ID RSPO1_HUMAN Reviewed; 263 AA. AC Q2MKA7; A2A420; Q0H8S6; Q14C72; Q5T0F2; Q8N7L5; DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 07-FEB-2006, sequence version 1. DT 27-NOV-2024, entry version 153. DE RecName: Full=R-spondin-1; DE AltName: Full=Roof plate-specific spondin-1; DE Short=hRspo1; DE Flags: Precursor; GN Name=RSPO1; 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), AND FUNCTION. RX PubMed=16109882; DOI=10.1126/science.1112521; RA Kim K.-A., Kakitani M., Zhao J., Oshima T., Tang T., Binnerts M., Liu Y., RA Boyle B., Park E., Emtage P., Funk W.D., Tomizuka K.; RT "Mitogenic influence of human R-spondin1 on the intestinal epithelium."; RL Science 309:1256-1259(2005). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, AND RP INVOLVEMENT IN PALMOPLANTAR HYPERKERATOSIS WITH SQUAMOUS CELL CARCINOMA OF RP SKIN AND SEX REVERSAL. RX PubMed=17041600; DOI=10.1038/ng1907; RA Parma P., Radi O., Vidal V., Chaboissier M.C., Dellambra E., Valentini S., RA Guerra L., Schedl A., Camerino G.; RT "R-spondin1 is essential in sex determination, skin differentiation and RT malignancy."; RL Nat. Genet. 38:1304-1309(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Uterus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 KREM1. RX PubMed=17804805; DOI=10.1073/pnas.0702305104; RA Binnerts M.E., Kim K.A., Bright J.M., Patel S.M., Tran K., Zhou M., RA Leung J.M., Liu Y., Lomas W.E. III, Dixon M., Hazell S.A., Wagle M., RA Nie W.S., Tomasevic N., Williams J., Zhan X., Levy M.D., Funk W.D., Abo A.; RT "R-Spondin1 regulates Wnt signaling by inhibiting internalization of RT LRP6."; RL Proc. Natl. Acad. Sci. U.S.A. 104:14700-14705(2007). RN [7] RP FUNCTION, AND INTERACTION WITH ZNRF3. RX PubMed=22575959; DOI=10.1038/nature11019; RA Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H., RA Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T., RA Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F.; RT "ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner."; RL Nature 485:195-200(2012). RN [8] 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 [9] 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 [10] 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 [11] RP FUNCTION, AND INTERACTION WITH LGR4 AND LGR5. 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 [12] RP GLYCOSYLATION AT ASN-137, AND MUTAGENESIS OF ASN-137. RX PubMed=27123103; DOI=10.3892/ol.2016.4425; RA Tsuchiya M., Niwa Y., Simizu S.; RT "N-glycosylation of R-spondin1 at Asn137 negatively regulates its secretion RT and Wnt/beta-catenin signaling-enhancing activity."; RL Oncol. Lett. 11:3279-3286(2016). RN [13] RP GLYCOSYLATION AT TRP-153 AND TRP-156, SUBCELLULAR LOCATION, MUTAGENESIS OF RP TRP-153 AND TRP-156, AND MASS SPECTROMETRY. RX PubMed=26764097; DOI=10.1091/mbc.e15-06-0373; RA Niwa Y., Suzuki T., Dohmae N., Simizu S.; RT "Identification of DPY19L3 as the C-mannosyltransferase of R-spondin1 in RT human cells."; RL Mol. Biol. Cell 27:744-756(2016). RN [14] RP FUNCTION. 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 (2.0 ANGSTROMS) OF 31-146 IN COMPLEX WITH LGR5, RP FUNCTION, INTERACTION WITH LGR5, MUTAGENESIS OF ARG-66; ARG-70; GLN-71; RP GLY-73; ARG-87; PHE-106 AND PHE-110, 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 39-128 IN COMPLEX WITH LGR4, RP FUNCTION, SUBUNIT, MUTAGENESIS OF ARG-87; PHE-106; PHE-110; LYS-122 AND RP ARG-124, 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 [17] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 35-144 IN COMPLEX WITH LGR5 AND RP RNF43, SUBUNIT, AND DISULFIDE BONDS. 