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 13-FEB-2019, entry version 171. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT the 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., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA 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., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA 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., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., 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 RT project: 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., RA Black S., 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., RA Ingelfinger D., 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., RA Kujala P., Haegebarth A., Peters P.J., van de Wetering M., RA Stange D.E., van Es J.E., Guardavaccaro D., Schasfoort R.B., Mohri Y., RA Nishimori K., Mohammed S., 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; RP RSPO3 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 RT to 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., RA Zhang Y., Hao H., Shi X., Liu D., Song Q., Clay I., Hintzen G., RA Tchorz J., Bouchez L.C., Michaud G., Finan P., Myer V.E., RA Bouwmeester T., Porter J., Hild M., Bassilana F., Parker C.N., RA Cong F.; RT "R-Spondin potentiates Wnt/beta-catenin signaling through orphan RT receptors 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., RA Khatoo M., Thi Tran H., Naert T., Noelanders R., Hajamohideen A., RA Beneteau C., de Sousa S.B., Karaman B., Latypova X., Basaran S., RA Yuecel E.B., Tan T.T., Vlaminck L., Nayak S.S., Shukla A., RA Girisha K.M., Le Caignec C., Soshnikova N., Uyguner Z.O., RA Vleminckx K., Barker N., Kayserili H., Reversade B.; RT "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development RT independently 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 RP 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., RA Clevers H., 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 RP AND 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 CC Wnt signaling pathway and acts as a stem cell marker of the CC intestinal epithelium and the hair follicle. Upon binding to R- CC spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with CC phosphorylated LRP6 and frizzled receptors that are activated by CC extracellular Wnt receptors, triggering the canonical Wnt CC signaling pathway to increase expression of target genes. In CC contrast to classical G-protein coupled receptors, does not CC activate heterotrimeric G-proteins to transduce the signal. CC Involved in the development and/or maintenance of the adult CC intestinal 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, CC PubMed:22815884, PubMed:23809763, PubMed:23756651). Also interacts CC with other R-spondin ligands, including RSPO2, RSPO3 and RSPO4 CC (PubMed:21909076, PubMed:21727895, PubMed:21693646, CC PubMed:29769720). {ECO:0000269|PubMed:21693646, CC ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, CC ECO:0000269|PubMed:22815884, ECO:0000269|PubMed:23756651, CC ECO:0000269|PubMed:23809763, ECO:0000269|PubMed:29769720}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane CC protein. Note=Rapidly and constitutively internalized to the CC trans-Golgi network at steady state. Internalization to the trans- CC Golgi network may be the result of phosphorylation at Ser-861 and CC Ser-864; however, the phosphorylation event has not been proven CC (PubMed:23439653). {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 CC in colonic and small mucosa stem cells. In premalignant cancer CC expression is not restricted to the cript base. Overexpressed in CC cancers of the ovary, colon and liver. CC {ECO:0000269|PubMed:12601349, ECO:0000269|PubMed:16575208, CC ECO:0000269|PubMed:19030762}. CC -!