LGR5_HUMAN
ID LGR5_HUMAN Reviewed; 907 AA.
AC O75473; D8MCT0; Q4VAM0; Q4VAM2; Q9UP75;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 5;
DE AltName: Full=G-protein coupled receptor 49;
DE AltName: Full=G-protein coupled receptor 67;
DE AltName: Full=G-protein coupled receptor HG38;
DE Flags: Precursor;
GN Name=LGR5; Synonyms=GPR49, GPR67;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9642114; DOI=10.1006/bbrc.1998.8774;
RA McDonald T., Wang R., Bailey W., Xie G., Chen F., Caskey C.T., Liu Q.;
RT "Identification and cloning of an orphan G protein-coupled receptor of the
RT glycoprotein hormone receptor subfamily.";
RL Biochem. Biophys. Res. Commun. 247:266-270(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=9849958; DOI=10.1210/mend.12.12.0211;
RA Hsu S.Y., Liang S.-G., Hsueh A.J.W.;
RT "Characterization of two LGR genes homologous to gonadotropin and
RT thyrotropin receptors with extracellular leucine-rich repeats and a G
RT protein-coupled, seven-transmembrane region.";
RL Mol. Endocrinol. 12:1830-1845(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Rot S., Taubert H., Bache M., Vordermark D., Kappler M.;
RT "Alternatively spliced transcript of the GPR49-mRNA occur in different
RT tumor cell lines and soft tissue sarcoma.";
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ALA-666.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=12601349; DOI=10.1053/jhep.2003.50029;
RA Yamamoto Y., Sakamoto M., Fujii G., Tsuiji H., Kenetaka K., Asaka M.,
RA Hirohashi S.;
RT "Overexpression of orphan G-protein-coupled receptor, Gpr49, in human
RT hepatocellular carcinomas with beta-catenin mutations.";
RL Hepatology 37:528-533(2003).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=16575208; DOI=10.4161/cbt.5.4.2521;
RA McClanahan T., Koseoglu S., Smith K., Grein J., Gustafson E., Black S.,
RA Kirschmeier P., Samatar A.A.;
RT "Identification of overexpression of orphan G protein-coupled receptor
RT GPR49 in human colon and ovarian primary tumors.";
RL Cancer Biol. Ther. 5:419-426(2006).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=19030762; DOI=10.1100/tsw.2008.148;
RA Becker L., Huang Q., Mashimo H.;
RT "Immunostaining of Lgr5, an intestinal stem cell marker, in normal and
RT premalignant human gastrointestinal tissue.";
RL ScientificWorldJournal 8:1168-1176(2008).
RN [9]
RP FUNCTION, AND INTERACTION WITH RSPO1; RSPO2; RSPO3 AND RSPO4.
RX PubMed=21909076; DOI=10.1038/embor.2011.175;
RA Glinka A., Dolde C., Kirsch N., Huang Y.L., Kazanskaya O., Ingelfinger D.,
RA Boutros M., Cruciat C.M., Niehrs C.;
RT "LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and
RT Wnt/PCP signalling.";
RL EMBO Rep. 12:1055-1061(2011).
RN [10]
RP FUNCTION, AND INTERACTION WITH RSPO1; RSPO2; RSPO3 AND RSPO4.
RX PubMed=21727895; DOI=10.1038/nature10337;
RA de Lau W., Barker N., Low T.Y., Koo B.K., Li V.S., Teunissen H., Kujala P.,
RA Haegebarth A., Peters P.J., van de Wetering M., Stange D.E., van Es J.E.,
RA Guardavaccaro D., Schasfoort R.B., Mohri Y., Nishimori K., Mohammed S.,
RA Heck A.J., Clevers H.;
RT "Lgr5 homologues associate with Wnt receptors and mediate R-spondin
RT signalling.";
RL Nature 476:293-297(2011).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RSPO1; RSPO2; RSPO3
RP AND RSPO4.
RX PubMed=21693646; DOI=10.1073/pnas.1106083108;
RA Carmon K.S., Gong X., Lin Q., Thomas A., Liu Q.;
RT "R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to
RT regulate Wnt/beta-catenin signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11452-11457(2011).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RSPO1.
