ID RSPO2_HUMAN Reviewed; 243 AA. AC Q6UXX9; B3KVP0; Q4G0U4; Q8N6X6; DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 15-MAY-2007, sequence version 2. DT 24-JAN-2024, entry version 152. DE RecName: Full=R-spondin-2; DE AltName: Full=Roof plate-specific spondin-2; DE Short=hRspo2; DE Flags: Precursor; GN Name=RSPO2; ORFNames=UNQ9384/PRO34209; 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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-186. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-186. RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-186. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT RP PRO-186. RC TISSUE=Lung, and Testis; 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 FUNCTION, AND INTERACTION WITH LGR4 AND LGR5. 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 [7] RP FUNCTION, AND INTERACTION WITH LGR4; LGR5 AND LGR6. 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 [8] RP FUNCTION, AND INTERACTION WITH LGR6. RX PubMed=22615920; DOI=10.1371/journal.pone.0037137; RA Gong X., Carmon K.S., Lin Q., Thomas A., Yi J., Liu Q.; RT "LGR6 is a high affinity receptor of R-spondins and potentially functions RT as a tumor suppressor."; RL PLoS ONE 7:E37137-E37137(2012). RN [9] RP INVOLVEMENT IN TETAMS2, VARIANTS TETAMS2 70-GLN--GLN-243 DEL AND RP 137-GLU--GLN-243 DEL, INVOLVEMENT IN HHRRD, VARIANT HHRRD CYS-69, RP CHARACTERIZATION OF VARIANT TETAMS2 70-GLN--GLN-243, CHARACTERIZATION OF RP VARIANT HHRRD CYS-69, FUNCTION, INTERACTION WITH LGR5; RNF43 AND ZNRF3, AND RP MUTAGENESIS OF PHE-105 AND PHE-109. 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). CC -!- FUNCTION: Activator of the canonical Wnt signaling pathway by acting as CC a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or CC LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors CC that are activated by extracellular Wnt receptors, triggering the CC canonical Wnt signaling pathway to increase expression of target genes. CC Also regulates the canonical Wnt/beta-catenin-dependent pathway and CC non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an CC important regulator of the Wnt signaling pathway (PubMed:21909076, CC PubMed:21727895, PubMed:22615920). During embryonic development, plays CC a crucial role in limb specification, amplifying the Wnt signaling CC pathway independently of LGR4-6 receptors, possibly by acting as a CC direct antagonistic ligand to RNF43 and ZNRF3, hence governing the CC number of limbs an embryo should form (PubMed:29769720). CC {ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, CC ECO:0000269|PubMed:22615920, ECO:0000269|PubMed:29769720}. CC -!- SUBUNIT: Interacts with WNT1 (By similarity). Binds heparin (By CC similarity). Interacts with LGR4, LGR5 and LGR6 (PubMed:21909076, CC PubMed:21727895, PubMed:22615920, PubMed:29769720). Interacts with E3 CC ubiquitin ligases RNF43 and ZNRF3 (PubMed:29769720). CC {ECO:0000250|UniProtKB:Q8BFU0, ECO:0000269|PubMed:21727895, CC ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22615920, CC ECO:0000269|PubMed:29769720}. CC -!- INTERACTION: CC Q6UXX9; P60372: KRTAP10-4; NbExp=3; IntAct=EBI-8481036, EBI-10178153; CC Q6UXX9; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-8481036, EBI-10172290; CC Q6UXX9; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-8481036, EBI-10172052; CC Q6UXX9; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-8481036, EBI-742388; CC Q6UXX9-2; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-12009390, EBI-744545; CC Q6UXX9-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12009390, EBI-3867333; CC Q6UXX9-2; P49639: HOXA1; NbExp=3; IntAct=EBI-12009390, EBI-740785; CC Q6UXX9-2; P60371: KRTAP10-6; NbExp=3; IntAct=EBI-12009390, EBI-12012928; CC Q6UXX9-2; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-12009390, EBI-10172290; CC Q6UXX9-2; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-12009390, EBI-11953334; CC Q6UXX9-2; Q92504: SLC39A7; NbExp=3; IntAct=EBI-12009390, EBI-1051105; CC Q6UXX9-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12009390, EBI-5235340; CC Q6UXX9-2; Q9Y3S2: ZNF330; NbExp=3; IntAct=EBI-12009390, EBI-373456; CC Q6UXX9-2; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-12009390, EBI-11962574; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8BFU0}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6UXX9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6UXX9-2; Sequence=VSP_018321; CC Name=3; CC IsoId=Q6UXX9-3; Sequence=VSP_018322, VSP_018323; CC -!