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 354459394 643 KIKPFPLVSSSRWLVKRGELTAYVEDTV--LFSRRTSKQQVYFFLFNDVLIITKKKSEESYNVNDYSLRDQLLVESCDNE 720
Cdd:cd01221    1 KIKAFPLISSSRWLVKRGELTELVEDGGslTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVEDP 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 354459394 721 ELNSSPGknsstmlysrqssASHLFTLTVLSNHANEKVEMLLGAETQSERARWITALGHSS 781
Cdd:cd01221   81 LQLPQPL-------------GKNLFLLTLLENHEGKTVELLLSAESESDRERWLSALSPPK 128

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394   18 WRRRSIPQ---PHQVLGRSKPRPQSYQSPNGLLITDFPVEDGGTLLAAQIPAqVPTASDSRTVHRSPLLLGAQRRAVANG 94
Cdd:PHA03247 2683 PRRRAARPtvgSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPA-LPAAPAPPAVPAGPATPGGPARPARPP 2761

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394   95 GTASPEY------RAASPRLRRPKSPKLPKAVpgGSPKSPANGAVTLPAPPPPPVLRPPRTPNAPAPCTPeedlTGLTAS 168
Cdd:PHA03247 2762 TTAGPPApappaaPAAGPPRRLTRPAVASLSE--SRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLP----PPTSAQ 2835

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 354459394  169 PVPSPTANGLAANNDSPGSGSQSGR--KAKDPERglfPGPQKSSSEQKLPLQRLP 221
Cdd:PHA03247 2836 PTAPPPPPGPPPPSLPLGGSVAPGGdvRRRPPSR---SPAAKPAAPARPPVRRLA 2887

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 354459394 643 KIKPFPLVSSSRWLVKRGELTAYVEDTV--LFSRRTSKQQVYFFLFNDVLIITKKKSEESYNVNDYSLRDQLLVESCDNE 720
Cdd:cd01221    1 KIKAFPLISSSRWLVKRGELTELVEDGGslTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVEDP 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 354459394 721 ELNSSPGknsstmlysrqssASHLFTLTVLSNHANEKVEMLLGAETQSERARWITALGHSS 781
Cdd:cd01221   81 LQLPQPL-------------GKNLFLLTLLENHEGKTVELLLSAESESDRERWLSALSPPK 128

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 354459394   443 AIFEVISSEHSYLLSLEILIRMF-KNSKELSDTMTKTERHHLFSNITDVCEASKKFFIELEARHQN-NIFIDDISDIVEK 520
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFlKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEwDDSVERIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394   521 HtASTFDPYVKYCTNEVYQQRTLQKLlATNPSFKEVLSRIESHEDCRNLPMISFLILPMQRVTRLPLLMDTICQKTPKDS 600
Cdd:smart00325  81 L-EEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158

                          170       180
                   ....*....|....*....|..
gi 354459394   601 PKYEVCKRALKEVSKLVRLCNE 622
Cdd:smart00325 159 EDREDLKKALKAIKELANQVNE 180

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  427 KGLSQTVSQEERKRQEAIFEVISSEHSYLLSLEIL----IRMFKNSKELSDTMTKTERHHLFSNITDVCEASKKFFIELE 502
Cdd:COG5422   472 KEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLrdtwIKPLEESNIIPENARRNFIKHVFANINEIYAVNSKLLKALT 551

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  503 ARHQNNIFIDDISDIVEKHTaSTFDPYVKYCTNEVYQQRTLQKLLATNPSFKEVLSRIESHEDCRNLPMISFLILPMQRV 582
Cdd:COG5422   552 NRQCLSPIVNGIADIFLDYV-PKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRL 630

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  583 TRLPLLMDTICQKTPKDSPKYEVCKRALKEVSKLVRLCNEGARKMERTEMMYTINSQLEFKIKPFP--LVSSSRWLVKRG 660
Cdd:COG5422   631 ARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVNlgLNDEYRKIIFKG 710

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  661 ELTayvEDTVLFSRRTSKQQVYFFLFNDVLIITKKKSEESYNVNDYSLRD--QLLVESC---DNEELNSSPGKNSSTMLY 735
Cdd:COG5422   711 VLK---RKAKSKTDGSLRGDIQFFLLDNMLLFCKAKAVNKWRQHKVFQRPipLELLFISpdeDSPDRAEYLKPAPSADVL 787

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|
gi 354459394  736 SRQSSASHLFTLTVLSNHAN-EKVEMLLGAETQSERARWI 774
Cdd:COG5422   788 DPAYNTKPPKNAYGFELYGNgQRYQITLYAETHAGRDTWL 827

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  655 WLVKRGEltayvedtvlfSRRTSKQQVYFFLFNDVLIITKKKSEESynvndyslrdqllvescDNEELNSSPGKNSSTML 734
Cdd:pfam00169   6 WLLKKGG-----------GKKKSWKKRYFVLFDGSLLYYKDDKSGK-----------------SKEPKGSISLSGCEVVE 57

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 354459394  735 YSRQSSASHLFTLTVLSNHANEKVEMLLGAETQSERARWITAL 777
Cdd:pfam00169  58 VVASDSPKRKFCFELRTGERTGKRTYLLQAESEEERKDWIKAI 100

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 354459394 643 KIKPFPLVSSSRWLVKRGELTAYVEDTV--LFSRRTSKQQVYFFLFNDVLIITKKKSEESYNVNDYSLRDQLLVESCDNE 720
Cdd:cd01221    1 KIKAFPLISSSRWLVKRGELTELVEDGGslTFRKKFSKTPVYLFLFNDLLLITKKKSEERYLVLDYAPRNLVQVEEVEDP 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 354459394 721 ELNSSPGknsstmlysrqssASHLFTLTVLSNHANEKVEMLLGAETQSERARWITALGHSS 781
Cdd:cd01221   81 LQLPQPL-------------GKNLFLLTLLENHEGKTVELLLSAESESDRERWLSALSPPK 128