RX PubMed=22815884; DOI=10.1371/journal.pone.0040976;
RA Ruffner H., Sprunger J., Charlat O., Leighton-Davies J., Grosshans B.,
RA Salathe A., Zietzling S., Beck V., Therier M., Isken A., Xie Y., Zhang Y.,
RA Hao H., Shi X., Liu D., Song Q., Clay I., Hintzen G., Tchorz J.,
RA Bouchez L.C., Michaud G., Finan P., Myer V.E., Bouwmeester T., Porter J.,
RA Hild M., Bassilana F., Parker C.N., Cong F.;
RT "R-Spondin potentiates Wnt/beta-catenin signaling through orphan receptors
RT LGR4 and LGR5.";
RL PLoS ONE 7:E40976-E40976(2012).
RN [13]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-861 AND SER-864.
RX PubMed=23439653; DOI=10.1074/jbc.m112.447540;
RA Snyder J.C., Rochelle L.K., Lyerly H.K., Caron M.G., Barak L.S.;
RT "Constitutive Internalization of the Leucine-rich G Protein-coupled
RT Receptor-5 (LGR5) to the Trans-Golgi Network.";
RL J. Biol. Chem. 288:10286-10297(2013).
RN [14]
RP INTERACTION WITH RSPO2.
RX PubMed=29769720; DOI=10.1038/s41586-018-0118-y;
RA Szenker-Ravi E., Altunoglu U., Leushacke M., Bosso-Lefevre C., Khatoo M.,
RA Thi Tran H., Naert T., Noelanders R., Hajamohideen A., Beneteau C.,
RA de Sousa S.B., Karaman B., Latypova X., Basaran S., Yuecel E.B., Tan T.T.,
RA Vlaminck L., Nayak S.S., Shukla A., Girisha K.M., Le Caignec C.,
RA Soshnikova N., Uyguner Z.O., Vleminckx K., Barker N., Kayserili H.,
RA Reversade B.;
RT "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently
RT of LGR4/5/6.";
RL Nature 557:564-569(2018).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 22-543 IN COMPLEX WITH RSPO1,
RP FUNCTION, MUTAGENESIS OF ASP-146; ASP-170 AND ALA-190, AND DISULFIDE BONDS.
RX PubMed=23809763; DOI=10.1016/j.celrep.2013.06.009;
RA Peng W.C., de Lau W., Forneris F., Granneman J.C., Huch M., Clevers H.,
RA Gros P.;
RT "Structure of stem cell growth factor R-spondin 1 in complex with the
RT ectodomain of its receptor LGR5.";
RL Cell Rep. 3:1885-1892(2013).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 32-557 IN COMPLEX WITH RNF43 AND
RP RSPO1, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-208.
RX PubMed=23756651; DOI=10.1101/gad.219915.113;
RA Chen P.H., Chen X., Lin Z., Fang D., He X.;
RT "The structural basis of R-spondin recognition by LGR5 and RNF43.";
RL Genes Dev. 27:1345-1350(2013).
CC -!- FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt
CC signaling pathway and acts as a stem cell marker of the intestinal
CC epithelium and the hair follicle. Upon binding to R-spondins (RSPO1,
CC RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and
CC frizzled receptors that are activated by extracellular Wnt receptors,
CC triggering the canonical Wnt signaling pathway to increase expression
CC of target genes. In contrast to classical G-protein coupled receptors,
CC does not activate heterotrimeric G-proteins to transduce the signal.
CC Involved in the development and/or maintenance of the adult intestinal
CC stem cells during postembryonic development.
CC {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895,
CC ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22815884,
CC ECO:0000269|PubMed:23809763}.
CC -!- SUBUNIT: Identified in a complex composed of RNF43, LGR5 and RSPO1
CC (PubMed:21909076, PubMed:21727895, PubMed:21693646, PubMed:22815884,
CC PubMed:23809763, PubMed:23756651). Also interacts with other R-spondin
CC ligands, including RSPO2, RSPO3 and RSPO4 (PubMed:21909076,
CC PubMed:21727895, PubMed:21693646, PubMed:29769720).
CC {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895,
CC ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22815884,
CC ECO:0000269|PubMed:23756651, ECO:0000269|PubMed:23809763,
CC ECO:0000269|PubMed:29769720}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Golgi
CC apparatus, trans-Golgi network membrane; Multi-pass membrane protein.
