Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  707 LLHDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQKLIAREVANEERGMFLISASSAGPEMY 786
Cdd:cd14680     1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPPVICLQKLIVREVANEERGMFLISASSAGPEMY 80

                          90       100
                  ....*....|....*....|.
gi 568984205  787 EIHTNSKEERNNWMRRIQQAV 807
Cdd:cd14680    81 EIHTSSKEERNNWMRLIQEAV 101

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  269 KEKMNRHQFVPGTFSGVLQCSGCDKTLLGKESLQCANCKANTHKGCKDAVPPCTKKFQEK 328
Cdd:cd20876     2 EKQSNGHQFVTGSFSGPTLCVVCDKPVTGKELLQCSNCTVNVHKGCKESAPPCTKKLQDK 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 568984205  707 LLHDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQKLIAREVANEERGMFLISASSAGPEMY 786
Cdd:cd14680     1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPPVICLQKLIVREVANEERGMFLISASSAGPEMY 80

                          90       100
                  ....*....|....*....|.
gi 568984205  787 EIHTNSKEERNNWMRRIQQAV 807
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 568984205    473 VIFELMQTEVHHIQTLLIMSEVFRKGMKEELQ-LDHSTVDKIFPCLDELLETHRHFFFSMKERRQESCAGSDRnfvinqI 551
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSVER------I 74

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205    552 GDILVQQfseenaSKMKRIYGEFCSHHKEAMSLFKELQQNKKFQNFIKIRNSNLLARRRGIPECILLVTQRITKYPVLVE 631
Cdd:smart00325   75 GDVFLKL------EEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|.
gi 568984205    632 RILQYTKERTEEHRDLCKALGLIKDMIAAVD 662
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVN 179

PH domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205   689 LKNGHVFRKQALlsQERALLHDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAA-------VDQK--PSVISLQ 759
Cdd:pfam17838    1 HPLGEEFKKLDL--TTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLAClstgsenVDQKtqSPIISLK 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 568984205   760 KLIAREVANEERGMFLISASSAGPEMYEIHTNSKEERNNWMRRIQQAVE 808
Cdd:pfam17838   79 KLIVREVATDKKAFFLISTSPSDPQMYELHASTKSERNTWTKLIQDAIE 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 568984205    275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVP-PC 321
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGsfKQGLRCSECKVKCHKKCADKVPkAC 50

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  437 IDLSSDAQEFEAESWSLVVDPSFCSRQEKDVIKRQDVIFELMQTEVHHIQTLLIMSEVFRKGMkEELQLDHSTVDK---- 512
Cdd:COG5422   452 SSLALDKFDEEKNLWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPL-EESNIIPENARRnfik 530

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  513 -IFPCLDELLETHRHFFFSMKERRQESCagsdrnfVINQIGDILVQQ--FSEENASKMK-RIYGEFCSHhkeamslfKEL 588
Cdd:COG5422   531 hVFANINEIYAVNSKLLKALTNRQCLSP-------IVNGIADIFLDYvpKFEPFIKYGAsQPYAKYEFE--------REK 595

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  589 QQNKKFQNF---IKIRNSnllARRRGIPECILLVTQRITKYPVLVERILQYTKERTEEHRDLCKALGLIKDMIAAVDLkv 665
Cdd:COG5422   596 SVNPNFARFdheVERLDE---SRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNF-- 670

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 568984205  666 sEYEKNQKWLEILnkiENKTYTKLKNGHVfrKQALLSQERALLHDGLV 713
Cdd:COG5422   671 -ESGKAENRGDLF---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 568984205  707 LLHDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQKLIAREVANEERGMFLISASSAGPEMY 786
Cdd:cd14680     1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPPVICLQKLIVREVANEERGMFLISASSAGPEMY 80

                          90       100
                  ....*....|....*....|.
gi 568984205  787 EIHTNSKEERNNWMRRIQQAV 807
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 568984205  470 RQDVIFELMQTEVHHIQTLLIMSEVFRKGMKEELQ-LDHSTVDKIFPCLDELLETHRHFFFSMKERRQESCAGSDRnfvi 548
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPR---- 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  549 nqIGDILVQQFSeenaskMKRIYGEFCSHHKEAMSLFKELQQ-NKKFQNFIKIRNSNllARRRGIPECILLVTQRITKYP 627
Cdd:cd00160    77 --IGDVFLKLAP------FFKIYSEYCSNHPDALELLKKLKKfNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYP 146

