LGR4_HUMAN
ID LGR4_HUMAN Reviewed; 951 AA.
AC Q9BXB1; A6NCH3; G5E9B3; Q8N537; Q9NYD1;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 4;
DE AltName: Full=G-protein coupled receptor 48;
DE Flags: Precursor;
GN Name=LGR4; Synonyms=GPR48;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANTS GLY-215
RP AND SER-233.
RC TISSUE=Pancreas;
RX PubMed=11401528; DOI=10.1006/bbrc.2001.4625;
RA Loh E.D., Broussard S.R., Kolakowski L.F. Jr.;
RT "Molecular characterization of a novel glycoprotein hormone G-protein-
RT coupled receptor.";
RL Biochem. Biophys. Res. Commun. 282:757-764(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
RP FUNCTION.
RX PubMed=23444378; DOI=10.1242/jcs.123471;
RA Deng C., Reddy P., Cheng Y., Luo C.W., Hsiao C.L., Hsueh A.J.;
RT "Multi-functional norrin is a ligand for the LGR4 receptor.";
RL J. Cell Sci. 126:2060-2068(2013).
RN [10]
RP POLYMORPHISM, INVOLVEMENT IN OSTEOP, AND INVOLVEMENT IN BMND17.
RX PubMed=23644456; DOI=10.1038/nature12124;
RA Styrkarsdottir U., Thorleifsson G., Sulem P., Gudbjartsson D.F.,
RA Sigurdsson A., Jonasdottir A., Jonasdottir A., Oddsson A., Helgason A.,
RA Magnusson O.T., Walters G.B., Frigge M.L., Helgadottir H.T.,
RA Johannsdottir H., Bergsteinsdottir K., Ogmundsdottir M.H., Center J.R.,
RA Nguyen T.V., Eisman J.A., Christiansen C., Steingrimsson E., Jonasson J.G.,
RA Tryggvadottir L., Eyjolfsson G.I., Theodors A., Jonsson T., Ingvarsson T.,
RA Olafsson I., Rafnar T., Kong A., Sigurdsson G., Masson G.,
RA Thorsteinsdottir U., Stefansson K.;
RT "Nonsense mutation in the LGR4 gene is associated with several human
RT diseases and other traits.";
RL Nature 497:517-520(2013).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-920, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 26-527 IN COMPLEX WITH RSPO1,
RP FUNCTION, GLYCOSYLATION AT ASN-68 AND ASN-199, AND DISULFIDE BONDS.
RX PubMed=23756652; DOI=10.1101/gad.219360.113;
RA Wang D., Huang B., Zhang S., Yu X., Wu W., Wang X.;
RT "Structural basis for R-spondin recognition by LGR4/5/6 receptors.";
RL Genes Dev. 27:1339-1344(2013).
RN [13]
RP VARIANTS DPSL VAL-96; CYS-363 AND GLY-844, INVOLVEMENT IN DPSL, AND
RP CHARACTERIZATION OF VARIANTS DPSL VAL-96; CYS-363 AND GLY-844.
RX PubMed=32493844; DOI=10.1172/jci.insight.133434;
RA Mancini A., Howard S.R., Marelli F., Cabrera C.P., Barnes M.R.,
RA Sternberg M.J., Leprovots M., Hadjidemetriou I., Monti E., David A.,
RA Wehkalampi K., Oleari R., Lettieri A., Vezzoli V., Vassart G., Cariboni A.,
RA Bonomi M., Garcia M.I., Guasti L., Dunkel L.;
RT "LGR4 deficiency results in delayed puberty through impaired Wnt/beta-
RT catenin signaling.";
RL JCI Insight 5:0-0(2020).
CC -!- FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt
CC signaling pathway and is involved in the formation of various organs.
