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 1174098421 209 QQDVIYELIQTELHHVRTLKIMTRLFRTGMLEELH-LEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGstrnfv 287
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG------ 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174098421 288 iHRLGDLLISQFSgpsaeqMCKTYSEFCSRHSKALKLYKELYARDKRFQQFIRKVtrPAVLKRHGVQECILLVTQRITKY 367
Cdd:cd00160    75 -PRIGDVFLKLAP------FFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKA--ESECGRLKLESLLLKPVQRLTKY 145

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1174098421 368 PLLISRILQHSHGIEEERQDLTTALGLVKELLSNVD 403
Cdd:cd00160   146 PLLLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174098421  708 QEEALQRLVNLYGLLHGLQAAVAQQDTLMEARFPEGPERREKLCRANSRDGEAGRAGAApvapekqaTELALLQRQHALL 787
Cdd:COG4913    250 QIELLEPIRELAERYAAARERLAELEYLRAALRLWFAQRRLELLEAELEELRAELARLE--------AELERLEARLDAL 321

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1174098421  788 QEELRRCRRlgeERATEAG----SLEARLRESEQARALLEREAEEARRQLAALGQTEPLPAEAPWARR 851
Cdd:COG4913    322 REELDELEA---QIRGNGGdrleQLEREIERLERELEERERRRARLEALLAALGLPLPASAEEFAALR 386

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 1174098421 209 QQDVIYELIQTELHHVRTLKIMTRLFRTGMLEELH-LEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGstrnfv 287
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG------ 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174098421 288 iHRLGDLLISQFSgpsaeqMCKTYSEFCSRHSKALKLYKELYARDKRFQQFIRKVtrPAVLKRHGVQECILLVTQRITKY 367
Cdd:cd00160    75 -PRIGDVFLKLAP------FFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKA--ESECGRLKLESLLLKPVQRLTKY 145

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1174098421 368 PLLISRILQHSHGIEEERQDLTTALGLVKELLSNVD 403
Cdd:cd00160   146 PLLLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1174098421   8 RYTNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCTKVKQKQQK 68
Cdd:cd20877     1 RYTNGHLFTTITVSGTTMCSACNKSITAKEALICPTCNVTIHNRCKDTLPNCTKVKQKQQK 61

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 1174098421 212 VIYELIQTELHHVRTLKIMTRLFRTGMLEELHLEPGVVQGLFPCVDELSDIHTRFLsqlLERRRQAlcpgstrNFVIHRL 291
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---LEELLKE-------WISIQRI 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174098421 292 GDLLISQFSGPsaeqmcKTYSEFCSRHSKALKLYKELYARDKRFQQFIRKVTRPAVLKRHGVQECILLVTQRITKYPLLI 371
Cdd:pfam00621  71 GDIFLKFAPGF------KVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1174098421 372 SRILQHSHGIEEERQDLTTALGLVKELLSNVD 403
Cdd:pfam00621 145 KELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174098421  446 LIHDGCLLWKTATGR--FKDVLVLLMTDVLVFLQEKDQKYIFptlDKPSVVSLQNLIVRDIANQE----KGMFLISAAPP 519
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYKSKKDKKSY---KPKGSIDLSGCTVREAPDPDsskkPHCFEIKTSDR 77

                           90       100
                   ....*....|....*....|....*
gi 1174098421  520 EMYEVHTASRDDRSTWIRVIQQSVR 544
Cdd:smart00233  78 KTLLLQAESEEEREKWVEALRKAIA 102

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 1174098421 446 LIHDGCLLWKTATGRFKDVLVLLMTDVLVFLQEKDQKYIFPTLD-KPSVVSLQNLIVRDIANQEKGMFLISAAPPEMYEV 524
Cdd:cd15789     1 LKFEGTAWLKQARGKTKDVLVVVLTDVLFFLQEKDQKYVFVSPDnKAGVVSLQKLLVREKAGQEKRMFLISASPDGMPEM 80

                          90       100
                  ....*....|....*....|..
gi 1174098421 525 HTASRD---DRSTWIRVIQQSV 543
Cdd:cd15789    81 YELKVQkpkDKNTWIQTIRQAV 102

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 1174098421 446 LIHDGCLLWKTATGRFKDVLVLLMTDVLVFLQEKDQKYIFPTLD-KPSVVSLQNLIVRDIANQEKGMFLISA--APPEMY 522
Cdd:cd14680     1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDqKPPVICLQKLIVREVANEERGMFLISAssAGPEMY 80

                          90       100
                  ....*....|....*....|.
gi 1174098421 523 EVHTASRDDRSTWIRVIQQSV 543
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 1174098421  212 VIYELIQTELHHVRTLKIMTRLFRTGMLEEL-HLEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGstrnfviHR 290
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSV-------ER 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174098421  291 LGDLLISQfsgpsaEQMCKTYSEFCSRHSKALKLYKELyARDKRFQQFIRKVTRPAVLKRHGVQECILLVTQRITKYPLL 370
Cdd:smart00325  74 IGDVFLKL------EEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLL 146

