Rho guanine nucleotide exchange factor Pleckstrin homology domain; p190RhoGEF (also called RIP2 or ARHGEF28) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. 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 346986273  774 LLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQKLIAREVANEERGMFLISASSAGPEMY 853
Cdd:cd14680     1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPPVICLQKLIVREVANEERGMFLISASSAGPEMY 80

                          90       100
                  ....*....|....*....|.
gi 346986273  854 EIHTNSKEERNNWMRRIQQAV 874
Cdd:cd14680    81 EIHTSSKEERNNWMRLIQEAV 101

protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins; p190RhoGEF, also called Rho guanine nucleotide exchange factor (RGNEF), Rho guanine nucleotide exchange factor 28 (ARHGEF28), or RIP2, is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 346986273  333 DKEKLNRHQFAPGTFSGVLQCLVCDKTLLGKESLQCSNCNANVHKGCKDAAPACTKKFQEK 393
Cdd:cd20876     1 KEKQSNGHQFVTGSFSGPTLCVVCDKPVTGKELLQCSNCTVNVHKGCKESAPPCTKKLQDK 61

Rho guanine nucleotide exchange factor Pleckstrin homology domain; p190RhoGEF (also called RIP2 or ARHGEF28) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. 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 346986273  774 LLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQKLIAREVANEERGMFLISASSAGPEMY 853
Cdd:cd14680     1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPPVICLQKLIVREVANEERGMFLISASSAGPEMY 80

                          90       100
                  ....*....|....*....|.
gi 346986273  854 EIHTNSKEERNNWMRRIQQAV 874
Cdd:cd14680    81 EIHTSSKEERNNWMRLIQEAV 101

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 346986273  537 RQDVIFELMQTEMHHIQTLFIMSEIFRKGMKEELQ-LDHSTVDKIFPCLDELLEIHRHFFYSMKERRQESCAgsdrnfVI 615
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDK------SG 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 346986273  616 DRIGDILVQQFSeenaskMKKIYGEFCCHHKEAVNLFKELQQ-NKKFQNFIKLRNSNllARRRGIPECILLVTQRITKYP 694
Cdd:cd00160    75 PRIGDVFLKLAP------FFKIYSEYCSNHPDALELLKKLKKfNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYP 146

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 346986273  695 VLVERILQYTKERTEEHKDLRKALCLIKDMIATVD 729
Cdd:cd00160   147 LLLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins; p190RhoGEF, also called Rho guanine nucleotide exchange factor (RGNEF), Rho guanine nucleotide exchange factor 28 (ARHGEF28), or RIP2, is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 346986273  333 DKEKLNRHQFAPGTFSGVLQCLVCDKTLLGKESLQCSNCNANVHKGCKDAAPACTKKFQEK 393
Cdd:cd20876     1 KEKQSNGHQFVTGSFSGPTLCVVCDKPVTGKELLQCSNCTVNVHKGCKESAPPCTKKLQDK 61

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 346986273    340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGCKDAAPA 385
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGsfKQGLRCSECKVKCHKKCADKVPK 48

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 346986273  511 QEFEAESWSLVVDPSFCNRQEKDVIKRQDVIFELMQTEMHHIQTLFIMSEIFRKGMkEELQLDHSTVDK-----IFPCLD 585
Cdd:COG5422   459 FDEEKNLWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPL-EESNIIPENARRnfikhVFANIN 537

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 346986273  586 ELLEIHRHFFYSMKERRQESCagsdrnfVIDRIGDIlVQQFSEENASKMKKIYGEfcchhKEAVNLF-KELQQNKKFQNF 664
Cdd:COG5422   538 EIYAVNSKLLKALTNRQCLSP-------IVNGIADI-FLDYVPKFEPFIKYGASQ-----PYAKYEFeREKSVNPNFARF 604

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 346986273  665 IKLRNSNLLARRRGIPECILLVTQRITKYPVLVERILQYTKERTEEHKDLRKALCLIKDMIATVDLkvnEYEKNQKWLEI 744
Cdd:COG5422   605 DHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNF---ESGKAENRGDL 681