CC Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates
CC with phosphorylated LRP6 and frizzled receptors that are activated by
CC extracellular Wnt receptors, triggering the canonical Wnt signaling
CC pathway to increase expression of target genes. In contrast to
CC classical G-protein coupled receptors, does not activate heterotrimeric
CC G-proteins to transduce the signal. Its function as activator of the
CC Wnt signaling pathway is required for the development of various
CC organs, including liver, kidney, intestine, bone, reproductive tract
CC and eye. May also act as a receptor for norrin (NDP), such results
CC however require additional confirmation in vivo. Required during
CC spermatogenesis to activate the Wnt signaling pathway in peritubular
CC myoid cells. Required for the maintenance of intestinal stem cells and
CC Paneth cell differentiation in postnatal intestinal crypts. Acts as a
CC regulator of bone formation and remodeling. Involved in kidney
CC development; required for maintaining the ureteric bud in an
CC undifferentiated state. Involved in the development of the anterior
CC segment of the eye. Required during erythropoiesis. Also acts as a
CC negative regulator of innate immunity by inhibiting TLR2/TLR4
CC associated pattern-recognition and pro-inflammatory cytokine
CC production. Plays an important role in regulating the circadian rhythms
CC of plasma lipids, partially through regulating the rhythmic expression
CC of MTTP (By similarity). Required for proper development of GnRH
CC neurons (gonadotropin-releasing hormone expressing neurons) that
CC control the release of reproductive hormones from the pituitary gland
CC (By similarity). {ECO:0000250|UniProtKB:A2ARI4,
CC ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895,
CC ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22815884,
CC ECO:0000269|PubMed:23444378, ECO:0000269|PubMed:23756652}.
CC -!- INTERACTION:
CC Q9BXB1; Q9ULT6: ZNRF3; NbExp=2; IntAct=EBI-10965764, EBI-949772;
CC Q9BXB1-2; Q9P0N8: MARCHF2; NbExp=3; IntAct=EBI-17443382, EBI-10317612;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21693646,
CC ECO:0000269|PubMed:22815884}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:22815884}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BXB1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BXB1-2; Sequence=VSP_047136;
CC -!- TISSUE SPECIFICITY: Expressed in multiple steroidogenic tissues:
CC placenta, ovary, testis and adrenal. Expressed also in spinal cord,
CC thyroid, stomach, trachea, heart, pancreas, kidney, prostate and
CC spleen.
CC -!- POLYMORPHISM: Genetic variations in LGR4 define the bone mineral
CC density quantitative trait locus 17 (BMND17) [MIM:615311]. Variance in
CC bone mineral density influences bone mass, contributes to size
CC determination in the general population, and is a susceptibility factor
CC for osteoporotic fractures. {ECO:0000269|PubMed:23644456}.
CC -!- DISEASE: Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal
CC disorder characterized by decreased bone mass and deterioration of bone
CC microarchitecture without alteration in the composition of bone. The
CC result is fragile bones and an increased risk of fractures, even after
CC minimal trauma. Osteoporosis is a chronic condition of multifactorial
CC etiology and is usually clinically silent until a fracture occurs.
CC {ECO:0000269|PubMed:23644456}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC A LGR4 nonsense mutation creating a stop codon after position 126
CC (c.376C>T) is strongly associated with low bone mineral density and
CC osteoporotic fractures (PubMed:23644456). This mutation probably causes
CC degradation of the transcript by nonsense-mediated decay (NMD). The
CC c.376C>T mutation is also associated with electrolyte imbalance, late
CC onset of menarche and reduced testosterone levels, as well as an
CC increased risk of squamous cell carcinoma of the skin and biliary tract
CC cancer (PubMed:23644456). {ECO:0000269|PubMed:23644456}.
CC -!- DISEASE: Delayed puberty, self-limited (DPSL) [MIM:619613]: A condition
CC defined as the absence of testicular enlargement in boys or breast
CC development in girls at an age that is 2-2.5 SD later than the
CC population mean. DPSL is often familial and is highly heritable, most
CC commonly seen with an autosomal dominant inheritance pattern.
CC {ECO:0000269|PubMed:32493844}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF346711; AAK31153.1; -; Genomic_DNA.
DR EMBL; AF346709; AAK31153.1; JOINED; Genomic_DNA.
DR EMBL; AF346710; AAK31153.1; JOINED; Genomic_DNA.
DR EMBL; AF257182; AAF68989.1; -; mRNA.
DR EMBL; AC090597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC100771; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68285.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68286.1; -; Genomic_DNA.
