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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836 220 KVKALPLVSWSRRLEFQGELTELGCRRGGVLFASRPRFTPLCLLLFSDLLLITQPKSGQRLQVLDYAHRSLVQAQQV--- 296
Cdd:cd01221    1 KIKAFPLISSSRWLVKRGELTELVEDGGSLTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVedp 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 767991836 297 ---PDPSGPPTFRLSLLSNHQGRPTHRLLQASSLSDMQRWLGAFPTP 340
Cdd:cd01221   81 lqlPQPLGKNLFLLTLLENHEGKTVELLLSAESESDRERWLSALSPP 127

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836 220 KVKALPLVSWSRRLEFQGELTELGCRRGGVLFASRPRFTPLCLLLFSDLLLITQPKSGQRLQVLDYAHRSLVQAQQV--- 296
Cdd:cd01221    1 KIKAFPLISSSRWLVKRGELTELVEDGGSLTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVedp 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 767991836 297 ---PDPSGPPTFRLSLLSNHQGRPTHRLLQASSLSDMQRWLGAFPTP 340
Cdd:cd01221   81 lqlPQPLGKNLFLLTLLENHEGKTVELLLSAESESDRERWLSALSPP 127

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 767991836    5 LFEVVTSEASYLRSLRLLTDTFVLSQALRDTLTPRDHHTLFSNVQRVQGVSERFLatLLSRVRSSPHISDLCDVVHAHAV 84
Cdd:pfam00621   2 IKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFAP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836   85 GpFSVYVDYVRNQQYQEETYSRLMDTNVRFSAELRRLQSLPKCERLPLPSFLLLPFQRITRLRMLLqghraggpvtlppc 164
Cdd:pfam00621  80 G-FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL-------------- 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767991836  165 pQNILRQTEEGSSRQENAQKALGAVSKIIERC 196
Cdd:pfam00621 145 -KELLKHTPPDHPDYEDLKKALEAIKEVAKQI 175

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836    2 QESLFEVVTSEASYLRSLRLLTDTFVlSQALRDTLTPRDH-----HTLFSNVQRVQGVSERFLATLLSRVRSSPHISDLC 76
Cdd:COG5422   486 QEAIYEVIYTERDFVKDLEYLRDTWI-KPLEESNIIPENArrnfiKHVFANINEIYAVNSKLLKALTNRQCLSPIVNGIA 564

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836   77 DVVHAHaVGPFSVYVDYVRNQQYQEETYSRLMDTN---VRFSAELRRLQSlpkcerlplpsflllpfqritRLRMLLQGH 153
Cdd:COG5422   565 DIFLDY-VPKFEPFIKYGASQPYAKYEFEREKSVNpnfARFDHEVERLDE---------------------SRKLELDGY 622

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836  154 RAGGPVTLPPCP---QNILRQTEEGSSRQENAQKALGAVSKIIERCSAEVGRMKQTEELIRLTQRLRFHKVKA-LPLVSW 229
Cdd:COG5422   623 LTKPTTRLARYPlllEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVnLGLNDE 702

                         250
                  ....*....|
gi 767991836  230 SRRLEFQGEL 239
Cdd:COG5422   703 YRKIIFKGVL 712

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836 220 KVKALPLVSWSRRLEFQGELTELGCRRGGVLFASRPRFTPLCLLLFSDLLLITQPKSGQRLQVLDYAHRSLVQAQQV--- 296
Cdd:cd01221    1 KIKAFPLISSSRWLVKRGELTELVEDGGSLTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVedp 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 767991836 297 ---PDPSGPPTFRLSLLSNHQGRPTHRLLQASSLSDMQRWLGAFPTP 340
Cdd:cd01221   81 lqlPQPLGKNLFLLTLLENHEGKTVELLLSAESESDRERWLSALSPP 127

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 767991836    5 LFEVVTSEASYLRSLRLLTDTFVLSQALRDTLTPRDHHTLFSNVQRVQGVSERFLatLLSRVRSSPHISDLCDVVHAHAV 84
Cdd:pfam00621   2 IKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFAP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836   85 GpFSVYVDYVRNQQYQEETYSRLMDTNVRFSAELRRLQSLPKCERLPLPSFLLLPFQRITRLRMLLqghraggpvtlppc 164
Cdd:pfam00621  80 G-FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL-------------- 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767991836  165 pQNILRQTEEGSSRQENAQKALGAVSKIIERC 196
Cdd:pfam00621 145 -KELLKHTPPDHPDYEDLKKALEAIKEVAKQI 175

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836    2 QESLFEVVTSEASYLRSLRLLTDTFVlSQALRDTLTPRDH-----HTLFSNVQRVQGVSERFLATLLSRVRSSPHISDLC 76
Cdd:COG5422   486 QEAIYEVIYTERDFVKDLEYLRDTWI-KPLEESNIIPENArrnfiKHVFANINEIYAVNSKLLKALTNRQCLSPIVNGIA 564

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836   77 DVVHAHaVGPFSVYVDYVRNQQYQEETYSRLMDTN---VRFSAELRRLQSlpkcerlplpsflllpfqritRLRMLLQGH 153
Cdd:COG5422   565 DIFLDY-VPKFEPFIKYGASQPYAKYEFEREKSVNpnfARFDHEVERLDE---------------------SRKLELDGY 622

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991836  154 RAGGPVTLPPCP---QNILRQTEEGSSRQENAQKALGAVSKIIERCSAEVGRMKQTEELIRLTQRLRFHKVKA-LPLVSW 229
Cdd:COG5422   623 LTKPTTRLARYPlllEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVnLGLNDE 702

                         250
                  ....*....|
gi 767991836  230 SRRLEFQGEL 239
Cdd:COG5422   703 YRKIIFKGVL 712