- MISCELLANEOUS: LGR5 is used as a marker of adult tissue stem cells CC in 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}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 UniGene; Hs.658889; -. 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 ProteinModelPortal; O75473; -. DR SMR; O75473; -. DR BioGrid; 114119; 7. DR CORUM; O75473; -. DR STRING; 9606.ENSP00000266674; -. DR GuidetoPHARMACOLOGY; 148; -. DR iPTMnet; O75473; -. DR PhosphoSitePlus; O75473; -. DR BioMuta; LGR5; -. DR jPOST; O75473; -. DR MaxQB; O75473; -. DR PaxDb; O75473; -. DR PeptideAtlas; O75473; -. DR PRIDE; O75473; -. DR ProteomicsDB; 50034; -. DR ProteomicsDB; 50035; -. [O75473-2] DR Ensembl; ENST00000266674; ENSP00000266674; ENSG00000139292. [O75473-1] DR Ensembl; ENST00000536515; ENSP00000443033; ENSG00000139292. [O75473-3] DR Ensembl; ENST00000540815; ENSP00000441035; ENSG00000139292. [O75473-2] DR GeneID; 8549; -. DR KEGG; hsa:8549; -. DR UCSC; uc001swl.5; human. [O75473-1] DR CTD; 8549; -. DR DisGeNET; 8549; -. DR EuPathDB; HostDB:ENSG00000139292.12; -. DR GeneCards; LGR5; -. DR HGNC; HGNC:4504; LGR5. DR HPA; HPA012530; -. DR MIM; 606667; gene. DR neXtProt; NX_O75473; -. DR OpenTargets; ENSG00000139292; -. DR PharmGKB; PA28894; -. DR eggNOG; KOG0619; Eukaryota. DR eggNOG; KOG2087; Eukaryota. DR eggNOG; COG4886; LUCA. DR GeneTree; ENSGT00940000160214; -. DR HOGENOM; HOG000231829; -. DR HOVERGEN; HBG031675; -. DR InParanoid; O75473; -. DR KO; K04308; -. DR OMA; KCSAKFE; -. DR OrthoDB; 340670at2759; -. DR PhylomeDB; O75473; -. DR TreeFam; TF316814; -. DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination. DR SIGNOR; O75473; -. DR ChiTaRS; LGR5; human. DR GeneWiki; LGR5; -. DR GenomeRNAi; 8549; -. DR PRO; PR:O75473; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000139292; Expressed in 162 organ(s), highest expression level in endometrium. DR ExpressionAtlas; O75473; baseline and differential. DR Genevisible; O75473; HS. DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central. 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:0007190; P:activation of adenylate cyclase activity; IBA:GO_Central. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central. 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:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central. 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; Complete proteome; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; KW Golgi apparatus; Leucine-rich repeat; Membrane; Polymorphism; KW Receptor; Reference proteome; Repeat; Signal; Transducer; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 907 Leucine-rich repeat-containing G-protein FT coupled receptor 5. FT /FTId=PRO_0000012794. FT TOPO_DOM 22 561 Extracellular. {ECO:0000255}. FT TRANSMEM 562 582 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 583 593 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 594 614 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 615 638 Extracellular. {ECO:0000255}. FT TRANSMEM 639 659 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 660 682 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 683 703 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 704 722 Extracellular. {ECO:0000255}. FT TRANSMEM 723 743 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 744 767 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 768 788 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 789 802 Extracellular. {ECO:0000255}. FT TRANSMEM 803 823 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 824 907 Cytoplasmic. {ECO:0000255}. FT DOMAIN 25 66 LRRNT. FT REPEAT 67 90 LRR 1. FT REPEAT 91 112 