RSPO2_HUMAN
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 03-AUG-2022, entry version 145.
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}.
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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; 21.
DR IntAct; Q6UXX9; 16.
DR MINT; Q6UXX9; -.
DR STRING; 9606.ENSP00000276659; -.
DR GlyGen; Q6UXX9; 1 site.
DR PhosphoSitePlus; Q6UXX9; -.
DR BioMuta; RSPO2; -.
DR DMDM; 147744588; -.
DR MassIVE; Q6UXX9; -.
DR PaxDb; Q6UXX9; -.
DR PeptideAtlas; Q6UXX9; -.
DR PRIDE; Q6UXX9; -.
DR ProteomicsDB; 67672; -. [Q6UXX9-1]
DR ProteomicsDB; 67673; -. [Q6UXX9-2]
DR ProteomicsDB; 67674; -. [Q6UXX9-3]
DR Antibodypedia; 26506; 101 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 CTD; 340419; -.
DR DisGeNET; 340419; -.
DR GeneCards; RSPO2; -.
DR HGNC; HGNC:28583; RSPO2.
DR HPA; ENSG00000147655; Tissue enhanced (brain, 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; 1441603at2759; -.
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; 11 hits in 1068 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 107 other tissues.
DR ExpressionAtlas; Q6UXX9; baseline and differential.
DR Genevisible; Q6UXX9; HS.
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; -; 1.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR042993; RSPO2/4.
DR InterPro; IPR043601; Rspo_Fu-CRD_dom.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR PANTHER; PTHR46987:SF4; PTHR46987:SF4; 1.
DR Pfam; PF15913; Furin-like_2; 1.
DR SMART; SM00261; FU; 2.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS50092; TSP1; 1.
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 ZNRF3-
FT binding; decreased ability to amplify WNT3A signaling;
FT 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