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 346986273  745 LnkiENKTYTKLKNGHVfrKQALMSEERTLLYDGLV 780
Cdd:COG5422   682 F---HLNQQLLFKPEYV--NLGLNDEYRKIIFKGVL 712

Rho guanine nucleotide exchange factor Pleckstrin homology domain; p190RhoGEF (also called RIP2 or ARHGEF28) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. 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 346986273  774 LLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQKLIAREVANEERGMFLISASSAGPEMY 853
Cdd:cd14680     1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPPVICLQKLIVREVANEERGMFLISASSAGPEMY 80

                          90       100
                  ....*....|....*....|.
gi 346986273  854 EIHTNSKEERNNWMRRIQQAV 874
Cdd:cd14680    81 EIHTSSKEERNNWMRLIQEAV 101

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 346986273    540 VIFELMQTEMHHIQTLFIMSEIFRKGMKEELQ-LDHSTVDKIFPCLDELLEIHRHFFYSMKERRQEScagsdrNFVIDRI 618
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEERIEEW------DDSVERI 74

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 346986273    619 GDILVQQfseenaSKMKKIYGEFCCHHKEAVNLFKELQQNKKFQNFIKLRNSNLLARRRGIPECILLVTQRITKYPVLVE 698
Cdd:smart00325   75 GDVFLKL------EEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|.
gi 346986273    699 RILQYTKERTEEHKDLRKALCLIKDMIATVD 729
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVN 179

Rho guanine nucleotide exchange factor 2 Pleckstrin homology (PH) domain; ARHGEF2, also called GEF-H1, acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. It is thought to play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. ARHGEF2 contains a C1 domain followed by Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. 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 346986273  772 RTLLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDqKPSVISLQKLIAREVANEERGMFLISAssAGPE 851
Cdd:cd13393     2 RKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLD-KPAVISLQNLIVRDIANQEKGMFLISA--APPE 78

                          90       100
                  ....*....|....*....|....*...
gi 346986273  852 MYEIHTNSKEERNNWMRRIQQAVESCPE 879
Cdd:cd13393    79 MYEVHAASRDDRNTWMRLIQQTVKTCPS 106

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 346986273   540 VIFELMQTEMHHIQTLFIMSEIFRKGMKEELQLDHSTVDKIFPCLDELLEIHRHFFysMKERRQEscagsdrNFVIDRIG 619
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKE-------WISIQRIG 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 346986273   620 DILVQQFSeenaskMKKIYGEFCCHHKEAVNLFKELQQ-NKKFQNFIKLRNSNLLARRRGIPECILLVTQRITKYPVLVE 698
Cdd:pfam00621   72 DIFLKFAP------GFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 346986273   699 RILQYTKERTEEHKDLRKALCLIKDMIATVD 729
Cdd:pfam00621  146 ELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176

PH domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 346986273   756 LKNGHVFRKQALMseERTLLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAA-------VDQK--PSVISLQ 826
Cdd:pfam17838    1 HPLGEEFKKLDLT--TRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLAClstgsenVDQKtqSPIISLK 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 346986273   827 KLIAREVANEERGMFLISASSAGPEMYEIHTNSKEERNNWMRRIQQAVE 875
Cdd:pfam17838   79 KLIVREVATDKKAFFLISTSPSDPQMYELHASTKSERNTWTKLIQDAIE 127

rho guanine nucleotide exchange factor; RhoGEFs belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. The members here all contain Dbl homology (DH)-PH domains. In addition some members contain N-terminal C1 (Protein kinase C conserved region 1) domains, PDZ (also called DHR/Dlg homologous regions) domains, ANK (ankyrin) domains, and RGS (Regulator of G-protein signalling) domains or C-terminal ATP-synthase B subunit. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. RhoGEF2/Rho guanine nucleotide exchange factor 2, p114RhoGEF/p114 Rho guanine nucleotide exchange factor, p115RhoGEF, p190RhoGEF, PRG/PDZ Rho guanine nucleotide exchange factor, RhoGEF 11, RhoGEF 12, RhoGEF 18, AKAP13/A-kinase anchoring protein 13, and LARG/Leukemia-associated Rho guanine nucleotide exchange factor are included in this CD. 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 346986273  774 LLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQKLIAREVANEERGMFLISASSAG-PEM 852
Cdd:cd15789     1 LKFEGTAWLKQARGKTKDVLVVVLTDVLFFLQEKDQKYVFVSPDNKAGVVSLQKLLVREKAGQEKRMFLISASPDGmPEM 80