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1174098421  371 ISRILQHSHGIEEERQDLTTALGLVKELLSNVDE 404
Cdd:smart00325 147 LKELLKHTPEDHEDREDLKKALKAIKELANQVNE 180

A-kinase anchoring protein 13 Pleckstrin homology (PH) domain; The Rho-specific GEF activity of AKAP13 (also called Brx-1, AKAP-Lbc, and proto-Lbc) mediates signaling downstream of G-protein coupled receptors and Toll-like receptor 2. It plays a role in cell growth, cell development and actin fiber formation. Protein kinase A (PKA) binds and phosphorylates AKAP13, regulating its Rho-GEF activity. 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, Brx) containing a dbl oncogene homology (DH) domain and PH domain which are required for full transforming activity. The DH domain is associated with guanine nucleotide exchange activation while the PH domain has multiple functions including determine protein sub-cellular localisation via phosphoinositide interactions, while others bind protein partners. Other ligands include protein kinase C which is bound by the PH domain of AKAP13, serving to activate protein kinase D and mobilize a cardiac hypertrophy signaling pathway. 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 1174098421 446 LIHDGCLLWKTATGRFKDVLVLLMTDVLVFLQEKDQKYIFPTLD-KPSVVSLQNLIVRDIANQEKGMFLISA--APPEMY 522
Cdd:cd13392     1 LVRDGPVSLKNTAGRLKEVQAVLLSDVLVFLQEKDQKYVFASLDqKSTVISLKKLIVREVAHEEKGLFLISMgiADPEMV 80

                          90       100
                  ....*....|....*....|...
gi 1174098421 523 EVHTASRDDRSTWIRVIQQSVRT 545
Cdd:cd13392    81 EVHASSKEERNSWMQIIQDTINT 103

Rho guanine nucleotide exchange factor Pleckstrin homology domain; 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 1174098421 446 LIHDGCLLWKTATGRFKDVLVLLMTDVLVFLQEKDQKYI--------FPTLD-KPSVVSLQNLIVRDIANQEKGMFLISA 516
Cdd:cd13329     1 LIHEGPLTWKVARGKLIEVHVLLLEDLLVLLQKQDDKYLlklhltgsFDSKDtKSPVIKLSTLLVREVATDKKAFFLIST 80

                          90       100
                  ....*....|....*....|....*....
gi 1174098421 517 AP--PEMYEVHTASRDDRSTWIRVIQQSV 543
Cdd:cd13329    81 SKngPQMYELVANSSSERKTWIKHISDAV 109

protein kinase C conserved region 1 (C1 domain) found in the 190 kDa guanine nucleotide exchange factor (p190RhoGEF)-like family; The p190RhoGEF-like protein family includes p190RhoGEF, Rho guanine nucleotide exchange factor 2 (ARHGEF2), A-kinase anchor protein 13 (AKAP-13) and similar proteins. p190RhoGEF 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. ARHGEF2 acts as a 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. AKAP-13 is a scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. It activates RhoA in response to signaling via G protein-coupled receptors via its function as 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. Members of this family share a common domain architecture containing C1, RhoGEF or Dbl-homologous (DH), and Pleckstrin Homology (PH) domains. Some members may contain additional domains such as the DUF5401 domain. 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1174098421  10 TNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIH-NRCKDTLANCTKV 62
Cdd:cd20815     1 KNTHQFVPVSFSNSTKCDVCSKPLTNKPALQCENCSVNVHdSSCKDQLADCTKF 54

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1174098421   6 DARYTNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCTKVKQ 64
Cdd:cd20876     1 KEKQSNGHQFVTGSFSGPTLCVVCDKPVTGKELLQCSNCTVNVHKGCKESAPPCTKKLQ 59

Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; LARG (also called RhoGEF12) 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. LARG contains a N-terminal extension, followed by Dbl homology (DH)-PH domains which bind and catalyze the exchange of GDP for GTP on RhoA in addition to a RGS domain. The active site of RhoA adopts two distinct GDP-excluding conformations among the four unique complexes in the asymmetric unit. The LARG PH domain also contains a potential protein-docking site. LARG forms a homotetramer via its DH domains. 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 1174098421 440 ELLRRKLIHDGCLLWKTATGRFKDVLVLLMTDVLVFLQEKDQKYIFPTLDK------------PSVVSLQNLIVRDIANQ 507
Cdd:cd13390    20 DLTKRKMIHEGPLTWKVNRDKTIDLYTLLLEDILVLLQKQDDRLVLRCHSKilastadskhtfSPVIKLNTVLVRQVATD 99

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1174098421 508 EKGMFLISAAP--PEMYEVHTASRDDRSTWIRVIQQ 541
Cdd:cd13390   100 NKAFFVISMSEngAQIYELVAQTVSEKTVWQDLITR 135