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 354459394   443 AIFEVISSEHSYLLSLEILIRMF-KNSKELSDTMTKTERHHLFSNITDVCEASKKFFIELEARHQN-NIFIDDISDIVEK 520
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFlKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEwDDSVERIGDVFLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394   521 HtASTFDPYVKYCTNEVYQQRTLQKLlATNPSFKEVLSRIESHEDCRNLPMISFLILPMQRVTRLPLLMDTICQKTPKDS 600
Cdd:smart00325  81 L-EEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158

                          170       180
                   ....*....|....*....|..
gi 354459394   601 PKYEVCKRALKEVSKLVRLCNE 622
Cdd:smart00325 159 EDREDLKKALKAIKELANQVNE 180

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  427 KGLSQTVSQEERKRQEAIFEVISSEHSYLLSLEIL----IRMFKNSKELSDTMTKTERHHLFSNITDVCEASKKFFIELE 502
Cdd:COG5422   472 KEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLrdtwIKPLEESNIIPENARRNFIKHVFANINEIYAVNSKLLKALT 551

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  503 ARHQNNIFIDDISDIVEKHTaSTFDPYVKYCTNEVYQQRTLQKLLATNPSFKEVLSRIESHEDCRNLPMISFLILPMQRV 582
Cdd:COG5422   552 NRQCLSPIVNGIADIFLDYV-PKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRL 630

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  583 TRLPLLMDTICQKTPKDSPKYEVCKRALKEVSKLVRLCNEGARKMERTEMMYTINSQLEFKIKPFP--LVSSSRWLVKRG 660
Cdd:COG5422   631 ARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVNlgLNDEYRKIIFKG 710

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394  661 ELTayvEDTVLFSRRTSKQQVYFFLFNDVLIITKKKSEESYNVNDYSLRD--QLLVESC---DNEELNSSPGKNSSTMLY 735
Cdd:COG5422   711 VLK---RKAKSKTDGSLRGDIQFFLLDNMLLFCKAKAVNKWRQHKVFQRPipLELLFISpdeDSPDRAEYLKPAPSADVL 787

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|
gi 354459394  736 SRQSSASHLFTLTVLSNHAN-EKVEMLLGAETQSERARWI 774
Cdd:COG5422   788 DPAYNTKPPKNAYGFELYGNgQRYQITLYAETHAGRDTWL 827

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 354459394 655 WLVKRGELTayvedtvlfsrRTSKQQVYFFLFNDVLIITKKKSEESYN-VNDYSLRDQLLVESCDNEELNsspgknsstm 733
Cdd:cd00821    4 YLLKRGGGG-----------LKSWKKRWFVLFEGVLLYYKSKKDSSYKpKGSIPLSGILEVEEVSPKERP---------- 62

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 354459394 734 lysrqssasHLFTLTvlsnHANEKVeMLLGAETQSERARWITAL 777
Cdd:cd00821   63 ---------HCFELV----TPDGRT-YYLQADSEEERQEWLKAL 92

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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 354459394 670 VLFSRRTSKQQVYFFLFNDVLIITKKKSEESYNVNdYSLR-DQLLVESCDNE--ELNSSPGK 728
Cdd:cd13319    9 VQLTRGLQTQERHLFLFSDVLVVAKPKSKNSFKLK-HKIRlSELWLASCVDEvcEGSKSADK 69

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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 354459394 628 ERTEMMYTINSqlEFKIKPFPLVSSSRWLVKRGELTAyvedtvlFSRRTSKQQvYFFLFNDVLI-----ITKKKseesyn 702
Cdd:cd01218    4 ANRRRIAAVES--CFGGSGQPLVKPGRVLVGEGVLTK-------VCRKKPKPR-QFFLFNDILVygsivINKKK------ 67

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 354459394 703 vndYSLRDQLLVESCDNEEL-NSSPGKNSSTMLYSRQSsashlFTLTvlsnhanekvemllgAETQSERARWITAL 777
Cdd:cd01218   68 ---YNKQRIIPLEDVKIEDLeDTGELKNGWQIISPKKS-----FVVY---------------AATATEKSEWMDHI 120

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. 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.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. 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 kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 354459394 677 SKQQVYFFLFNDVLIITKKKSEESY------NVNDYSLRDqllvescdneelnsspgkNSSTMLYSRQSSASHLFTLTvl 750
Cdd:cd01223   34 KKKDRYAFLFDKVLLICKSLRGDQYeykeiiNLSEYRIED------------------DPSRRTLKRDKRWSYQFLLV-- 93

                         90       100
                 ....*....|....*....|....*..
gi 354459394 751 snHANEKVEMLLGAETQSERARWITAL 777
Cdd:cd01223   94 --HKQGKTAYTLYAKTEELKKKWMEAI 118

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 354459394 603 YEVCKRALKEVSKLVRLCNEGARKMERTEMMYTINSQLefkikpfplvssSRWLVKrgELTAYvEDTVLFSR---RTSKQ 679
Cdd:cd13243    1 RSVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLL------------DGWEGP--ELTTY-GDLVLEGTfrmAGAKN 65

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 354459394 680 QVYFFLFNDVLIITKKKSEESYNVNDYSLRDQL-LVESCDNEEL 722
Cdd:cd13243   66 ERLLFLFDKMLLITKKREDGILQYKTHIMCSNLmLSESIPKEPL 109