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: Activator of the canonical Wnt signaling pathway by acting as CC a ligand for LGR4-6 receptors (PubMed:29769720). Upon binding to LGR4-6 CC (LGR4, LGR5 or LGR6), LGR4-6 associate 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. Also regulates the canonical Wnt/beta-catenin- CC dependent pathway and non-canonical Wnt signaling by acting as an CC inhibitor of ZNRF3, an important regulator of the Wnt signaling CC pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively CC regulate the TGF-beta pathway. Has a essential roles in ovary CC determination. Regulates Wnt signaling by antagonizing DKK1/KREM1- CC mediated internalization of LRP6 through an interaction with KREM1 CC (PubMed:17804805). {ECO:0000269|PubMed:16109882, CC ECO:0000269|PubMed:17804805, ECO:0000269|PubMed:21727895, CC ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22575959, CC ECO:0000269|PubMed:22615920, ECO:0000269|PubMed:22815884, CC ECO:0000269|PubMed:23756652, ECO:0000269|PubMed:23809763, CC ECO:0000269|PubMed:29769720}. CC -!- SUBUNIT: Interacts with the extracellular domain of FZD8 and LRP6. It CC however does not form a ternary complex with FZD8 and LRP6. Interacts CC with WNT1. Binds heparin (By similarity). Interacts with ZNRF3; CC promoting indirect interaction between ZNRF3 and LGR4 and membrane CC clearance of ZNRF3. Interacts with LGR4, LGR5 and LGR6. Identified in a CC complex composed of RNF43, LGR5 and RSPO1. Interacts (via FU repeats) CC with KREM1 (PubMed:17804805). {ECO:0000250|UniProtKB:Q9Z132, CC ECO:0000269|PubMed:17804805, ECO:0000269|PubMed:21727895, CC ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22575959, CC ECO:0000269|PubMed:22615920, ECO:0000269|PubMed:22815884, CC ECO:0000269|PubMed:23756651, ECO:0000269|PubMed:23756652, CC ECO:0000269|PubMed:23809763}. CC -!- INTERACTION: CC Q2MKA7; P21964-2: COMT; NbExp=3; IntAct=EBI-10045219, EBI-10200977; CC Q2MKA7; O75473: LGR5; NbExp=3; IntAct=EBI-10045219, EBI-4402067; CC Q2MKA7; Q9ULT6: ZNRF3; NbExp=6; IntAct=EBI-10045219, EBI-949772; CC Q2MKA7; B0BLW3: lgr4; Xeno; NbExp=2; IntAct=EBI-10045219, EBI-7425077; CC Q2MKA7; Q5SSZ7: Znrf3; Xeno; NbExp=3; IntAct=EBI-10045219, EBI-21993315; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26764097, CC ECO:0000269|PubMed:27123103}. Nucleus {ECO:0000250|UniProtKB:Q9Z132}. CC Note=Seems to mainly localize to nucleoli. CC {ECO:0000250|UniProtKB:Q9Z132}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q2MKA7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q2MKA7-2; Sequence=VSP_018320; CC Name=3; CC IsoId=Q2MKA7-3; Sequence=VSP_043265; CC -!- TISSUE SPECIFICITY: Abundantly expressed in adrenal glands, ovary, CC testis, thyroid and trachea but not in bone marrow, spinal cord, CC stomach, leukocytes colon, small intestine, prostate, thymus and CC spleen. {ECO:0000269|PubMed:17041600}. CC -!- DOMAIN: The FU repeats are required for activation and stabilization of CC beta-catenin. {ECO:0000250}. CC -!- PTM: C-, and N-glycosylated. N-glycosylation at Asn-137, negatively CC influences its secretion and enhancing effect on Wnt/beta-catenin CC signaling (PubMed:27123103). C-mannosylation at Trp-156 by DPY19L3 is CC required for its secretion and regulates the enhancing activity of Wnt CC signaling (PubMed:26764097). {ECO:0000269|PubMed:26764097, CC ECO:0000269|PubMed:27123103}. CC -!