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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1174098421   13 HLFTTISVSGMTMCYACNKSI--TAKEALICPTCNVTIHNRCKDTL-ANC 59
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIwgSFKQGLRCSECKVKCHKKCADKVpKAC 50

protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor 18 (ARHGEF18)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate ARHGEF18, which is also called 114 kDa Rho-specific guanine nucleotide exchange factor (p114-Rho-GEF), p114RhoGEF, or septin-associated RhoGEF (SA-RhoGEF). ARHGEF18 acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. Its activation induces formation of actin stress fibers. ARHGEF18 also acts as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Members of this family contain C1, RhoGEF or Dbl-homologous (DH), and Pleckstrin Homology (PH) domains, as well as a DUF5401 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1174098421  10 TNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCT 60
Cdd:cd20879     1 VNGHQLVPGTFSSCATCSLCSKPLQNRNGLQCLNCAVNVHKNCKTLLTECS 51

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1174098421 446 LIHDGCLL--WKTATGRFKDVLVLLMTDVLVFLQEKDqkyIFPTLDKPSVVSLQNLIVRDIANQEKG----MFLI---SA 516
Cdd:pfam00169   1 VVKEGWLLkkGGGKKKSWKKRYFVLFDGSLLYYKDDK---SGKSKEPKGSISLSGCEVVEVVASDSPkrkfCFELrtgER 77

                          90       100
                  ....*....|....*....|....*...
gi 1174098421 517 APPEMYEVHTASRDDRSTWIRVIQQSVR 544
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSAIR 105

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1174098421  11 NGHLFTTISVSGMTMCYACNKSIT---AKEALICPTCNVTIHNRC 52
Cdd:cd20831     4 NDHTFVATHFKGGPSCAVCNKLIPgrfGKQGYQCRDCGLICHKRC 48

protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXb and similar proteins; Myosin-IXb, also called unconventional myosin-9b (Myo9b), is an actin-dependent motor protein of the unconventional myosin IX class. It is expressed abundantly in tissues of the immune system, like lymph nodes, thymus, and spleen, and in several immune cells including dendritic cells, macrophages and CD4+ T cells. Myosin-IXb contains a Ras-associating (RA) domain, a motor domain, a protein kinase C conserved region 1 (C1), and a Rho GTPase activating (RhoGAP) domain. Myosin-IXb acts as a motorized signaling molecule that links Rho signaling to the dynamic actin cytoskeleton. It regulates leukocyte migration by controlling RhoA signaling. Myosin-IXb is also involved in the development of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. Moreover, Myosin-IXb is a ROBO-interacting protein that suppresses RhoA activity in lung cancer cells. 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
                  ....*....|....*....|....*....|....*....|....
gi 1174098421  10 TNGHLFTTISVSGMTMCYACNKSITAKE-ALICPTCNVTIHNRC 52
Cdd:cd20884     3 YNGHVFTSYQVNIMQSCEQCSSYIWAMEkALLCSVCKMTCHKKC 46

protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; Myosins IX (Myo9) is a class of unique motor proteins with a common structure of an N-terminal extension preceding a myosin head homologous to the Ras-association (RA) domain, a head (motor) domain, a neck with IQ motifs that bind light chains, and a C-terminal tail containing cysteine-rich zinc binding (C1) and Rho-GTPase activating protein (RhoGAP) domains. There are two genes for myosins IX in humans, IXa and IXb, that are different in their expression and localization. IXa is expressed abundantly in brain and testis, and IXb is expressed abundantly in tissues of the immune system. 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
                  ....*....|....*....|....*....|....*....|...
gi 1174098421  11 NGHLFTTISVSGMTMCYACNKSITAKE-ALICPTCNVTIHNRC 52
Cdd:cd20818     2 NGHKFATVQFNIPTYCEVCNSFIWLMEkGLVCQVCKFTCHKKC 44

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1174098421 771 EKQATELALLQRQHALLQEELRRCRRLGEERATEAGSLEARLRESEQARALLEREAEEARRQLAAL 836
Cdd:COG1196   319 EELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEEL 384

protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene family encodes a family of neuron-specific, synaptic molecules that bind to syntaxin, an essential mediator of neurotransmitter release. Munc13-1 is a component of presynaptic active zones in which it acts as an essential synaptic vesicle priming protein. Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. 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 1174098421  13 HLFTTISVSGMTMCYACNKSI--TAKEALICPTCNVTIHNRCKDTL-ANC 59
Cdd:cd20807     1 HNFEVWTATTPTYCYECEGLLwgIARQGVRCTECGVKCHEKCKDLLnADC 50

protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. 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
                  ....*....|....*....|....*....|....*....|
gi 1174098421  24 TMCYACNKSI--TAKEALICPTCNVTIHNRCKDTLANCTK 61
Cdd:cd20817    12 TFCDVCKELLvgLSKQGLRCKNCKMNVHHKCQEGVPDCSG 51