Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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 119591949 182 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 260
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 119591949 261 YTFQASGQALCRGWVDTIYN 280
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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 119591949 182 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 260
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 119591949 261 YTFQASGQALCRGWVDTIYN 280
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119591949   20 FLKgfkmFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLLKSVLR 99
Cdd:pfam00621  74 FLK----FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLK 149

                          90       100
                  ....*....|....*....|....*..
gi 119591949  100 KTEEPRA-KEAVVAMIGSVERFIHHVN 125
Cdd:pfam00621 150 HTPPDHPdYEDLKKALEAIKEVAKQIN 176

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119591949   184 LLLEGSLRMKE--GKDSKMDVYCFLFTDLLLVTKAvKKAERTRVIRPPLLVDKIVCRELRD------PGSFLLIYLNEfh 255
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYKS-KKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDR-- 77

                           90       100
                   ....*....|....*....|....*...
gi 119591949   256 savGAYTFQASGQALCRGWVDTIYNAQN 283
Cdd:smart00233  78 ---KTLLLQAESEEEREKWVEALRKAIA 102

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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 119591949 182 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 260
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 119591949 261 YTFQASGQALCRGWVDTIYN 280
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119591949   20 FLKgfkmFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLLKSVLR 99
Cdd:pfam00621  74 FLK----FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLK 149

                          90       100
                  ....*....|....*....|....*..
gi 119591949  100 KTEEPRA-KEAVVAMIGSVERFIHHVN 125
Cdd:pfam00621 150 HTPPDHPdYEDLKKALEAIKEVAKQIN 176

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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 119591949 183 QLLLEGSLRMKE-GKdsKMDVYCFLFTDLLLVTK----AVKK-----------AERTRVI---------RPPLLVDKIVC 237
Cdd:cd13245    1 QLLHEGPLTLIEsGK--TLDVYLFLFDDMLLITKmkknLKKKkssdsensmpsLELTPLIkeggsytvyKQPIPLDRLCL 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 119591949 238 RELrDP---------GSFLLIYLNEFHSAVGAYTFQASGQALCRGWVDTI 278
Cdd:cd13245   79 HDV-DPneatanglkHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKL 127

Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation. Net1 contains a RhoGEF domain N-terminal to 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 119591949 179 EETRQLLLEGSLRMKEGKDskmdVYCFLFTDLLLVTKAVKKAERT--RVIRPPLLVDKIVCRELRD-----PGSFLLIYL 251
Cdd:cd13224   15 ENSKALLCHGELRNKSGHK----LYVFLFQDILVLTRPVTRNERQsfQVYRQPIPVQELVLEDLQDgdvrmGGSFRGAFS 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 119591949 252 N----------EFH--SAVGAYTFQASGQALCRGWVDTIYNAQNQ 284
Cdd:cd13224   91 NsekaknifrvRFLdpSPGQSHTLQANDVFHKQQWLNCIRTAISP 135

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 119591949 182 RQLLLEGSLrMKEGKDSKMDVYCFLFTDLLLVTKAVKKAERTRVIRPPLLVDKIVCRELRDPgsflliYLNEFH--SAVG 259
Cdd:cd13389   12 RKLIKEGEL-MKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNNELPLSGMKVKLPEDEE------YSNEFQiiSTKR 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119591949 260 AYTFQASGQALCRGWVDTIYNAQNQLQQLRA 290
Cdd:cd13389   85 SFTLIASSEEERDEWVKALSRAIEEHTKKQR 115

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 119591949 184 LLLEGSLRMKEGKDskmDVYCFLFTDLLLVTKavKKAERTRVIRppllvDKIVCREL-------RDPGSFLLIYLNEFHS 256
Cdd:cd13243   52 LVLEGTFRMAGAKN---ERLLFLFDKMLLITK--KREDGILQYK-----THIMCSNLmlsesipKEPLSFQVLPFDNPKL 121

                         90       100
                 ....*....|....*....|..
gi 119591949 257 avgAYTFQASGQALCRGWVDTI 278
Cdd:cd13243  122 ---QYTLQAKNQEQKRLWTQEI 140