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 815890885  253 EVVEDAIDTMTCVAWYINDMKRRHEHAVRLQEIQSLLINWKGPDLTTYGELVLEGTFRVHRVRNERTFFLFDKTLLITKK 332
Cdd:cd13243     2 SVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITKK 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 815890885  333 RGDH-FVYKGNIPCSSLMLIES-TRDSLCFTVTHYKHSKQQYSIQAKTVEEKRNWTHHIKRLILEN 396
Cdd:cd13243    82 REDGiLQYKTHIMCSNLMLSESiPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

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 815890885  253 EVVEDAIDTMTCVAWYINDMKRRHEHAVRLQEIQSLLINWKGPDLTTYGELVLEGTFRVHRVRNERTFFLFDKTLLITKK 332
Cdd:cd13243     2 SVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITKK 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 815890885  333 RGDH-FVYKGNIPCSSLMLIES-TRDSLCFTVTHYKHSKQQYSIQAKTVEEKRNWTHHIKRLILEN 396
Cdd:cd13243    82 REDGiLQYKTHIMCSNLMLSESiPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

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 815890885     97 VVREIVETERMYVQDLRSIVEDYLLKIIDTPGLLKPEQVSALFGNIENIYALNSQLLRDLDSC----NSDPVAVASCFVE 172
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERieewDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885    173 RSQEFDIYTQYCNNYPNSVAALTECMRDKQQAKFFRDRQELLQH-SLPLGSYLLKPVQRILKYHLLLQEIAKHFDEEEDG 251
Cdd:smart00325   81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                           170       180
                    ....*....|....*....|
gi 815890885    252 FEVVEDAIDTMTCVAWYIND 271
Cdd:smart00325  161 REDLKKALKAIKELANQVNE 180

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885   97 VVREIVETERMYVQDLrSIVEDYLLKIIDT----PGLLKPEQVSALFGNIENIYALNSQLLRDL-DSCNSDPVA--VASC 169
Cdd:COG5422   488 AIYEVIYTERDFVKDL-EYLRDTWIKPLEEsniiPENARRNFIKHVFANINEIYAVNSKLLKALtNRQCLSPIVngIADI 566

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885  170 FVERSQEFDIYTQYCNNYPnsvAALTECMRDKQ-QAKFFR--DRQELLQHSLPLG--SYLLKPVQRILKYHLLLQEIAKH 244
Cdd:COG5422   567 FLDYVPKFEPFIKYGASQP---YAKYEFEREKSvNPNFARfdHEVERLDESRKLEldGYLTKPTTRLARYPLLLEEVLKF 643

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885  245 FDEEEDGFEVVEDAIDT----MTCVAWYINDMKRRHEHavrLQEIQSLLINWKGPDLT---TYGELVLEGTFRVH----- 312
Cdd:COG5422   644 TDPDNPDTEDIPKVIDMlrefLSRLNFESGKAENRGDL---FHLNQQLLFKPEYVNLGlndEYRKIIFKGVLKRKakskt 720

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 815890885  313 --RVRNERTFFLFDKTLLITK-----KRGDHFVYKGNIPCSSLML 350
Cdd:COG5422   721 dgSLRGDIQFFLLDNMLLFCKakavnKWRQHKVFQRPIPLELLFI 765

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885   317 ERTFFLFDKTLLITK--KRGDHFVYKGNIPCSSLMLIESTRDS-----LCFTV-THYKHSKQQYSIQAKTVEEKRNWTHH 388
Cdd:pfam00169   20 KRYFVLFDGSLLYYKddKSGKSKEPKGSISLSGCEVVEVVASDspkrkFCFELrTGERTGKRTYLLQAESEEERKDWIKA 99

                   ....*
gi 815890885   389 IKRLI 393
Cdd:pfam00169  100 IQSAI 104

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 815890885  253 EVVEDAIDTMTCVAWYINDMKRRHEHAVRLQEIQSLLINWKGPDLTTYGELVLEGTFRVHRVRNERTFFLFDKTLLITKK 332
Cdd:cd13243     2 SVVEEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLDGWEGPELTTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITKK 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 815890885  333 RGDH-FVYKGNIPCSSLMLIES-TRDSLCFTVTHYKHSKQQYSIQAKTVEEKRNWTHHIKRLILEN 396
Cdd:cd13243    82 REDGiLQYKTHIMCSNLMLSESiPKEPLSFQVLPFDNPKLQYTLQAKNQEQKRLWTQEIKRLILEN 147