CC Note=Rapidly and constitutively internalized to the trans-Golgi network
CC at steady state. Internalization to the trans-Golgi network may be the
CC result of phosphorylation at Ser-861 and Ser-864; however, the
CC phosphorylation event has not been proven (PubMed:23439653).
CC {ECO:0000269|PubMed:23439653}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O75473-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75473-2; Sequence=VSP_037746;
CC Name=3;
CC IsoId=O75473-3; Sequence=VSP_054782;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, placenta, spinal
CC cord, and various region of brain. Expressed at the base of crypts in
CC colonic and small mucosa stem cells. In premalignant cancer expression
CC is not restricted to the cript base. Overexpressed in cancers of the
CC ovary, colon and liver. {ECO:0000269|PubMed:12601349,
CC ECO:0000269|PubMed:16575208, ECO:0000269|PubMed:19030762}.
CC -!- MISCELLANEOUS: LGR5 is used as a marker of adult tissue stem cells in
CC the intestine, stomach, hair follicle, and mammary epithelium.
CC {ECO:0000305|PubMed:19030762}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF062006; AAC28019.1; -; mRNA.
DR EMBL; AF061444; AAC77911.1; -; mRNA.
DR EMBL; FN820440; CBL95002.2; -; mRNA.
DR EMBL; AC078860; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090116; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096324; AAH96324.1; -; mRNA.
DR EMBL; BC096325; AAH96325.1; -; mRNA.
DR EMBL; BC096326; AAH96326.1; -; mRNA.
DR EMBL; BC099650; AAH99650.1; -; mRNA.
DR CCDS; CCDS61194.1; -. [O75473-2]
DR CCDS; CCDS61195.1; -. [O75473-3]
DR CCDS; CCDS9000.1; -. [O75473-1]
DR PIR; JE0176; JE0176.
DR RefSeq; NP_001264155.1; NM_001277226.1. [O75473-2]
DR RefSeq; NP_001264156.1; NM_001277227.1. [O75473-3]
DR RefSeq; NP_003658.1; NM_003667.3. [O75473-1]
DR PDB; 4BSR; X-ray; 3.20 A; A/B=22-543.
DR PDB; 4BSS; X-ray; 3.20 A; A/B/E/F=22-543.
DR PDB; 4BST; X-ray; 4.30 A; A/B=22-543.
DR PDB; 4BSU; X-ray; 3.20 A; A/B/E/F=22-543.
DR PDB; 4KNG; X-ray; 2.50 A; A/B=32-557.
DR PDB; 4UFR; X-ray; 2.20 A; A/C=32-486, A/C=538-544.
DR PDB; 4UFS; X-ray; 4.80 A; A=32-486, A=538-544.
DR PDBsum; 4BSR; -.
DR PDBsum; 4BSS; -.
DR PDBsum; 4BST; -.
DR PDBsum; 4BSU; -.
DR PDBsum; 4KNG; -.
DR PDBsum; 4UFR; -.
DR PDBsum; 4UFS; -.
DR AlphaFoldDB; O75473; -.
DR SMR; O75473; -.
DR BioGRID; 114119; 13.
DR CORUM; O75473; -.
DR IntAct; O75473; 2.
DR STRING; 9606.ENSP00000266674; -.
DR GuidetoPHARMACOLOGY; 148; -.
DR GlyGen; O75473; 6 sites.
DR iPTMnet; O75473; -.
DR PhosphoSitePlus; O75473; -.
DR BioMuta; LGR5; -.
DR jPOST; O75473; -.
DR MassIVE; O75473; -.
DR MaxQB; O75473; -.
DR PaxDb; O75473; -.
DR PeptideAtlas; O75473; -.
DR PRIDE; O75473; -.
DR ProteomicsDB; 15173; -.
DR ProteomicsDB; 50034; -. [O75473-1]
DR ProteomicsDB; 50035; -. [O75473-2]
DR ABCD; O75473; 15 sequenced antibodies.
DR Antibodypedia; 1987; 895 antibodies from 42 providers.
DR DNASU; 8549; -.