DR EMBL; BC033039; AAH33039.1; -; mRNA.
DR CCDS; CCDS31449.1; -. [Q9BXB1-1]
DR CCDS; CCDS86187.1; -. [Q9BXB1-2]
DR RefSeq; NP_001333361.1; NM_001346432.1. [Q9BXB1-2]
DR RefSeq; NP_060960.2; NM_018490.3. [Q9BXB1-1]
DR PDB; 4KT1; X-ray; 2.50 A; A=26-527.
DR PDB; 4QXE; X-ray; 2.20 A; A=27-396.
DR PDB; 4QXF; X-ray; 2.25 A; A/B=27-252.
DR PDBsum; 4KT1; -.
DR PDBsum; 4QXE; -.
DR PDBsum; 4QXF; -.
DR AlphaFoldDB; Q9BXB1; -.
DR SMR; Q9BXB1; -.
DR BioGRID; 120644; 276.
DR CORUM; Q9BXB1; -.
DR DIP; DIP-59894N; -.
DR IntAct; Q9BXB1; 23.
DR STRING; 9606.ENSP00000368516; -.
DR GuidetoPHARMACOLOGY; 147; -.
DR GlyGen; Q9BXB1; 6 sites.
DR iPTMnet; Q9BXB1; -.
DR PhosphoSitePlus; Q9BXB1; -.
DR BioMuta; LGR4; -.
DR DMDM; 212286375; -.
DR EPD; Q9BXB1; -.
DR jPOST; Q9BXB1; -.
DR MassIVE; Q9BXB1; -.
DR MaxQB; Q9BXB1; -.
DR PaxDb; Q9BXB1; -.
DR PeptideAtlas; Q9BXB1; -.
DR PRIDE; Q9BXB1; -.
DR ProteomicsDB; 33888; -.
DR ProteomicsDB; 79397; -. [Q9BXB1-1]
DR ABCD; Q9BXB1; 2 sequenced antibodies.
DR Antibodypedia; 12720; 434 antibodies from 33 providers.
DR DNASU; 55366; -.
DR Ensembl; ENST00000379214.9; ENSP00000368516.4; ENSG00000205213.14. [Q9BXB1-1]
DR Ensembl; ENST00000389858.4; ENSP00000374508.4; ENSG00000205213.14. [Q9BXB1-2]
DR GeneID; 55366; -.
DR KEGG; hsa:55366; -.
DR MANE-Select; ENST00000379214.9; ENSP00000368516.4; NM_018490.5; NP_060960.2.
DR UCSC; uc001mrj.5; human. [Q9BXB1-1]
DR CTD; 55366; -.
DR DisGeNET; 55366; -.
DR GeneCards; LGR4; -.
DR HGNC; HGNC:13299; LGR4.
DR HPA; ENSG00000205213; Low tissue specificity.
DR MalaCards; LGR4; -.
DR MIM; 166710; phenotype.
DR MIM; 606666; gene.
DR MIM; 615311; phenotype.
DR MIM; 619613; phenotype.
DR neXtProt; NX_Q9BXB1; -.
DR OpenTargets; ENSG00000205213; -.
DR PharmGKB; PA28893; -.
DR VEuPathDB; HostDB:ENSG00000205213; -.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000157925; -.
DR HOGENOM; CLU_006843_0_0_1; -.
DR InParanoid; Q9BXB1; -.
DR OMA; DLFWMCL; -.
DR OrthoDB; 1095345at2759; -.
DR PhylomeDB; Q9BXB1; -.
DR TreeFam; TF316814; -.
DR PathwayCommons; Q9BXB1; -.
DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination.
DR SignaLink; Q9BXB1; -.
DR SIGNOR; Q9BXB1; -.
DR BioGRID-ORCS; 55366; 13 hits in 1080 CRISPR screens.
DR ChiTaRS; LGR4; human.
DR GeneWiki; LGR4; -.
DR GenomeRNAi; 55366; -.
DR Pharos; Q9BXB1; Tbio.
DR PRO; PR:Q9BXB1; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BXB1; protein.
DR Bgee; ENSG00000205213; Expressed in adrenal tissue and 198 other tissues.