LRR 2. FT REPEAT 115 136 LRR 3. FT REPEAT 139 160 LRR 4. FT REPEAT 163 184 LRR 5. FT REPEAT 187 208 LRR 6. FT REPEAT 211 232 LRR 7. FT REPEAT 235 256 LRR 8. FT REPEAT 258 279 LRR 9. FT REPEAT 282 303 LRR 10. FT REPEAT 306 328 LRR 11. FT REPEAT 329 350 LRR 12. FT REPEAT 353 374 LRR 13. FT REPEAT 375 396 LRR 14. FT REPEAT 399 420 LRR 15. FT REPEAT 423 446 LRR 16. FT CARBOHYD 63 63 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 77 77 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 208 208 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:23756651}. FT CARBOHYD 500 500 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 792 792 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 34 40 FT DISULFID 38 52 FT DISULFID 348 373 FT DISULFID 479 541 FT DISULFID 637 712 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT VAR_SEQ 143 214 Missing (in isoform 3). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_054782. FT VAR_SEQ 263 286 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_037746. FT VARIANT 383 383 H -> R (in dbSNP:rs12303775). FT /FTId=VAR_049411. FT VARIANT 666 666 V -> A (in dbSNP:rs17109924). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_049412. FT MUTAGEN 146 146 D->F: Abolishes activation of Wnt FT signaling. {ECO:0000269|PubMed:23809763}. FT MUTAGEN 170 170 D->F: Abolishes activation of Wnt FT signaling. {ECO:0000269|PubMed:23809763}. FT MUTAGEN 190 190 A->D: Abolishes activation of Wnt FT signaling. {ECO:0000269|PubMed:23809763}. FT MUTAGEN 861 861 S->A: Impaired internalization to the FT trans-Golgi network; when associated with FT A-864. {ECO:0000269|PubMed:23439653}. FT MUTAGEN 864 864 S->A: Impaired internalization to the FT trans-Golgi network; when associated with FT A-861. {ECO:0000269|PubMed:23439653}. FT CONFLICT 90 90 R -> H (in Ref. 2; AAC77911). FT {ECO:0000305}. FT CONFLICT 212 212 L -> W (in Ref. 2; AAC77911). FT {ECO:0000305}. FT STRAND 39 42 {ECO:0000244|PDB:4UFR}. FT TURN 44 46 {ECO:0000244|PDB:4KNG}. FT STRAND 48 51 {ECO:0000244|PDB:4UFR}. FT STRAND 68 72 {ECO:0000244|PDB:4KNG}. FT STRAND 94 96 {ECO:0000244|PDB:4KNG}. FT TURN 107 112 {ECO:0000244|PDB:4KNG}. FT STRAND 118 120 {ECO:0000244|PDB:4KNG}. FT TURN 133 136 {ECO:0000244|PDB:4KNG}. FT STRAND 141 144 {ECO:0000244|PDB:4UFR}. FT HELIX 158 160 {ECO:0000244|PDB:4UFR}. FT STRAND 166 168 {ECO:0000244|PDB:4UFR}. FT TURN 179 184 {ECO:0000244|PDB:4UFR}. FT STRAND 190 192 {ECO:0000244|PDB:4UFR}. FT TURN 205 208 {ECO:0000244|PDB:4UFR}. FT STRAND 214 216 {ECO:0000244|PDB:4UFR}. FT TURN 227 232 {ECO:0000244|PDB:4UFR}. FT STRAND 238 240 {ECO:0000244|PDB:4UFR}. FT HELIX 252 254 {ECO:0000244|PDB:4UFR}. FT STRAND 261 263 {ECO:0000244|PDB:4UFR}. FT TURN 274 279 {ECO:0000244|PDB:4UFR}. FT STRAND 285 287 {ECO:0000244|PDB:4UFR}. FT TURN 298 303 {ECO:0000244|PDB:4UFR}. FT STRAND 309 311 {ECO:0000244|PDB:4UFR}. FT HELIX 323 327 {ECO:0000244|PDB:4UFR}. FT STRAND 332 334 {ECO:0000244|PDB:4UFR}. FT TURN 345 350 {ECO:0000244|PDB:4UFR}. FT STRAND 356 358 {ECO:0000244|PDB:4UFR}. FT STRAND 380 385 {ECO:0000244|PDB:4UFR}. FT TURN 393 396 {ECO:0000244|PDB:4KNG}. FT STRAND 401 408 {ECO:0000244|PDB:4UFR}. FT HELIX 417 420 {ECO:0000244|PDB:4UFR}. FT STRAND 426 428 {ECO:0000244|PDB:4UFR}. FT TURN 441 444 {ECO:0000244|PDB:4UFR}. FT STRAND 446 449 {ECO:0000244|PDB:4UFR}. FT TURN 462 467 {ECO:0000244|PDB:4UFR}. FT STRAND 470 472 {ECO:0000244|PDB:4KNG}. FT TURN 476 478 {ECO:0000244|PDB:4KNG}. FT HELIX 480 482 {ECO:0000244|PDB:4BSR}. FT TURN 486 491 {ECO:0000244|PDB:4UFR}. FT STRAND 497 499 {ECO:0000244|PDB:4UFR}. FT TURN 522 524 {ECO:0000244|PDB:4UFR}. FT STRAND 535 537 {ECO:0000244|PDB:4UFR}. FT HELIX 538 543 {ECO:0000244|PDB:4UFR}. 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 //