DR Ensembl; ENST00000266674.10; ENSP00000266674.4; ENSG00000139292.13. [O75473-1]
DR Ensembl; ENST00000536515.5; ENSP00000443033.1; ENSG00000139292.13. [O75473-3]
DR Ensembl; ENST00000540815.2; ENSP00000441035.2; ENSG00000139292.13. [O75473-2]
DR GeneID; 8549; -.
DR KEGG; hsa:8549; -.
DR MANE-Select; ENST00000266674.10; ENSP00000266674.4; NM_003667.4; NP_003658.1.
DR UCSC; uc001swl.5; human. [O75473-1]
DR CTD; 8549; -.
DR DisGeNET; 8549; -.
DR GeneCards; LGR5; -.
DR HGNC; HGNC:4504; LGR5.
DR HPA; ENSG00000139292; Tissue enhanced (brain, fallopian tube, placenta, skeletal muscle).
DR MIM; 606667; gene.
DR neXtProt; NX_O75473; -.
DR OpenTargets; ENSG00000139292; -.
DR PharmGKB; PA28894; -.
DR VEuPathDB; HostDB:ENSG00000139292; -.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000160214; -.
DR HOGENOM; CLU_006843_0_0_1; -.
DR InParanoid; O75473; -.
DR OMA; LHHNEIY; -.
DR PhylomeDB; O75473; -.
DR TreeFam; TF316814; -.
DR PathwayCommons; O75473; -.
DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination.
DR SignaLink; O75473; -.
DR SIGNOR; O75473; -.
DR BioGRID-ORCS; 8549; 14 hits in 1066 CRISPR screens.
DR ChiTaRS; LGR5; human.
DR GeneWiki; LGR5; -.
DR GenomeRNAi; 8549; -.
DR Pharos; O75473; Tbio.
DR PRO; PR:O75473; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O75473; protein.
DR Bgee; ENSG00000139292; Expressed in hair follicle and 152 other tissues.
DR ExpressionAtlas; O75473; baseline and differential.
DR Genevisible; O75473; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR GO; GO:0016500; F:protein-hormone receptor activity; IEA:InterPro.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:UniProtKB.
DR GO; GO:2001013; P:epithelial cell proliferation involved in renal tubule morphogenesis; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0009994; P:oocyte differentiation; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002131; Gphrmn_rcpt_fam.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF00560; LRR_1; 1.
DR Pfam; PF13855; LRR_8; 4.
DR Pfam; PF01462; LRRNT; 1.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM00369; LRR_TYP; 15.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR PROSITE; PS51450; LRR; 15.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Golgi apparatus;
KW Leucine-rich repeat; Membrane; Receptor; Reference proteome; Repeat;
KW Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..907
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 5"
FT /id="PRO_0000012794"
FT TOPO_DOM 22..561
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 562..582
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 583..593
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 594..614
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 615..638
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 639..659
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 660..682
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 683..703
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 704..722
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 723..743
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 744..767
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 768..788
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 789..802
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 803..823
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 824..907
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..66
FT /note="LRRNT"
FT REPEAT 67..90
FT /note="LRR 1"
FT REPEAT 91..112
FT /note="LRR 2"
FT REPEAT 115..136
FT /note="LRR 3"
FT REPEAT 139..160
FT /note="LRR 4"
FT REPEAT 163..184
FT /note="LRR 5"
FT REPEAT 187..208
FT /note="LRR 6"
FT REPEAT 211..232
FT /note="LRR 7"
FT REPEAT 235..256
FT /note="LRR 8"
FT REPEAT 258..279
FT /note="LRR 9"
FT REPEAT 282..303
FT /note="LRR 10"
FT REPEAT 306..328
FT /note="LRR 11"
FT REPEAT 329..350
FT /note="LRR 12"
FT REPEAT 353..374
FT /note="LRR 13"
FT REPEAT 375..396
FT /note="LRR 14"
FT REPEAT 399..420
FT /note="LRR 15"
FT REPEAT 423..446
FT /note="LRR 16"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23756651"
FT CARBOHYD 500
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 792
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..40
FT DISULFID 38..52
FT DISULFID 348..373
FT DISULFID 479..541
FT DISULFID 637..712
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 143..214
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_054782"
FT VAR_SEQ 263..286
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037746"
FT VARIANT 383
FT /note="H -> R (in dbSNP:rs12303775)"
FT /id="VAR_049411"
FT VARIANT 666
FT /note="V -> A (in dbSNP:rs17109924)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_049412"
FT MUTAGEN 146
FT /note="D->F: Abolishes activation of Wnt signaling."