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 568984205  628 VLVERILQYTKERTEEHRDLCKALGLIKDMIAAVD 662
Cdd:cd00160   147 LLLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

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 568984205  705 RALLHDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDqKPSVISLQKLIAREVANEERGMFLISAssAGPE 784
Cdd:cd13393     2 RKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLD-KPAVISLQNLIVRDIANQEKGMFLISA--APPE 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 568984205  785 MYEIHTNSKEERNNWMRRIQQAVESCPEEE 814
Cdd:cd13393    79 MYEVHAASRDDRNTWMRLIQQTVKTCPSRE 108

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 568984205   473 VIFELMQTEVHHIQTLLIMSEVFRKGMKEELQLDHSTVDKIFPCLDELLETHRHFFfsMKERRQEscagsdrNFVINQIG 552
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKE-------WISIQRIG 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205   553 DILVQQFSeenaskMKRIYGEFCSHHKEAMSLFKELQQ-NKKFQNFIKIRNSNLLARRRGIPECILLVTQRITKYPVLVE 631
Cdd:pfam00621   72 DIFLKFAP------GFKVYSTYCSNYPKALKLLKKLLKkNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 568984205   632 RILQYTKERTEEHRDLCKALGLIKDMIAAVD 662
Cdd:pfam00621  146 ELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176

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 568984205  707 LLHDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYI--------FAAVDQKPSVISLQKLIAREVANEERGMFLISA 778
Cdd:cd13329     1 LIHEGPLTWKVARGKLIEVHVLLLEDLLVLLQKQDDKYLlklhltgsFDSKDTKSPVIKLSTLLVREVATDKKAFFLIST 80

                          90       100
                  ....*....|....*....|....*....
gi 568984205  779 SSAGPEMYEIHTNSKEERNNWMRRIQQAV 807
Cdd:cd13329    81 SKNGPQMYELVANSSSERKTWIKHISDAV 109

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 568984205  269 KEKMNRHQFVPGTFSGVLQCSGCDKTLLGKESLQCANCKANTHKGCKDAVPPCTKKFQEK 328
Cdd:cd20876     2 EKQSNGHQFVTGSFSGPTLCVVCDKPVTGKELLQCSNCTVNVHKGCKESAPPCTKKLQDK 61

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 568984205  268 EKEKMNRHQFVPGTFSGVLQCSGCDKTLLGKESLQCANCKANTHKGCKDAVPPCTK 323
Cdd:cd20878     1 DKKTLNGHVFSPVSSVGPTQCYHCSKPLNTKDAFLCANCNVQVHKGCRESLPVCAK 56

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 568984205  705 RALLHDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIF--------AAVDQKPS---VISLQKLIAREVANEERGM 773
Cdd:cd13391    26 RRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLkchsktavGSSDSKQTfspVLKLNSVLIRSVATDKRAL 105

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568984205  774 FLISASSAGPEMYEIHTNSKEERNNWMRRIQQAV 807
Cdd:cd13391   106 FIICTSKLGPQIYELVALTSSEKNTWMELLEEAV 139

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 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVP-PC 321
Cdd:cd00029     1 HRFVPTTFSSPTFCDVCGKLIWGlfKQGLKCSDCGLVCHKKCLDKAPsPC 50

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 568984205   275 HQFVPGTFSGVLQCSGCDKTLLGKES--LQCANCKANTHKGCKDAVPPC 321
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKqgLKCSWCKLNVHKRCHEKVPPE 49

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  437 IDLSSDAQEFEAESWSLVVDPSFCSRQEKDVIKRQDVIFELMQTEVHHIQTLLIMSEVFRKGMkEELQLDHSTVDK---- 512
Cdd:COG5422   452 SSLALDKFDEEKNLWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPL-EESNIIPENARRnfik 530

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  513 -IFPCLDELLETHRHFFFSMKERRQESCagsdrnfVINQIGDILVQQ--FSEENASKMK-RIYGEFCSHhkeamslfKEL 588
Cdd:COG5422   531 hVFANINEIYAVNSKLLKALTNRQCLSP-------IVNGIADIFLDYvpKFEPFIKYGAsQPYAKYEFE--------REK 595

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568984205  589 QQNKKFQNF---IKIRNSnllARRRGIPECILLVTQRITKYPVLVERILQYTKERTEEHRDLCKALGLIKDMIAAVDLkv 665
Cdd:COG5422   596 SVNPNFARFdheVERLDE---SRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNF-- 670