- DISEASE: Keratoderma, palmoplantar, with squamous cell carcinoma of CC skin and sex reversal (PKKSCC) [MIM:610644]: A recessive syndrome CC characterized by XX (female to male) SRY-independent sex reversal, CC palmoplantar hyperkeratosis and predisposition to squamous cell CC carcinoma of the skin. {ECO:0000269|PubMed:17041600}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Upon injection into mice, it induces rapid onset of CC crypt cell proliferation involving beta-catenin stabilization. It also CC displays efficacy in a model of chemotherapy-induced intestinal CC mucositis suggesting possible therapeutic application in CC gastrointestinal diseases. CC -!- SIMILARITY: Belongs to the R-spondin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44137/RSPO1"; 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; DQ318235; ABC54570.1; -; mRNA. DR EMBL; DQ165084; ABA54597.1; -; mRNA. DR EMBL; DQ165085; ABA54598.1; -; mRNA. DR EMBL; AK098225; BAC05263.1; -; mRNA. DR EMBL; AL513220; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC114966; AAI14967.1; -; mRNA. DR CCDS; CCDS41304.1; -. [Q2MKA7-1] DR CCDS; CCDS55590.1; -. [Q2MKA7-3] DR CCDS; CCDS55591.1; -. [Q2MKA7-2] DR RefSeq; NP_001033722.1; NM_001038633.3. [Q2MKA7-1] DR RefSeq; NP_001229837.1; NM_001242908.1. [Q2MKA7-1] DR RefSeq; NP_001229838.1; NM_001242909.1. [Q2MKA7-2] DR RefSeq; NP_001229839.1; NM_001242910.1. [Q2MKA7-3] DR RefSeq; XP_006710646.1; XM_006710583.3. [Q2MKA7-1] DR PDB; 4BSO; X-ray; 2.20 A; A=31-146. DR PDB; 4BSP; X-ray; 2.00 A; A=31-146. DR PDB; 4BSR; X-ray; 3.20 A; C/D=31-146. DR PDB; 4BSS; X-ray; 3.20 A; C/D/G/H=31-146. DR PDB; 4BST; X-ray; 4.30 A; C/D=31-146. DR PDB; 4BSU; X-ray; 3.20 A; C/D/G/H=31-146. DR PDB; 4CDK; X-ray; 2.80 A; E/F/G/H=31-145. DR PDB; 4KNG; X-ray; 2.50 A; M/P=35-144. DR PDB; 4KT1; X-ray; 2.50 A; E=39-128. DR PDB; 4LI2; X-ray; 3.19 A; B=33-144. DR PDB; 4QXF; X-ray; 2.25 A; C/E=34-135. DR PDBsum; 4BSO; -. DR PDBsum; 4BSP; -. DR PDBsum; 4BSR; -. DR PDBsum; 4BSS; -. DR PDBsum; 4BST; -. DR PDBsum; 4BSU; -. DR PDBsum; 4CDK; -. DR PDBsum; 4KNG; -. DR PDBsum; 4KT1; -. DR PDBsum; 4LI2; -. DR PDBsum; 4QXF; -. DR AlphaFoldDB; Q2MKA7; -. DR SMR; Q2MKA7; -. DR BioGRID; 129926; 15. DR CORUM; Q2MKA7; -. DR DIP; DIP-59895N; -. DR IntAct; Q2MKA7; 14. DR MINT; Q2MKA7; -. DR STRING; 9606.ENSP00000348944; -. DR GlyCosmos; Q2MKA7; 1 site, No reported glycans. DR GlyGen; Q2MKA7; 3 sites. DR iPTMnet; Q2MKA7; -. DR PhosphoSitePlus; Q2MKA7; -. DR BioMuta; RSPO1; -. DR DMDM; 97189599; -. DR MassIVE; Q2MKA7; -. DR PaxDb; 9606-ENSP00000348944; -. DR PeptideAtlas; Q2MKA7; -. DR ProteomicsDB; 61396; -. [Q2MKA7-1] DR ProteomicsDB; 61398; -. [Q2MKA7-3] DR Antibodypedia; 31749; 297 antibodies from 33 providers. DR DNASU; 284654; -. DR Ensembl; ENST00000356545.7; ENSP00000348944.2; ENSG00000169218.14. [Q2MKA7-1] DR Ensembl; ENST00000401068.1; ENSP00000383846.1; ENSG00000169218.14. [Q2MKA7-1] DR Ensembl; ENST00000612451.4; ENSP00000479832.1; ENSG00000169218.14. [Q2MKA7-3] DR Ensembl; ENST00000615459.4; ENSP00000481178.1; ENSG00000169218.14. [Q2MKA7-2] DR GeneID; 284654; -. DR KEGG; hsa:284654; -. DR MANE-Select; ENST00000356545.7; ENSP00000348944.2; NM_001242908.2; NP_001229837.1. DR UCSC; uc031txm.2; human. [Q2MKA7-1] DR AGR; HGNC:21679; -. DR CTD; 284654; -. DR DisGeNET; 284654; -. DR GeneCards; RSPO1; -. DR HGNC; HGNC:21679; RSPO1. DR HPA; ENSG00000169218; Tissue enhanced (cervix, endometrium). DR