                          90       100
                  ....*....|....*....|..
gi 346986273  853 YEIHTNSKEERNNWMRRIQQAV 874
Cdd:cd15789    81 YELKVQKPKDKNTWIQTIRQAV 102

protein kinase C conserved region 1 (C1 domain) found in A-kinase anchor protein 13 (AKAP-13) and similar proteins; AKAP-13, also called AKAP-Lbc, breast cancer nuclear receptor-binding auxiliary protein (Brx-1), guanine nucleotide exchange factor Lbc, human thyroid-anchoring protein 31, lymphoid blast crisis oncogene (LBC oncogene), non-oncogenic Rho GTPase-specific GTP exchange factor, protein kinase A-anchoring protein 13 (PRKA13), or p47, is a scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors (GPCRs). It activates RhoA in response to GPCR signaling via its function as a Rho guanine nucleotide exchange factor. It may also activate other Rho family members. AKAP-13 plays a role in cell growth, cell development and actin fiber formation. Its Rho-GEF activity is regulated by protein kinase A (PKA), through binding and phosphorylation. Alternative splicing of this gene in humans has at least 3 transcript variants encoding different isoforms (i.e. proto-/onco-Lymphoid blast crisis, Lbc and breast cancer nuclear receptor-binding auxiliary protein, and Brx) that contain a C1 domain followed by a dbl oncogene homology (DH) domain and a PH domain which are required for full transforming activity. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 346986273  333 DKEKLNRHQFAPGTFSGVLQCLVCDKTLLGKESLQCSNCNANVHKGCKDAAPACTK 388
Cdd:cd20878     1 DKKTLNGHVFSPVSSVGPTQCYHCSKPLNTKDAFLCANCNVQVHKGCRESLPVCAK 56

protein kinase C conserved region 1 (C1 domain) found in Rho guanine nucleotide exchange factor 2 (ARHGEF2) and similar proteins; ARHGEF2, also called guanine nucleotide exchange factor H1 (GEF-H1), microtubule-regulated Rho-GEF, or proliferating cell nucleolar antigen p40, acts as guanine nucleotide exchange factor (GEF) that activates Rho-GTPases by promoting the exchange of GDP for GTP. It is thought to play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. ARHGEF2 may be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. It contains a C1 domain followed by Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 346986273  338 NRHQFAPGTFSGVLQCLVCDKTLLGKESLQCSNCNANVHKGCKDAAPACTKKFQEK 393
Cdd:cd20877     4 NGHLFTTITVSGTTMCSACNKSITAKEALICPTCNVTIHNRCKDTLPNCTKVKQKQ 59

PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. 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 346986273  772 RTLLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIF--------AAVDQKPS---VISLQKLIAREVANEERGM 840
Cdd:cd13391    26 RRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLkchsktavGSSDSKQTfspVLKLNSVLIRSVATDKRAL 105

                          90       100       110
                  ....*....|....*....|....*....|....
gi 346986273  841 FLISASSAGPEMYEIHTNSKEERNNWMRRIQQAV 874
Cdd:cd13391   106 FIICTSKLGPQIYELVALTSSEKNTWMELLEEAV 139