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 568984205  666 sEYEKNQKWLEILnkiENKTYTKLKNGHVfrKQALLSQERALLHDGLV 713
Cdd:COG5422   671 -ESGKAENRGDLF---HLNQQLLFKPEYV--NLGLNDEYRKIIFKGVL 712

protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor (ARHGEF)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate Rho guanine nucleotide exchange factors ARHGEF11 and ARHGEF12, which may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Unlike typical ARHGEF11 and ARHGEF12, members of this family contain a C1 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
                  ....*....|....*....|....*....|....*....|....*.
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTL--LGKESLQCANCKANTHKGCKDAV 318
Cdd:cd20832     2 HQFVLQHYYQVTFCNHCSGLLwgIGYQGYQCSDCEFNIHKQCIEVI 47

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVPP 320
Cdd:cd20809     1 HKFIVRTFSTPTKCNHCTSLMVGlvRQGLVCEVCGYACHVSCADKAPQ 48

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGC-KDAVPPC 321
Cdd:cd20830     1 HRFVEQSFSTLQWCDKCGKFLFGlvHQGLQCQDCGLVCHRTCaATGLPKC 50

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568984205  275 HQFVPGT--FSGVlqCSGCDKTL-LGKESLQCANCKANTHKGCKDAVP-PC 321
Cdd:cd20821     3 HRFVSKTviKPET--CVVCGKRIkFGKKALKCKDCRVVCHPDCKDKLPlPC 51

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVPPC 321
Cdd:cd20810     3 HSFELTTFKEPTTCSVCKKLLKGlfFQGYKCSVCGAAVHKECIAKVKRC 51

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568984205  275 HQFVPGTFSGVLQCSGCDKT---LLGKESLQCANCKANTHKGCKDAVP 319
Cdd:cd20893     6 HQWLEGNLPVSAKCTVCDKTcgsVLRLQDWRCLWCKAMVHTSCKELLL 53

second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVPP 320
Cdd:cd20836     1 HKFKVHTYSSPTFCDHCGSLLYGliHQGMKCDTCDMNVHKRCVKNVPS 48

first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), 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 domains. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTL--LGKESLQCANCKANTHKGC-KDAVPPCTK 323
Cdd:cd20792     2 HKFVATFFKQPTFCSHCKDFIwgLGKQGYQCQVCRFVVHKRChEYVVFKCPG 53

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568984205  273 NRHQFVPGTFSGVLQCSGCDKTLLGK--ESLQCANCKANTHKGCKDAVPPC 321
Cdd:cd20868     4 NHHNFQMYTFDKTTNCKACKMLLRGTfyQGYYCSKCGAGAHKECLEVIPPC 54

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second 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 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVP 319
Cdd:cd20844     6 HTFAVHSYTRPTICQYCKRLLKGlfRQGMQCKDCRFNCHKRCASKVP 52

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, 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-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVP 319
Cdd:cd20837     1 HRFKVYNYMSPTFCDHCGSLLWGlfRQGLKCEECGMNVHHKCQKKVA 47

protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and plays a role in regulating androgen receptor transcriptional activity. 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568984205  273 NRHQFVPGTFSGVLQCSGCDKTLLGK--ESLQCANCKANTHKGCKDAVPPCTK 323
Cdd:cd20869     7 NSHDFKMHTFERVTSCKVCQMLLRGTfyQGYLCSKCGAGAHKECLGRLDSCGR 59

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDA 317
Cdd:cd20797     4 HVVEVEQYMTPTFCDYCGEMLTGlmKQGVKCKNCRCNFHKRCANA 48

second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), 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. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVPPC 321
Cdd:cd20793     1 HKFKVHTYYSPTFCDHCGSLLYGlvRQGLKCKDCGMNVHHRCKENVPHL 49

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase gamma (MRCK gamma) and similar proteins; MRCK gamma (MRCKG), also called Cdc42-binding protein kinase gamma, DMPK-like gamma, myotonic dystrophy protein kinase-like gamma, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed in heart and skeletal muscles. It may act as a downstream effector of Cdc42 in cytoskeletal reorganization and contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation. 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 568984205  275 HQFVPGTFSGVLQCSGCDKTLLG--KESLQCANCKANTHKGCKDAVPPC 321
Cdd:cd20866     1 HTFKPKTFTSPTKCLRCTSLMVGlvRQGLACEACNYVCHVSCAEGAPIC 49