FT /evidence="ECO:0000269|PubMed:23809763"
FT MUTAGEN 170
FT /note="D->F: Abolishes activation of Wnt signaling."
FT /evidence="ECO:0000269|PubMed:23809763"
FT MUTAGEN 190
FT /note="A->D: Abolishes activation of Wnt signaling."
FT /evidence="ECO:0000269|PubMed:23809763"
FT MUTAGEN 861
FT /note="S->A: Impaired internalization to the trans-Golgi
FT network; when associated with A-864."
FT /evidence="ECO:0000269|PubMed:23439653"
FT MUTAGEN 864
FT /note="S->A: Impaired internalization to the trans-Golgi
FT network; when associated with A-861."
FT /evidence="ECO:0000269|PubMed:23439653"
FT CONFLICT 90
FT /note="R -> H (in Ref. 2; AAC77911)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="L -> W (in Ref. 2; AAC77911)"
FT /evidence="ECO:0000305"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:4KNG"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:4UFR"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 107..112
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 133..136
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 155..160
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:4UFR"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 203..208
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 227..232
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:4UFR"
FT HELIX 251..255
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 274..279
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 298..303
FT /evidence="ECO:0007829|PDB:4KNG"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 331..338
FT /evidence="ECO:0007829|PDB:4UFR"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 391..396
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 415..420
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 446..449
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 462..464
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:4UFR"
FT HELIX 476..482
FT /evidence="ECO:0007829|PDB:4UFR"
FT HELIX 523..533
FT /evidence="ECO:0007829|PDB:4BSR"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:4BSR"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:4BSR"
SQ SEQUENCE 907 AA; 99998 MW; 822D5C5E6F0D9092 CRC64;
MDTSRLGVLL SLPVLLQLAT GGSSPRSGVL LRGCPTHCHC EPDGRMLLRV DCSDLGLSEL
PSNLSVFTSY LDLSMNNISQ LLPNPLPSLR FLEELRLAGN ALTYIPKGAF TGLYSLKVLM
LQNNQLRHVP TEALQNLRSL QSLRLDANHI SYVPPSCFSG LHSLRHLWLD DNALTEIPVQ
AFRSLSALQA MTLALNKIHH IPDYAFGNLS SLVVLHLHNN RIHSLGKKCF DGLHSLETLD
LNYNNLDEFP TAIRTLSNLK ELGFHSNNIR SIPEKAFVGN PSLITIHFYD NPIQFVGRSA
FQHLPELRTL TLNGASQITE FPDLTGTANL ESLTLTGAQI SSLPQTVCNQ LPNLQVLDLS
YNLLEDLPSF SVCQKLQKID LRHNEIYEIK VDTFQQLLSL RSLNLAWNKI AIIHPNAFST
LPSLIKLDLS SNLLSSFPIT GLHGLTHLKL TGNHALQSLI SSENFPELKV IEMPYAYQCC
AFGVCENAYK ISNQWNKGDN SSMDDLHKKD AGMFQAQDER DLEDFLLDFE EDLKALHSVQ
CSPSPGPFKP CEHLLDGWLI RIGVWTIAVL ALTCNALVTS TVFRSPLYIS PIKLLIGVIA
AVNMLTGVSS AVLAGVDAFT FGSFARHGAW WENGVGCHVI GFLSIFASES SVFLLTLAAL
ERGFSVKYSA KFETKAPFSS LKVIILLCAL LALTMAAVPL LGGSKYGASP LCLPLPFGEP
STMGYMVALI LLNSLCFLMM TIAYTKLYCN LDKGDLENIW DCSMVKHIAL LLFTNCILNC
PVAFLSFSSL INLTFISPEV IKFILLVVVP LPACLNPLLY ILFNPHFKED LVSLRKQTYV
WTRSKHPSLM SINSDDVEKQ SCDSTQALVT FTSSSITYDL PPSSVPSPAY PVTESCHLSS
VAFVPCL
