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 1622829800  658 RRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPTLDKPSVVSLQNLIVRDIANQEKGMFLISAAPPEMY 737
Cdd:cd13393      1 RRKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLDKPAVISLQNLIVRDIANQEKGMFLISAAPPEMY 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1622829800  738 EVHTASRDDRSTWIRVIQQSVRICPSREDFPLIETE 773
Cdd:cd13393     81 EVHAASRDDRNTWMRLIQQTVKTCPSREEFPLIETE 116

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 1622829800  223 RYTNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCTKVKQKQQK 283
Cdd:cd20877      1 RYTNGHLFTTITVSGTTMCSACNKSITAKEALICPTCNVTIHNRCKDTLPNCTKVKQKQQK 61

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 1622829800  658 RRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPTLDKPSVVSLQNLIVRDIANQEKGMFLISAAPPEMY 737
Cdd:cd13393      1 RRKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLDKPAVISLQNLIVRDIANQEKGMFLISAAPPEMY 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1622829800  738 EVHTASRDDRSTWIRVIQQSVRICPSREDFPLIETE 773
Cdd:cd13393     81 EVHAASRDDRNTWMRLIQQTVKTCPSREEFPLIETE 116

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 1622829800   427 VIYELIQTELHHVRTLKIMTRLFRTGMLEELQ-LEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGstrnfviQR 505
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSV-------ER 73

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800   506 LGDLLISQfsgpsaEQMRKTYSEFCSRHTKALKLYKELyARDKRFQQFIRKVTRSAVLKRHGVQECILLVTQRITKYPVL 585
Cdd:smart00325   74 IGDVFLKL------EEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLL 146

                           170       180       190
                    ....*....|....*....|....*....|....
gi 1622829800   586 ISRILQHSHGIEEERQDLTTALGLVKELLSNVDQ 619
Cdd:smart00325  147 LKELLKHTPEDHEDREDLKKALKAIKELANQVNE 180

PH domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  651 FGREELLRRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPTLDKPS----------VVSLQNLIVRDIA 720
Cdd:pfam17838    7 FKKLDLTTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLACLSTGSenvdqktqspIISLKKLIVREVA 86

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1622829800  721 NQEKGMFLISAAP--PEMYEVHTASRDDRSTWIRVIQQSVR 759
Cdd:pfam17838   87 TDKKAFFLISTSPsdPQMYELHASTKSERNTWTKLIQDAIE 127

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 1622829800   228 HLFTTISVSGMTMCYACNKSI--TAKEALICPTCNVTIHNRCKDTL-ANC 274
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIwgSFKQGLRCSECKVKCHKKCADKVpKAC 50

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  923 QEEALQRLVNLYGLLHGLQAAVAQQDTLMEARFPEGPERREKLCRANSRDGEAGRAGAApvapekqaTELALLQRQHALL 1002
Cdd:COG4913    250 QIELLEPIRELAERYAAARERLAELEYLRAALRLWFAQRRLELLEAELEELRAELARLE--------AELERLEARLDAL 321

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622829800 1003 QEELRRCRRlgeERATEAG----SLEARLRESEQARALLEREAEEARRQLAALGQTEPLPAEAPWARR 1066
Cdd:COG4913    322 REELDELEA---QIRGNGGdrleQLEREIERLERELEERERRRARLEALLAALGLPLPASAEEFAALR 386

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  987 KQATELALLQRQHALLQEELRRC---RRLGEERATE---AGSLEARLRESEQARALLEREAEEARRQLaalgQTEPLPAE 1060
Cdd:pfam15558   18 KEEQRMRELQQQAALAWEELRRRdqkRQETLERERRlllQQSQEQWQAEKEQRKARLGREERRRADRR----EKQVIEKE 93

                           90
                   ....*....|...
gi 1622829800 1061 APWARRPVDPRRR 1073
Cdd:pfam15558   94 SRWREQAEDQENQ 106

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 1622829800  658 RRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPTLDKPSVVSLQNLIVRDIANQEKGMFLISAAPPEMY 737
Cdd:cd13393      1 RRKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLDKPAVISLQNLIVRDIANQEKGMFLISAAPPEMY 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1622829800  738 EVHTASRDDRSTWIRVIQQSVRICPSREDFPLIETE 773
Cdd:cd13393     81 EVHAASRDDRNTWMRLIQQTVKTCPSREEFPLIETE 116

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 1622829800  661 LIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPTLD-KPSVVSLQNLIVRDIANQEKGMFLISAAPPEMYEV 739
Cdd:cd15789      1 LKFEGTAWLKQARGKTKDVLVVVLTDVLFFLQEKDQKYVFVSPDnKAGVVSLQKLLVREKAGQEKRMFLISASPDGMPEM 80

                           90       100
                   ....*....|....*....|..
gi 1622829800  740 HTASRD---DRSTWIRVIQQSV 758
Cdd:cd15789     81 YELKVQkpkDKNTWIQTIRQAV 102

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 1622829800  424 QQDVIYELIQTELHHVRTLKIMTRLFRTGMLEELQ-LEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGstrnfv 502
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG------ 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  503 iQRLGDLLISQFSgpsaeqMRKTYSEFCSRHTKALKLYKELYARDKRFQQFIRKVTRSAvlKRHGVQECILLVTQRITKY 582
Cdd:cd00160     75 -PRIGDVFLKLAP------FFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESEC--GRLKLESLLLKPVQRLTKY 145