DR ExpressionAtlas; Q9BXB1; baseline and differential.
DR Genevisible; Q9BXB1; 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: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:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB.
DR GO; GO:0061290; P:canonical Wnt signaling pathway involved in metanephric kidney development; IEA:Ensembl.
DR GO; GO:0072202; P:cell differentiation involved in metanephros development; IEA:Ensembl.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl.
DR GO; GO:2001013; P:epithelial cell proliferation involved in renal tubule morphogenesis; IEA:Ensembl.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; IEA:Ensembl.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0072224; P:metanephric glomerulus development; IEA:Ensembl.
DR GO; GO:0072282; P:metanephric nephron tubule morphogenesis; IEA:Ensembl.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
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; PF00001; 7tm_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; Biological rhythms; Cell membrane;
KW Developmental protein; Differentiation; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Immunity; Innate immunity;
KW Leucine-rich repeat; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Spermatogenesis; Transducer;
KW Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..951
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 4"
FT /id="PRO_0000012792"
FT TOPO_DOM 25..544
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..565
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..596
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..620
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 621..641
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 642..661
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 662..682
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 683..703
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 704..724
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 725..756
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 757..777
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 778..783
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 784..804
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 805..951
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..57
FT /note="LRRNT"
FT REPEAT 58..79
FT /note="LRR 1"
FT REPEAT 82..103
FT /note="LRR 2"
FT REPEAT 106..127
FT /note="LRR 3"
FT REPEAT 130..151
FT /note="LRR 4"
FT REPEAT 154..177
FT /note="LRR 5"
FT REPEAT 178..199
FT /note="LRR 6"
FT REPEAT 202..223
FT /note="LRR 7"
FT REPEAT 226..247
FT /note="LRR 8"
FT REPEAT 249..270
FT /note="LRR 9"
FT REPEAT 273..294
FT /note="LRR 10"
FT REPEAT 320..341
FT /note="LRR 11"
FT REPEAT 344..365
FT /note="LRR 12"
FT REPEAT 366..387
FT /note="LRR 13"
FT REPEAT 390..411
FT /note="LRR 14"
FT REPEAT 414..435
FT /note="LRR 15"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23756652"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23756652"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..35
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:23756652"
FT DISULFID 33..43
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:23756652"
FT DISULFID 339..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:23756652"
FT DISULFID 470..522
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:23756652"
FT DISULFID 471..476
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:23756652"
FT DISULFID 618..693
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 62..85
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047136"
FT VARIANT 96
FT /note="I -> V (in DPSL; unknown pathological significance;
FT when transfected in HEK293T cells it results in slightly
FT reduced WNT signaling; decreased protein expression in
FT transfected cells)"
FT /evidence="ECO:0000269|PubMed:32493844"
FT /id="VAR_086463"
FT VARIANT 215
FT /note="S -> G (in dbSNP:rs2448010)"
FT /evidence="ECO:0000269|PubMed:11401528"
FT /id="VAR_044528"
FT VARIANT 233
FT /note="N -> S (in dbSNP:rs2472617)"