- DOMAIN: The FU repeat is required for activation and stabilization of CC beta-catenin. {ECO:0000250}. CC -!- DISEASE: Tetraamelia syndrome 2 (TETAMS2) [MIM:618021]: A form of CC tetraamelia, a rare disease characterized by rudimentary appendages or CC complete absence of all four limbs, and other anomalies such as CC craniofacial, nervous system, pulmonary, skeletal and urogenital CC defects. TETAMS2 patients manifest limb deformities, bilateral agenesis CC of the lungs, abnormalities of the pulmonary vasculature, labioscrotal CC fold aplasia, and dysmorphic features including bilateral cleft CC lip/palate, ankyloglossia, mandibular hypoplasia, and CC microretrognathia. TETAMS2 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:29769720}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Humerofemoral hypoplasia with radiotibial ray deficiency CC (HHRRD) [MIM:618022]: A severe disease characterized by reduction of CC all four limbs as well as hypoplasia of the upper limb girdle and CC pelvis. Rudimentary finger- or toe-like appendages may be present. CC HHRRD transmission pattern is consistent with autosomal recessive CC inheritance. {ECO:0000269|PubMed:29769720}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the R-spondin family. {ECO:0000305}. 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; AY358166; AAQ88533.1; -; mRNA. DR EMBL; AK123023; BAG53852.1; -; mRNA. DR EMBL; AC025508; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP003479; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW91916.1; -; Genomic_DNA. DR EMBL; BC027938; AAH27938.1; -; mRNA. DR EMBL; BC036554; AAH36554.1; -; mRNA. DR CCDS; CCDS6307.1; -. [Q6UXX9-1] DR CCDS; CCDS64953.1; -. [Q6UXX9-3] DR CCDS; CCDS83314.1; -. [Q6UXX9-2] DR RefSeq; NP_001269792.1; NM_001282863.1. [Q6UXX9-3] DR RefSeq; NP_001304871.1; NM_001317942.1. [Q6UXX9-2] DR RefSeq; NP_848660.3; NM_178565.4. [Q6UXX9-1] DR AlphaFoldDB; Q6UXX9; -. DR SMR; Q6UXX9; -. DR BioGRID; 131049; 22. DR IntAct; Q6UXX9; 16. DR MINT; Q6UXX9; -. DR STRING; 9606.ENSP00000276659; -. DR GlyCosmos; Q6UXX9; 1 site, No reported glycans. DR GlyGen; Q6UXX9; 1 site. DR PhosphoSitePlus; Q6UXX9; -. DR BioMuta; RSPO2; -. DR DMDM; 147744588; -. DR PaxDb; 9606-ENSP00000276659; -. DR PeptideAtlas; Q6UXX9; -. DR ProteomicsDB; 67672; -. [Q6UXX9-1] DR ProteomicsDB; 67673; -. [Q6UXX9-2] DR ProteomicsDB; 67674; -. [Q6UXX9-3] DR Antibodypedia; 26506; 154 antibodies from 25 providers. DR DNASU; 340419; -. DR Ensembl; ENST00000276659.10; ENSP00000276659.5; ENSG00000147655.12. [Q6UXX9-1] DR Ensembl; ENST00000517781.5; ENSP00000427937.1; ENSG00000147655.12. [Q6UXX9-3] DR Ensembl; ENST00000517939.5; ENSP00000428940.1; ENSG00000147655.12. [Q6UXX9-2] DR GeneID; 340419; -. DR KEGG; hsa:340419; -. DR MANE-Select; ENST00000276659.10; ENSP00000276659.5; NM_178565.5; NP_848660.3. DR UCSC; uc003ymq.4; human. [Q6UXX9-1] DR AGR; HGNC:28583; -. DR CTD; 340419; -. DR DisGeNET; 340419; -. DR GeneCards; RSPO2; -. DR HGNC; HGNC:28583; RSPO2. DR HPA; ENSG00000147655; Tissue enhanced (brain, intestine, placenta). DR MalaCards; RSPO2; -. DR MIM; 610575; gene. DR MIM; 618021; phenotype. DR MIM; 618022; phenotype. DR neXtProt; NX_Q6UXX9; -. DR OpenTargets; ENSG00000147655; -. DR Orphanet; 3301; Tetraamelia-multiple malformations syndrome. DR PharmGKB; PA142670968; -. DR VEuPathDB; HostDB:ENSG00000147655; -. DR eggNOG; KOG3525; Eukaryota. DR GeneTree; ENSGT00940000159194; -. DR HOGENOM; CLU_064219_1_0_1; -. DR InParanoid; Q6UXX9; -. DR OMA; HGECLHA; -. DR OrthoDB; 196918at2759; -. DR PhylomeDB; Q6UXX9; -. DR TreeFam; TF331799; -. DR PathwayCommons; Q6UXX9; -. DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination. DR SignaLink; Q6UXX9; -. DR SIGNOR; Q6UXX9; -. DR BioGRID-ORCS; 340419; 13 hits in 1146 CRISPR screens. DR ChiTaRS; RSPO2; human. DR GeneWiki; RSPO2; -. DR GenomeRNAi; 340419; -. DR Pharos; Q6UXX9; Tbio. DR PRO; PR:Q6UXX9; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q6UXX9; Protein. DR Bgee; ENSG00000147655; Expressed in secondary oocyte and 108 other cell types or tissues. DR ExpressionAtlas; Q6UXX9; baseline and differential. