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 568931363  683 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTKVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 761
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90       100
                  ....*....|....*....|
gi 568931363  762 YTFQASSQALCRSWVDTIYN 781
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568931363  172 KECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKAK 246
Cdd:cd17068     1 KECFTVKFDDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKAK 75

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 568931363  683 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTKVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 761
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90       100
                  ....*....|....*....|
gi 568931363  762 YTFQASSQALCRSWVDTIYN 781
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568931363  172 KECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKAK 246
Cdd:cd17068     1 KECFTVKFDDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKAK 75

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 568931363   440 AVWELLHTEVSYIRKLRVITNLFLCcllnlQESGLLCEVEAER--LFSNIPEIAKLHRGLWgsvmvpvLEKarRTRALLQ 517
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLP-----PNSKPLSESEEEIktIFSNIEEIYELHRQLL-------LEE--LLKEWIS 66

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363   518 PSDFLKGFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYVTWAEKHQQCQRLKLSDMLAKPHQRLTKYPLLLKS 597
Cdd:pfam00621   67 IQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKE 146

                          170       180       190
                   ....*....|....*....|....*....|
gi 568931363   598 VLRKT-DDPRTKEAIVTMISSVERFIHHVN 626
Cdd:pfam00621  147 LLKHTpPDHPDYEDLKKALEAIKEVAKQIN 176

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363  428 EKLTRRQCHQQEAVWELLHTEVSYIRKLRVItnlFLCCLLNLQESGLLCEVEAERL----FSNIPEIAKLHRGLwgsvmv 503
Cdd:COG5422   476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYL---RDTWIKPLEESNIIPENARRNFikhvFANINEIYAVNSKL------ 546

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363  504 pvlEKARRTRALLQPSDFLKG--FKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYVTWAEKHQQCQRLKLSDML 581
Cdd:COG5422   547 ---LKALTNRQCLSPIVNGIAdiFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYL 623

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363  582 AKPHQRLTKYPLLLKSVLRKTDDPRT-KEAIVTMISSVERFIHHVNTCMRQRQERQRLAGVVSRIDAyevvegSNDEVDk 660
Cdd:COG5422   624 TKPTTRLARYPLLLEEVLKFTDPDNPdTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLF------KPEYVN- 696

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568931363  661 llkefLHLDltapmpgtspEETRQLLLEGSLRMKE-GKDS---KMDVYCFLFTDLLLV--TKAVKKAERTKVIRPPL 731
Cdd:COG5422   697 -----LGLN----------DEYRKIIFKGVLKRKAkSKTDgslRGDIQFFLLDNMLLFckAKAVNKWRQHKVFQRPI 758

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 568931363  683 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTKVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 761
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90       100
                  ....*....|....*....|
gi 568931363  762 YTFQASSQALCRSWVDTIYN 781
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568931363  172 KECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKAK 246
Cdd:cd17068     1 KECFTVKFDDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKAK 75

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 568931363   440 AVWELLHTEVSYIRKLRVITNLFLCcllnlQESGLLCEVEAER--LFSNIPEIAKLHRGLWgsvmvpvLEKarRTRALLQ 517
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLP-----PNSKPLSESEEEIktIFSNIEEIYELHRQLL-------LEE--LLKEWIS 66

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363   518 PSDFLKGFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYVTWAEKHQQCQRLKLSDMLAKPHQRLTKYPLLLKS 597
Cdd:pfam00621   67 IQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKE 146

                          170       180       190
                   ....*....|....*....|....*....|
gi 568931363   598 VLRKT-DDPRTKEAIVTMISSVERFIHHVN 626
Cdd:pfam00621  147 LLKHTpPDHPDYEDLKKALEAIKEVAKQIN 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 568931363  684 QLLLEGSLRMKE-GKdsKMDVYCFLFTDLLLVTKaVKKAERTK-------------------------VIRPPLLVDKIV 737
Cdd:cd13245     1 QLLHEGPLTLIEsGK--TLDVYLFLFDDMLLITK-MKKNLKKKkssdsensmpsleltplikeggsytVYKQPIPLDRLC 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568931363  738 CRELrDP---------GSFLLIYLNEFHSAVGAYTFQASSQALCRSWVDTI 779
Cdd:cd13245    78 LHDV-DPneatanglkHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKL 127

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 568931363  687 LEGSLRMKEGKDSK--MDVYCFLFTDLLLVTKAVKKA--ERTKVIRPPLLVDKIVCRELRDPGSFLLIylnefHSAVGAY 762
Cdd:cd00821     1 KEGYLLKRGGGGLKswKKRWFVLFEGVLLYYKSKKDSsyKPKGSIPLSGILEVEEVSPKERPHCFELV-----TPDGRTY 75

                          90
                  ....*....|....*..
gi 568931363  763 TFQASSQALCRSWVDTI 779
Cdd:cd00821    76 YLQADSEEERQEWLKAL 92

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 568931363  683 RQLLLEGSLrMKEGKDSKMDVYCFLFTDLLLVTKAVKKAERTKVIRPPLLVDKIVCRELRDPgsflliYLNEFH--SAVG 760
Cdd:cd13389    12 RKLIKEGEL-MKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNNELPLSGMKVKLPEDEE------YSNEFQiiSTKR 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 568931363  761 AYTFQASSQALCRSWVDTIYNAQNQLQQLRA 791
Cdd:cd13389    85 SFTLIASSEEERDEWVKALSRAIEEHTKKQR 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363  428 EKLTRRQCHQQEAVWELLHTEVSYIRKLRVItnlFLCCLLNLQESGLLCEVEAERL----FSNIPEIAKLHRGLwgsvmv 503
Cdd:COG5422   476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYL---RDTWIKPLEESNIIPENARRNFikhvFANINEIYAVNSKL------ 546

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363  504 pvlEKARRTRALLQPSDFLKG--FKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYVTWAEKHQQCQRLKLSDML 581
Cdd:COG5422   547 ---LKALTNRQCLSPIVNGIAdiFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYL 623

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568931363  582 AKPHQRLTKYPLLLKSVLRKTDDPRT-KEAIVTMISSVERFIHHVNTCMRQRQERQRLAGVVSRIDAyevvegSNDEVDk 660
Cdd:COG5422   624 TKPTTRLARYPLLLEEVLKFTDPDNPdTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLF------KPEYVN- 696

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568931363  661 llkefLHLDltapmpgtspEETRQLLLEGSLRMKE-GKDS---KMDVYCFLFTDLLLV--TKAVKKAERTKVIRPPL 731
Cdd:COG5422   697 -----LGLN----------DEYRKIIFKGVLKRKAkSKTDgslRGDIQFFLLDNMLLFckAKAVNKWRQHKVFQRPI 758

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. 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
                  ....*....|....*....|....*....|....*....|
gi 568931363  683 RQLLLEGSLRMKEGKDSKmDVYCFLFTDLLLVTKAVKKAE 722
Cdd:cd13319     1 RTFLLEGPVQLTRGLQTQ-ERHLFLFSDVLVVAKPKSKNS 39

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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
                  ....*....|....*....|....*....|....*....|..
gi 568931363  681 ETRQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKavKKAE 722
Cdd:cd01221    19 ELTELVEDGGSLTFRKKFSKTPVYLFLFNDLLLITK--KKSE 58