYEGKLPLTGISVNRLEDTEGIKNAFEISGPLIERIVVI 80

                          90
                  ....*....|....*....
gi 1907190365 245 CTSQQDLHEWVEHLQKQTK 263
Cdd:cd01225    81 CNSQQDQQEWLEHLQQQTK 99

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 1907190365    1 MGNLEEISSFQQVLVQSLEECTK-SPEAQQRVGGCFLSLMPqMRTLYLAYCANHPSAVSVLTE--HSEDLGEFMETKGAS 77
Cdd:smart00325  43 FGNIEEIYEFHRDFLDELEERIEeWDDSVERIGDVFLKLEE-FFKIYSEYCSNHPDALELLKKlkKNPRFQKFLKEIESS 121

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907190365   78 SPGI-LVLTTGLSKPFMRLDKYPTLLKELERHMEDYHPDRQDIQKSMTAFKNLSAQCQE 135
Cdd:smart00325 122 PQCRrLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHEDREDLKKALKAIKELANQVNE 180

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907190365  199 SPRMSGFIYQGKLPTTGMTITKLEDSEN--HRNAFEISGSMIERILVSCTSQQDLHEWVEHLQKQTK 263
Cdd:smart00233  36 KKDKKSYKPKGSIDLSGCTVREAPDPDSskKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102

Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6/90Cool-2) and beta Pix (GEF7/p85Cool-1). betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity. 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 1907190365 165 VTYMSQVTIQCAGSEEKNERYLLLFPNLLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSENHRNAFEISGSMIERILVS 244
Cdd:cd01225     1 VIHMSQVAVQNTGCQEKKERYFLLFPHVLLMLSASPRMSGFIYEGKLPLTGISVNRLEDTEGIKNAFEISGPLIERIVVI 80

                          90
                  ....*....|....*....
gi 1907190365 245 CTSQQDLHEWVEHLQKQTK 263
Cdd:cd01225    81 CNSQQDQQEWLEHLQQQTK 99

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 1907190365    1 MGNLEEISSFQQVLVQSLEECTK-SPEAQQRVGGCFLSLMPqMRTLYLAYCANHPSAVSVLTE--HSEDLGEFMETKGAS 77
Cdd:smart00325  43 FGNIEEIYEFHRDFLDELEERIEeWDDSVERIGDVFLKLEE-FFKIYSEYCSNHPDALELLKKlkKNPRFQKFLKEIESS 121

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907190365   78 SPGI-LVLTTGLSKPFMRLDKYPTLLKELERHMEDYHPDRQDIQKSMTAFKNLSAQCQE 135
Cdd:smart00325 122 PQCRrLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHEDREDLKKALKAIKELANQVNE 180

Pleckstrin homology domain containing family N member 1Pleckstrin homology-like domain; Not much is known about PLEKHN1. It is found in a wide range of animals including humans, green anole, frog, and zebrafish. It 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907190365 160 KTLGSVTYMSQVTIQCAGSEEKNERYLLLFPNLLLMLSASPrmSGFIYQGKLPTTGMTITkLEDSENHRNAFEISGSMIE 239
Cdd:cd13323     2 ESLGSITCVSKVKLQHLPFQEQHDRLLVLYPSSLIILSEES--DGLCFKGELPLNAIQVN-FEENEKKIRSFLIEGRLIN 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907190365 240 RILVSCTSQQDLHEWVEHLqKQTKVTSVSNPTIKPHSVPSHTLP 283
Cdd:cd13323    79 TIRVSCLSYEDYQDWILCL-KTAQVRNGDSSLPGSSSFYGSTQP 121

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907190365 201 RMSGFIYQGKLPTTGMTITKLEDSENH------RNAFEISGSMIER-ILVSCTSQQDLHEWVEHLQK 260
Cdd:cd01224    64 RRKNYIYKGRIDTDNMEIEDLPDGKDDesgvtvKNAWKIYNASKNKwYVLCAKSAEEKQRWLEAFAE 130

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907190365 183 ERYLLLFPNLLLMLSASPRMSGFIYQGKLPTTGMTITKL--EDSENHRNAFEISGSMI---ERILVSCTSQQDLHEWVEH 257
Cdd:pfam00169  20 KRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVvaSDSPKRKFCFELRTGERtgkRTYLLQAESEEERKDWIKA 99

                  ....*.
gi 1907190365 258 LQKQTK 263
Cdd:pfam00169 100 IQSAIR 105