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl. DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl. DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEA:Ensembl. DR GO; GO:0060173; P:limb development; IMP:UniProtKB. DR GO; GO:0060437; P:lung growth; IEA:Ensembl. DR GO; GO:0042489; P:negative regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0060535; P:trachea cartilage morphogenesis; IEA:Ensembl. DR CDD; cd00064; FU; 1. DR Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 1. DR InterPro; IPR006212; Furin_repeat. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR043601; Rspo_Fu-CRD_dom. DR InterPro; IPR000884; TSP1_rpt. DR InterPro; IPR036383; TSP1_rpt_sf. DR PANTHER; PTHR46987; NEUROHYPOPHYSIAL HORMONES, N-TERMINAL DOMAIN CONTAINING PROTEIN; 1. DR PANTHER; PTHR46987:SF4; R-SPONDIN-2; 1. DR Pfam; PF15913; Furin-like_2; 1. DR SMART; SM00261; FU; 2. DR SMART; SM00209; TSP1; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF82895; TSP-1 type 1 repeat; 1. DR PROSITE; PS50092; TSP1; 1. DR Genevisible; Q6UXX9; HS. PE 1: Evidence at protein level; KW Alternative splicing; Developmental protein; Disease variant; KW Disulfide bond; Glycoprotein; Heparin-binding; Reference proteome; KW Secreted; Sensory transduction; Signal; Wnt signaling pathway. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..243 FT /note="R-spondin-2" FT /id="PRO_0000234439" FT REPEAT 90..134 FT /note="FU" FT DOMAIN 144..204 FT /note="TSP type-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT REGION 204..243 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 204..223 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 40..46 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 43..52 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 55..74 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 78..93 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 96..104 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 101..110 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 113..124 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 128..141 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 145..187 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 156..163 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 196..203 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT VAR_SEQ 1..67 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_018321" FT VAR_SEQ 32..95 FT /note="ASYVSNPICKGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYY FT GHRAPDMNRCAR -> G (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_018322" FT VAR_SEQ 143 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_018323" FT VARIANT 69 FT /note="R -> C (in HHRRD; loss of LGR5-, RNF43- and FT ZNRF3-binding; decreased ability to amplify WNT3A FT signaling; dbSNP:rs758888137)" FT /evidence="ECO:0000269|PubMed:29769720" FT /id="VAR_081036" FT VARIANT 70..243 FT /note="Missing (in TETAMS2; loss of LGR5-, RNF43- and FT ZNRF3-binding; complete loss of amplification of WNT3A FT signaling)" FT /evidence="ECO:0000269|PubMed:29769720" FT /id="VAR_081037" FT VARIANT 137..243 FT /note="Missing (in TETAMS2)" FT /evidence="ECO:0000269|PubMed:29769720" FT /id="VAR_081038" FT VARIANT 186 FT /note="L -> P (in dbSNP:rs601558)" FT /evidence="ECO:0000269|PubMed:12975309, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.4" FT /id="VAR_026247" FT MUTAGEN 105 FT /note="F->A: Loss of LGR5-binding, no effect on interaction FT with RNF43 and ZNRF3, no effect on WNT3A signaling; when FT associated with A-109." FT /evidence="ECO:0000269|PubMed:29769720" FT MUTAGEN 109 FT /note="F->A: Loss of LGR5-binding, no effect on interaction FT with RNF43 and ZNRF3, no effect on WNT3A signaling; when FT associated with A-105." FT /evidence="ECO:0000269|PubMed:29769720" SQ SEQUENCE 243 AA; 28315 MW; 96F44F105B21BB52 CRC64; MQFRLFSFAL IILNCMDYSH CQGNRWRRSK RASYVSNPIC KGCLSCSKDN GCSRCQQKLF FFLRREGMRQ YGECLHSCPS GYYGHRAPDM NRCARCRIEN CDSCFSKDFC TKCKVGFYLH RGRCFDECPD GFAPLEETME CVEGCEVGHW SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP VKDTILCPTI AESRRCKMTM RHCPGGKRTP KAKEKRNKKK KRKLIERAQE QHSVFLATDR ANQ //