MalaCards; RSPO1; -. DR MIM; 609595; gene. DR MIM; 610644; phenotype. DR neXtProt; NX_Q2MKA7; -. DR OpenTargets; ENSG00000169218; -. DR Orphanet; 85112; Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome. DR PharmGKB; PA142670967; -. DR VEuPathDB; HostDB:ENSG00000169218; -. DR eggNOG; KOG3525; Eukaryota. DR GeneTree; ENSGT00940000158871; -. DR HOGENOM; CLU_064219_0_1_1; -. DR InParanoid; Q2MKA7; -. DR OMA; ENCADCF; -. DR OrthoDB; 196918at2759; -. DR PhylomeDB; Q2MKA7; -. DR TreeFam; TF331799; -. DR PathwayCommons; Q2MKA7; -. DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination. DR SignaLink; Q2MKA7; -. DR SIGNOR; Q2MKA7; -. DR BioGRID-ORCS; 284654; 11 hits in 1149 CRISPR screens. DR ChiTaRS; RSPO1; human. DR EvolutionaryTrace; Q2MKA7; -. DR GeneWiki; RSPO1; -. DR GenomeRNAi; 284654; -. DR Pharos; Q2MKA7; Tbio. DR PRO; PR:Q2MKA7; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q2MKA7; protein. DR Bgee; ENSG00000169218; Expressed in endocervix and 88 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0002090; P:regulation of receptor internalization; IDA:BHF-UCL. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd00064; FU; 1. DR FunFam; 2.20.100.10:FF:000056; R-spondin 1; 1. DR FunFam; 2.10.220.10:FF:000003; R-spondin 3; 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; IPR051514; R-spondin. 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:SF5; R-SPONDIN-1; 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. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disulfide bond; Glycoprotein; KW Heparin-binding; Nucleus; Palmoplantar keratoderma; KW Proteomics identification; Reference proteome; Repeat; Secreted; KW Sensory transduction; Signal; Wnt signaling pathway. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..263 FT /note="R-spondin-1" FT /id="PRO_0000234436" FT REPEAT 34..85 FT /note="FU 1" FT REPEAT 91..135 FT /note="FU 2" FT DOMAIN 147..207 FT /note="TSP type-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT REGION 206..263 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 206..240 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 241..257 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 137 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:27123103" FT CARBOHYD 153 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000269|PubMed:26764097" FT CARBOHYD 156 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000269|PubMed:26764097" FT DISULFID 40..47 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 44..53 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 56..75 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 79..94 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 97..105 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 102..111 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 114..125 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 129..142 FT /evidence="ECO:0000269|PubMed:23809763, FT ECO:0007744|PDB:4BSO, ECO:0007744|PDB:4BSP, FT ECO:0007744|PDB:4BSR, ECO:0007744|PDB:4BSS, FT ECO:0007744|PDB:4BST, ECO:0007744|PDB:4BSU" FT DISULFID 148..190 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 159..166 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DISULFID 199..206 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT VAR_SEQ 1..32 FT /note="MRLGLCVVALVLSWTHLTISSRGIKGKRQRRI -> MIFRV (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_018320" FT VAR_SEQ 146..208 