FT /evidence="ECO:0000269|PubMed:11401528"
FT /id="VAR_044529"
FT VARIANT 363
FT /note="G -> C (in DPSL; unknown pathological significance;
FT when transfected in HEK293T cells it results in slightly
FT reduced WNT signaling; decreased protein expression in
FT transfected cells)"
FT /evidence="ECO:0000269|PubMed:32493844"
FT /id="VAR_086464"
FT VARIANT 480
FT /note="A -> V (in dbSNP:rs12284579)"
FT /id="VAR_044530"
FT VARIANT 684
FT /note="R -> G (in dbSNP:rs7125959)"
FT /id="VAR_044531"
FT VARIANT 709
FT /note="T -> M (in dbSNP:rs34717439)"
FT /id="VAR_044532"
FT VARIANT 844
FT /note="D -> G (in DPSL; unknown pathological significance;
FT when transfected in HEK293T cells has no effect on WNT
FT signaling; decreased protein expression in transfected
FT cells; dbSNP:rs34804482)"
FT /evidence="ECO:0000269|PubMed:32493844"
FT /id="VAR_044533"
FT CONFLICT 22
FT /note="S -> G (in Ref. 4; AAH33039)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="P -> H (in Ref. 4; AAH33039)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="L -> R (in Ref. 1; AAF68989/AAK31153)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="F -> S (in Ref. 1; AAF68989)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="L -> P (in Ref. 1; AAF68989)"
FT /evidence="ECO:0000305"
FT CONFLICT 668
FT /note="L -> S (in Ref. 1; AAF68989)"
FT /evidence="ECO:0000305"
FT CONFLICT 681
FT /note="L -> I (in Ref. 4; AAH33039)"
FT /evidence="ECO:0000305"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 74..79
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 98..103
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 122..127
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 146..151
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:4QXE"
FT HELIX 170..173
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 194..199
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 218..223
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:4QXE"
FT HELIX 242..246
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 265..270
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 289..294
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 323..329
FT /evidence="ECO:0007829|PDB:4QXE"
FT HELIX 338..341
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 342..344
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:4QXE"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 382..387
FT /evidence="ECO:0007829|PDB:4KT1"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:4QXE"
FT TURN 406..411
FT /evidence="ECO:0007829|PDB:4KT1"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:4KT1"
FT STRAND 437..440
FT /evidence="ECO:0007829|PDB:4KT1"
FT HELIX 453..456
FT /evidence="ECO:0007829|PDB:4KT1"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:4KT1"
FT HELIX 467..470
FT /evidence="ECO:0007829|PDB:4KT1"
FT TURN 471..473
FT /evidence="ECO:0007829|PDB:4KT1"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:4KT1"
SQ SEQUENCE 951 AA; 104475 MW; 42D48AE5F0BEB6B1 CRC64;
MPGPLGLLCF LALGLLGSAG PSGAAPPLCA APCSCDGDRR VDCSGKGLTA VPEGLSAFTQ
ALDISMNNIT QLPEDAFKNF PFLEELQLAG NDLSFIHPKA LSGLKELKVL TLQNNQLKTV
PSEAIRGLSA LQSLRLDANH ITSVPEDSFE GLVQLRHLWL DDNSLTEVPV HPLSNLPTLQ
ALTLALNKIS SIPDFAFTNL SSLVVLHLHN NKIRSLSQHC FDGLDNLETL DLNYNNLGEF
PQAIKALPSL KELGFHSNSI SVIPDGAFDG NPLLRTIHLY DNPLSFVGNS AFHNLSDLHS
LVIRGASMVQ QFPNLTGTVH LESLTLTGTK ISSIPNNLCQ EQKMLRTLDL SYNNIRDLPS
FNGCHALEEI SLQRNQIYQI KEGTFQGLIS LRILDLSRNL IHEIHSRAFA TLGPITNLDV
SFNELTSFPT EGLNGLNQLK LVGNFKLKEA LAAKDFVNLR SLSVPYAYQC CAFWGCDSYA
NLNTEDNSLQ DHSVAQEKGT ADAANVTSTL ENEEHSQIII HCTPSTGAFK PCEYLLGSWM
IRLTVWFIFL VALFFNLLVI LTTFASCTSL PSSKLFIGLI SVSNLFMGIY TGILTFLDAV
SWGRFAEFGI WWETGSGCKV AGFLAVFSSE SAIFLLMLAT VERSLSAKDI MKNGKSNHLK
QFRVAALLAF LGATVAGCFP LFHRGEYSAS PLCLPFPTGE TPSLGFTVTL VLLNSLAFLL
MAVIYTKLYC NLEKEDLSEN SQSSMIKHVA WLIFTNCIFF CPVAFFSFAP LITAISISPE
IMKSVTLIFF PLPACLNPVL YVFFNPKFKE DWKLLKRRVT KKSGSVSVSI SSQGGCLEQD
FYYDCGMYSH LQGNLTVCDC CESFLLTKPV SCKHLIKSHS CPALAVASCQ RPEGYWSDCG
TQSAHSDYAD EEDSFVSDSS DQVQACGRAC FYQSRGFPLV RYAYNLPRVK D
