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 38373682  583 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 661
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 38373682  662 YTFQASGQALCRGWVDTIYN 681
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 38373682   74 KECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKA 147
Cdd:cd17068    1 KECFTVKFDDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKA 74

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 38373682  583 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 661
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 38373682  662 YTFQASGQALCRGWVDTIYN 681
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682  337 QQEAVWELLHTEASYIRKLRVIINLFLCCLLnlQESGLLCEVEAERLFSNIPEIAQLHRRLWASVMAPVLEKARRTRALl 416
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD--KELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRI- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682  417 qpGDFLKGFKmfgSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKhpQCQRLKLSDMLAKPHQRLTKYPLLLK 496
Cdd:cd00160   78 --GDVFLKLA---PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLK 150

                        170       180       190
                 ....*....|....*....|....*....|.
gi 38373682  497 SVLRKTEE-PRAKEAVVAMIGSVERFIHHVN 526
Cdd:cd00160  151 ELLKHTPDgHEDREDLKKALEAIKEVASQVN 181

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 38373682    340 AVWELLHTEASYIRKLRVIINLFLCcllnlQESGLLCEVEAER--LFSNIPEIAQLHRRLWasvmapvLEKARRTRALLQ 417
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLP-----PNSKPLSESEEEIktIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682    418 P-GD-FLKgfkmFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLL 495
Cdd:pfam00621   69 RiGDiFLK----FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                          170       180       190
                   ....*....|....*....|....*....|..
gi 38373682    496 KSVLRKTEEPRA-KEAVVAMIGSVERFIHHVN 526
Cdd:pfam00621  145 KELLKHTPPDHPdYEDLKKALEAIKEVAKQIN 176

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682  328 EKLTRRQCHQQEAVWELLHTEASYIRKLRVIinlFLCCLLNLQESGLLCEVEAERL----FSNIPEIAQLHRRLwasvma 403
Cdd:COG5422  476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYL---RDTWIKPLEESNIIPENARRNFikhvFANINEIYAVNSKL------ 546

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682  404 pvlEKARRTRALLQP-----GDFlkgFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLS 478
Cdd:COG5422  547 ---LKALTNRQCLSPivngiADI---FLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELD 620

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682  479 DMLAKPHQRLTKYPLLLKSVLRKTEEPRA-KEAVVAMIGSVERFIhhvnacmrqrqerqrlaavvSRIDayevVESSSDE 557
Cdd:COG5422  621 GYLTKPTTRLARYPLLLEEVLKFTDPDNPdTEDIPKVIDMLREFL--------------------SRLN----FESGKAE 676

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38373682  558 VDKLLKEFLHLDLTAPIPGASPE--ETRQLLLEGSLRMKE-GKDS---KMDVYCFLFTDLLLVTKA 617
Cdd:COG5422  677 NRGDLFHLNQQLLFKPEYVNLGLndEYRKIIFKGVLKRKAkSKTDgslRGDIQFFLLDNMLLFCKA 742

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 38373682  583 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 661
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 38373682  662 YTFQASGQALCRGWVDTIYN 681
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682  337 QQEAVWELLHTEASYIRKLRVIINLFLCCLLnlQESGLLCEVEAERLFSNIPEIAQLHRRLWASVMAPVLEKARRTRALl 416
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD--KELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRI- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682  417 qpGDFLKGFKmfgSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKhpQCQRLKLSDMLAKPHQRLTKYPLLLK 496
Cdd:cd00160   78 --GDVFLKLA---PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLK 150

                        170       180       190
                 ....*....|....*....|....*....|.
gi 38373682  497 SVLRKTEE-PRAKEAVVAMIGSVERFIHHVN 526
Cdd:cd00160  151 ELLKHTPDgHEDREDLKKALEAIKEVASQVN 181

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 38373682    340 AVWELLHTEASYIRKLRVIINLFLCcllnlQESGLLCEVEAER--LFSNIPEIAQLHRRLWasvmapvLEKARRTRALLQ 417
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLP-----PNSKPLSESEEEIktIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38373682    418 P-GD-FLKgfkmFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLL 495
Cdd:pfam00621   69 RiGDiFLK----FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                          170       180       190
                   ....*....|....*....|....*....|..
gi 38373682    496 KSVLRKTEEPRA-KEAVVAMIGSVERFIHHVN 526
Cdd:pfam00621  145 KELLKHTPPDHPdYEDLKKALEAIKEVAKQIN 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 38373682  584 QLLLEGSLRMKE-GKdsKMDVYCFLFTDLLLVTK----AVKK-----------AERTRVI---------RPPLLVDKIVC 638
Cdd:cd13245    1 QLLHEGPLTLIEsGK--TLDVYLFLFDDMLLITKmkknLKKKkssdsensmpsLELTPLIkeggsytvyKQPIPLDRLCL 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 38373682  639 RELrDP---------GSFLLIYLNEFHSAVGAYTFQASGQALCRGWVDTI 679
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 38373682  580 EETRQLLLEGSLRMKEGKDskmdVYCFLFTDLLLVTKAVKKAERT--RVIRPPLLVDKIVCRELRD-----PGSFLLIYL 652
Cdd:cd13224   15 ENSKALLCHGELRNKSGHK----LYVFLFQDILVLTRPVTRNERQsfQVYRQPIPVQELVLEDLQDgdvrmGGSFRGAFS 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 38373682  653 N----------EFH--SAVGAYTFQASGQALCRGWVDTIYNAQNQ 685
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 38373682  583 RQLLLEGSLrMKEGKDSKMDVYCFLFTDLLLVTKAVKKAERTRVIRPPLLVDKIVCRELRDPgsflliYLNEFH--SAVG 660
Cdd:cd13389   12 RKLIKEGEL-MKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNNELPLSGMKVKLPEDEE------YSNEFQiiSTKR 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 38373682  661 AYTFQASGQALCRGWVDTIYNAQNQLQQLRA 691
Cdd:cd13389   85 SFTLIASSEEERDEWVKALSRAIEEHTKKQR 115

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 38373682  583 RQLLLEGSLRMKEGKDSKmDVYCFLFTDLLLVTKAVKKAE 622
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        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 38373682  573 PIPGASPEetRQLLLEGSLRMKEGKD---------SKMDVYCFLFTDLLLVTKavKKAE 622
Cdd:cd01221    4 AFPLISSS--RWLVKRGELTELVEDGgsltfrkkfSKTPVYLFLFNDLLLITK--KKSE 58