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 815890885     97 VVREIVETERMYVQDLRSIVEDYLLKIIDTPGLLKPEQVSALFGNIENIYALNSQLLRDLDSC----NSDPVAVASCFVE 172
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERieewDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885    173 RSQEFDIYTQYCNNYPNSVAALTECMRDKQQAKFFRDRQELLQH-SLPLGSYLLKPVQRILKYHLLLQEIAKHFDEEEDG 251
Cdd:smart00325   81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHED 160

                           170       180
                    ....*....|....*....|
gi 815890885    252 FEVVEDAIDTMTCVAWYIND 271
Cdd:smart00325  161 REDLKKALKAIKELANQVNE 180

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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 815890885  277 EHAVRLQEIQSLLINWKGPDLT-TYGELVLEGtfRVHRVR----NERTFFLFDKTLLITKK---RGDHFVYKGNIPcSSL 348
Cdd:cd01224     2 ENLEKLAAWQSTVEGWEGEDLSdRSSELIHSG--ELTKISagraQERTFFLFDHQLVYCKKdllRRKNYIYKGRID-TDN 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 815890885  349 MLIESTRDSLCF----TVTH----YKHSKQQ-YSIQAKTVEEKRNW 385
Cdd:cd01224    79 MEIEDLPDGKDDesgvTVKNawkiYNASKNKwYVLCAKSAEEKQRW 124

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885   97 VVREIVETERMYVQDLrSIVEDYLLKIIDT----PGLLKPEQVSALFGNIENIYALNSQLLRDL-DSCNSDPVA--VASC 169
Cdd:COG5422   488 AIYEVIYTERDFVKDL-EYLRDTWIKPLEEsniiPENARRNFIKHVFANINEIYAVNSKLLKALtNRQCLSPIVngIADI 566

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885  170 FVERSQEFDIYTQYCNNYPnsvAALTECMRDKQ-QAKFFR--DRQELLQHSLPLG--SYLLKPVQRILKYHLLLQEIAKH 244
Cdd:COG5422   567 FLDYVPKFEPFIKYGASQP---YAKYEFEREKSvNPNFARfdHEVERLDESRKLEldGYLTKPTTRLARYPLLLEEVLKF 643

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885  245 FDEEEDGFEVVEDAIDT----MTCVAWYINDMKRRHEHavrLQEIQSLLINWKGPDLT---TYGELVLEGTFRVH----- 312
Cdd:COG5422   644 TDPDNPDTEDIPKVIDMlrefLSRLNFESGKAENRGDL---FHLNQQLLFKPEYVNLGlndEYRKIIFKGVLKRKakskt 720

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 815890885  313 --RVRNERTFFLFDKTLLITK-----KRGDHFVYKGNIPCSSLML 350
Cdd:COG5422   721 dgSLRGDIQFFLLDNMLLFCKakavnKWRQHKVFQRPIPLELLFI 765

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 815890885  301 GELVLEGTFRVHRVRnERTFFLFDKTLLITKKRGD-HFVYKGNIPCSSLMLIESTRDSL---CFTVTHYKHskQQYSIQA 376
Cdd:cd00821     3 GYLLKRGGGGLKSWK-KRWFVLFEGVLLYYKSKKDsSYKPKGSIPLSGILEVEEVSPKErphCFELVTPDG--RTYYLQA 79

                          90
                  ....*....|...
gi 815890885  377 KTVEEKRNWTHHI 389
Cdd:cd00821    80 DSEEERQEWLKAL 92

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 815890885  286 QSLLINWKGPDLTTYGELVLEGTFRV-----HRVRNeRTFFLFDKTLLITKK-RGDHFVYKGNIPCSS------LMLIES 353
Cdd:cd01223     2 IQDLIENLNESLADYGRLQIDGELKIkshedQKKKD-RYAFLFDKVLLICKSlRGDQYEYKEIINLSEyrieddPSRRTL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 815890885  354 TRD---SLCFTVTHyKHSKQQYSIQAKTVEEKRNW 385
Cdd:cd01223    81 KRDkrwSYQFLLVH-KQGKTAYTLYAKTEELKKKW 114

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 815890885   317 ERTFFLFDKTLLITK--KRGDHFVYKGNIPCSSLMLIESTRDS-----LCFTV-THYKHSKQQYSIQAKTVEEKRNWTHH 388
Cdd:pfam00169   20 KRYFVLFDGSLLYYKddKSGKSKEPKGSISLSGCEVVEVVASDspkrkFCFELrTGERTGKRTYLLQAESEEERKDWIKA 99

                   ....*
gi 815890885   389 IKRLI 393
Cdd:pfam00169  100 IQSAI 104