p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 24654956 525 LQDFDGEITAQGSLLMQGPMNCVVDAA---QKHRELQVFLFQQIIIFADIEKTKNQYASPIFKYRSHIQLNHMQMKELGD 601
Cdd:cd13241   4 LQGFDGKITAQGKLLLQGTLLVSEPSAgllQKGKERRVFLFEQIIIFSEILGKKTQFSNPGYIYKNHIKVNKMSLEENVD 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24654956 602 ---CRFQIRSTDPKIPEMTIICQAASQENYAGWRDMLNKILQQQNDLIFMLSNPLST 655
Cdd:cd13241  84 gdpLRFALKSRDPNNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 24654956 525 LQDFDGEITAQGSLLMQGPMNCVVDAA---QKHRELQVFLFQQIIIFADIEKTKNQYASPIFKYRSHIQLNHMQMKELGD 601
Cdd:cd13241   4 LQGFDGKITAQGKLLLQGTLLVSEPSAgllQKGKERRVFLFEQIIIFSEILGKKTQFSNPGYIYKNHIKVNKMSLEENVD 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24654956 602 ---CRFQIRSTDPKIPEMTIICQAASQENYAGWRDMLNKILQQQNDLIFMLSNPLST 655
Cdd:cd13241  84 gdpLRFALKSRDPNNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140

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 24654956 337 RQCVFAELMSTEEAYVQDLHEIVNGYMTEINNtnSDIPMPEDlkggKMKLVFNNIKDIYEWHRDFFLR---ALRNCQKSP 413
Cdd:cd00160   1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDK--ELLPLSPE----EVELLFGNIEEIYEFHRIFLKSleeRVEEWDKSG 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654956 414 ADLGPLIKRSATKFALYYTYCSNKPLSEYIVSAHYQ---YFDSIRQKLG---HRLDLSNLIIKPVQRITKYELLIKEIIK 487
Cdd:cd00160  75 PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnkFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLK 154

                       170       180
                ....*....|....*....|....*....
gi 24654956 488 ATEGAglYKEVPMLQEAYQQMKVVVKTVN 516
Cdd:cd00160 155 HTPDG--HEDREDLKKALEAIKEVASQVN 181

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654956  336 KRQCVFAELMSTEEAYVQDLHEIVNGYMTEINNTNSdipMPEDLKGGKMKLVFNNIKDIYEWHRDFfLRALRNCQK-SPA 414
Cdd:COG5422  484 KRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNI---IPENARRNFIKHVFANINEIYAVNSKL-LKALTNRQClSPI 559

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654956  415 --DLGPLIKRSATKFALYYTYCSNKPLSEYIV----SAHYQYF----DSIRQKLGHRLDLSNLIIKPVQRITKYELLIKE 484
Cdd:COG5422  560 vnGIADIFLDYVPKFEPFIKYGASQPYAKYEFerekSVNPNFArfdhEVERLDESRKLELDGYLTKPTTRLARYPLLLEE 639

                        170       180
                 ....*....|....*....|...
gi 24654956  485 IIKAT-EGAGLYKEVPMLQEAYQ 506
Cdd:COG5422  640 VLKFTdPDNPDTEDIPKVIDMLR 662

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 24654956 525 LQDFDGEITAQGSLLMQGPMNCVVDAA---QKHRELQVFLFQQIIIFADIEKTKNQYASPIFKYRSHIQLNHMQMKELGD 601
Cdd:cd13241   4 LQGFDGKITAQGKLLLQGTLLVSEPSAgllQKGKERRVFLFEQIIIFSEILGKKTQFSNPGYIYKNHIKVNKMSLEENVD 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24654956 602 ---CRFQIRSTDPKIPEMTIICQAASQENYAGWRDMLNKILQQQNDLIFMLSNPLST 655
Cdd:cd13241  84 gdpLRFALKSRDPNNPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140

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 24654956 337 RQCVFAELMSTEEAYVQDLHEIVNGYMTEINNtnSDIPMPEDlkggKMKLVFNNIKDIYEWHRDFFLR---ALRNCQKSP 413
Cdd:cd00160   1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDK--ELLPLSPE----EVELLFGNIEEIYEFHRIFLKSleeRVEEWDKSG 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654956 414 ADLGPLIKRSATKFALYYTYCSNKPLSEYIVSAHYQ---YFDSIRQKLG---HRLDLSNLIIKPVQRITKYELLIKEIIK 487
Cdd:cd00160  75 PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnkFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLK 154

                       170       180
                ....*....|....*....|....*....
gi 24654956 488 ATEGAglYKEVPMLQEAYQQMKVVVKTVN 516
Cdd:cd00160 155 HTPDG--HEDREDLKKALEAIKEVASQVN 181

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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 24654956 524 SLQDFDGEITAQGSLLMQGPMncVVDAAQKHRELQVFLFQQIIIFADIEKTKNqyASPIFKYRSHIQLNHMQMKE-LGD- 601
Cdd:cd13242  15 SIRGCDVNLKEQGQLLRQDEF--LVWQGRKKCLRHVFLFEDLILFSKPKKTPG--GKDVYIYKHSIKTSDIGLTEnVGDs 90

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 24654956 602 -CRFQIRSTDPKIPEmTIICQAASQENYAGWRDMLNKILQQQ 642
Cdd:cd13242  91 gLKFEIWFRRRKARD-TYILQATSPEIKQAWTSDIAKLLWKQ 131

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654956 525 LQDFDGEITAQGSLLMQGPMNcVVDAAQ---KHRELQVFLFQQIIIFAdiEKTKNQYASPIFKYRSHIQLNHMQMKEL-- 599
Cdd:cd13240   2 LEGCDEDLDSLGEVILQDSFQ-VWDPKQlirKGRERHVFLFELCLVFS--KEVKDSNGKSKYIYKSRLMTSEIGVTEHie 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 24654956 600 GD-CRFQIRSTDPKIPEMTIICQAASQENYAGWRDMLNKILQQ 641
Cdd:cd13240  79 GDpCKFALWTGRVPTSDNKIVLKASSLEVKQTWVKKLREVIQE 121

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 24654956   535 QGSLLMQGPMNcVVDAAQKHRELQVFLFQQIIIFADIEKTKNQ 577
Cdd:pfam15411   2 FGELLLHDKLT-VGKDSDSEREYHVYLFEKILLCCKEISPKKK 43