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1622829800  583 PVLISRILQHSHGIEEERQDLTTALGLVKELLSNVD 618
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 1622829800  223 RYTNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCTKVKQKQQK 283
Cdd:cd20877      1 RYTNGHLFTTITVSGTTMCSACNKSITAKEALICPTCNVTIHNRCKDTLPNCTKVKQKQQK 61

PH domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  651 FGREELLRRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPTLDKPS----------VVSLQNLIVRDIA 720
Cdd:pfam17838    7 FKKLDLTTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLACLSTGSenvdqktqspIISLKKLIVREVA 86

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1622829800  721 NQEKGMFLISAAP--PEMYEVHTASRDDRSTWIRVIQQSVR 759
Cdd:pfam17838   87 TDKKAFFLISTSPsdPQMYELHASTKSERNTWTKLIQDAIE 127

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 1622829800  427 VIYELIQTELHHVRTLKIMTRLFRTGMLEELQLEPGVVQGLFPCVDELSDIHTRFLsqlLERRRQAlcpgstrNFVIQRL 506
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---LEELLKE-------WISIQRI 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  507 GDLLISQFSGPsaeqmrKTYSEFCSRHTKALKLYKELYARDKRFQQFIRKVTRSAVLKRHGVQECILLVTQRITKYPVLI 586
Cdd:pfam00621   71 GDIFLKFAPGF------KVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1622829800  587 SRILQHSHGIEEERQDLTTALGLVKELLSNVD 618
Cdd:pfam00621  145 KELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  221 DARYTNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCTKVKQK 280
Cdd:cd20878      1 DKKTLNGHVFSPVSSVGPTQCYHCSKPLNTKDAFLCANCNVQVHKGCRESLPVCAKVKMK 60

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 1622829800  636 RMD--PRAQTPVPGKGPFGREELLRRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPTLDKPS------ 707
Cdd:cd13391      1 RLDatALERASNPLAAEFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLKCHSKTAvgssds 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  708 ------VVSLQNLIVRDIANQEKGMFLI--SAAPPEMYEVHTASRDDRSTWIRVIQQSVR 759
Cdd:cd13391     81 kqtfspVLKLNSVLIRSVATDKRALFIIctSKLGPQIYELVALTSSEKNTWMELLEEAVR 140

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 1622829800   228 HLFTTISVSGMTMCYACNKSI--TAKEALICPTCNVTIHNRCKDTL-ANC 274
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIwgSFKQGLRCSECKVKCHKKCADKVpKAC 50

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 1622829800   661 LIHDGCLLWKTATGR--FKDVLMLLMTDVLVFLQEKDQKYIFptlDKPSVVSLQNLIVRDIANQE----KGMFLISAAPP 734
Cdd:smart00233    1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYKSKKDKKSY---KPKGSIDLSGCTVREAPDPDsskkPHCFEIKTSDR 77

                            90       100
                    ....*....|....*....|....*
gi 1622829800   735 EMYEVHTASRDDRSTWIRVIQQSVR 759
Cdd:smart00233   78 KTLLLQAESEEEREKWVEALRKAIA 102

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 1622829800  225 TNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCT 275
Cdd:cd20879      1 VNGHQLVPGTFSSCATCSLCSKPLQNRNGLQCLNCAVNVHKNCKTLLTECS 51

protein kinase C conserved region 1 (C1 domain) superfamily; 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 the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1622829800  228 HLFTTISVSGMTMCYACNKSIT--AKEALICPTCNVTIHNRCKDTLA-NC 274
Cdd:cd00029      1 HRFVPTTFSSPTFCDVCGKLIWglFKQGLKCSDCGLVCHKKCLDKAPsPC 50

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622829800  924 EEALQRLVNLYGLLHGLQAAV----AQQDTLMEARfpegpERREKLcRANSRDGEAGRAGAAPVAPEKQATELALLQRQH 999
Cdd:COG4913    224 FEAADALVEHFDDLERAHEALedarEQIELLEPIR-----ELAERY-AAARERLAELEYLRAALRLWFAQRRLELLEAEL 297

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622829800 1000 ALLQEELRRcrrlgeerateagsLEARLRESEQARALLEREAEEARRQLAALG--QTEPLPAEAPWARRPVDPRRRSL 1075
Cdd:COG4913    298 EELRAELAR--------------LEAELERLEARLDALREELDELEAQIRGNGgdRLEQLEREIERLERELEERERRR 361

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 1622829800  225 TNGHLFTTISVSGMTMCYACNKSITAKE-ALICPTCNVTIHNRC 267
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 1622829800  226 NGHLFTTISVSGMTMCYACNKSITAKE-ALICPTCNVTIHNRC 267
Cdd:cd20818      2 NGHKFATVQFNIPTYCEVCNSFIWLMEkGLVCQVCKFTCHKKC 44

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622829800  986 EKQATELALLQRQHALLQEELRRCRRLGEERATEAGSLEARLRESEQARALLEREAEEARRQLAAL 1051
Cdd:COG1196    319 EELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEEL 384

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 5 (RASSF5) and similar proteins; RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. It is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. It contains a C1 domain, which is descibed in this model. 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 1622829800  227 GHLFTTISVSGmTMCYACNKSITAkEALICPTCNVTIHNRCKD 269
Cdd:cd20886      3 GHRFEPGALGP-GWCDLCGRYILS-QALRCTNCKYTCHSECRD 43

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 1622829800  239 TMCYACNKSI--TAKEALICPTCNVTIHNRCKDTLANCTK 276
Cdd:cd20817     12 TFCDVCKELLvgLSKQGLRCKNCKMNVHHKCQEGVPDCSG 51