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 346986273   340 HQFAPGTFSGVLQCLVCDKTLLGKES--LQCSNCNANVHKGCKDAAPAC 386
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKqgLKCSWCKLNVHKRCHEKVPPE 49

protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*....
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGCKDAAPAC 386
Cdd:cd20810     3 HSFELTTFKEPTTCSVCKKLLKGlfFQGYKCSVCGAAVHKECIAKVKRC 51

protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) family; MRCK is thought to be a coincidence detector of signaling by the small GTPase Cdc42 and phosphoinositides. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCK has been shown to promote cytoskeletal reorganization, which affects many biological processes. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. MRCK consists of a serine/threonine kinase domain, a cysteine rich (C1) region, a PH domain and a p21 binding motif. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*...
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGCKDAAPA 385
Cdd:cd20809     1 HKFIVRTFSTPTKCNHCTSLMVGlvRQGLVCEVCGYACHVSCADKAPQ 48

protein kinase C conserved region 1 (C1 domain) found in Drosophila melanogaster GM13116p and similar proteins; This group contains uncharacterized proteins including Drosophila melanogaster GM13116p and Caenorhabditis elegans hypothetical protein R11G1.4, both of which contain C2 (a calcium-binding domain) and C1 domains. This model describes the C1 domain, a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*
gi 346986273  338 NRHQFAPGTFSGVLQCLVCDKTL---LGKESLQCSNCNANVHKGC 379
Cdd:cd20831     4 NDHTFVATHFKGGPSCAVCNKLIpgrFGKQGYQCRDCGLICHKRC 48

protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and similar proteins; MgcRacGAP, also called Rac GTPase-activating protein 1 (RACGAP1) or protein CYK4, plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling; and ii) after phosphorylation by aurora B, MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain an N-terminal C1 domain, and a C-terminal RhoGAP domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*.
gi 346986273  353 CLVCDKTL-LGKESLQCSNCNANVHKGCKDAAP-AC 386
Cdd:cd20821    16 CVVCGKRIkFGKKALKCKDCRVVCHPDCKDKLPlPC 51

second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|..
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGC 379
Cdd:cd20798     2 HTLAEHNYKKPTVCKVCDKLLVGlvRQGLKCRDCGVNVHKKC 43

second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGC-KDAAPAC 386
Cdd:cd20830     1 HRFVEQSFSTLQWCDKCGKFLFGlvHQGLQCQDCGLVCHRTCaATGLPKC 50

second protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta (DAG kinase delta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase delta, also called 130 kDa diacylglycerol kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. DAG kinase delta contains two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*...
gi 346986273  340 HQFAPGTFSGVLQCLVCDKT---LLGKESLQCSNCNANVHKGCKDAAP 384
Cdd:cd20893     6 HQWLEGNLPVSAKCTVCDKTcgsVLRLQDWRCLWCKAMVHTSCKELLL 53

first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*.
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGCKDAA 383
Cdd:cd20797     4 HVVEVEQYMTPTFCDYCGEMLTGlmKQGVKCKNCRCNFHKRCANAP 49

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 (RASGRP2) and similar proteins; RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. It may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is also involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGCKD 381
Cdd:cd20861     4 HNFAERTFLRPVACRHCKNLILGiyKQGLKCRACGVNCHKQCKD 47

protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 346986273  338 NRHQFAPGTFSGVLQCLVCDKTLLGK--ESLQCSNCNANVHKGCKDAAPAC 386
Cdd:cd20868     4 NHHNFQMYTFDKTTNCKACKMLLRGTfyQGYYCSKCGAGAHKECLEVIPPC 54

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLG--KESLQCSNCNANVHKGC-KDAAPAC 386
Cdd:cd20838     3 HRFSVHNYKRPTFCDHCGSLLYGlyKQGLQCKVCKMNVHKRCqKNVANNC 52

PH domain; PH stands for pleckstrin homology.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 346986273   822 VISLQKLIAREVANEERG----MF-LISASSAGPEMYEIHTNSKEERNNWMRRIQQAVE 875
Cdd:pfam00169   47 SISLSGCEVVEVVASDSPkrkfCFeLRTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105

protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated Fibrosarcoma) kinase family; Raf kinases are serine/threonine kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. They act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                  ....*....|....*....|....*....|....*....|....*.
gi 346986273  340 HQFAPGTFSGVLQCLVCDKTLLgkESLQCSNCNANVHKGCKDAAPA 385
Cdd:cd20811     3 HNFVRKTFFTLAFCDVCRKLLF--QGFRCQTCGFKFHQRCSDQVPA 46