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17041600" FT /id="VSP_043265" FT MUTAGEN 66 FT /note="R->A: Strongly reduces activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23809763" FT MUTAGEN 66 FT /note="R->W: Reduces activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23809763" FT MUTAGEN 70 FT /note="R->C,E: Strongly reduces activation of Wnt FT signaling." FT /evidence="ECO:0000269|PubMed:23809763" FT MUTAGEN 71 FT /note="Q->E: No effect on activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23809763" FT MUTAGEN 71 FT /note="Q->R: Strongly reduces activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23809763" FT MUTAGEN 73 FT /note="G->E,R: Strongly reduces activation of Wnt FT signaling." FT /evidence="ECO:0000269|PubMed:23809763" FT MUTAGEN 87 FT /note="R->A: Nearly abolishes activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23756652, FT ECO:0000269|PubMed:23809763" FT MUTAGEN 106 FT /note="F->A: Abolishes activation of Wnt signaling. FT Abolishes LGR4 binding." FT /evidence="ECO:0000269|PubMed:23756652, FT ECO:0000269|PubMed:23809763" FT MUTAGEN 106 FT /note="F->E: Abolishes activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23756652, FT ECO:0000269|PubMed:23809763" FT MUTAGEN 110 FT /note="F->A: Nearly abolishes activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23756652, FT ECO:0000269|PubMed:23809763" FT MUTAGEN 110 FT /note="F->E: Abolishes activation of Wnt signaling." FT /evidence="ECO:0000269|PubMed:23756652, FT ECO:0000269|PubMed:23809763" FT MUTAGEN 122 FT /note="K->A: Strongly reduces affinity for LGR4." FT /evidence="ECO:0000269|PubMed:23756652" FT MUTAGEN 124 FT /note="R->A: Strongly reduces affinity for LGR4." FT /evidence="ECO:0000269|PubMed:23756652" FT MUTAGEN 137 FT /note="N->Q: Secretion of RSPO1 is decreased. Increased FT Wnt/beta-catenin signaling-enhancing effects." FT /evidence="ECO:0000269|PubMed:27123103" FT MUTAGEN 153 FT /note="W->A: Secretion of RSPO1 is decreased; when FT associated with A-156. Decreases activation of Wnt FT signaling; when associated with A-156." FT /evidence="ECO:0000269|PubMed:26764097" FT MUTAGEN 156 FT /note="W->A: Secretion of RSPO1 is decreased; when FT associated with A-153. Decreases activation of Wnt FT signaling; when associated with A-153." FT /evidence="ECO:0000269|PubMed:26764097" FT CONFLICT 150 FT /note="M -> V (in Ref. 3; BAC05263)" FT /evidence="ECO:0000305" FT STRAND 44..48 FT /evidence="ECO:0007829|PDB:4BSP" FT TURN 49..51 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 52..56 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 60..67 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 70..78 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 83..87 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 92..96 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 102..107 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 110..114 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:4BSP" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:4BSP" FT TURN 131..134 FT /evidence="ECO:0007829|PDB:4BSS" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:4LI2" SQ SEQUENCE 263 AA; 28959 MW; 43794A881B1C0278 CRC64; MRLGLCVVAL VLSWTHLTIS SRGIKGKRQR RISAEGSQAC AKGCELCSEV NGCLKCSPKL FILLERNDIR QVGVCLPSCP PGYFDARNPD MNKCIKCKIE HCEACFSHNF CTKCKEGLYL HKGRCYPACP EGSSAANGTM ECSSPAQCEM SEWSPWGPCS KKQQLCGFRR GSEERTRRVL HAPVGDHAAC SDTKETRRCT VRRVPCPEGQ KRRKGGQGRR ENANRNLARK ESKEAGAGSR RRKGQQQQQQ QGTVGPLTSA GPA //