RSPO1_HUMAN
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 03-AUG-2022, entry version 140.
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 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 [13]
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 [14]
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 [15]
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; 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:0000250|UniProtKB:Q9Z132}. Nucleus
CC {ECO:0000250|UniProtKB:Q9Z132}. Note=Seems to mainly localize to
CC nucleoli. {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 -!- 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="http://atlasgeneticsoncology.org/Genes/RSPO1ID44137ch1p34.html";
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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; 13.
DR MINT; Q2MKA7; -.
DR STRING; 9606.ENSP00000348944; -.
DR GlyGen; Q2MKA7; 1 site.
DR iPTMnet; Q2MKA7; -.
DR PhosphoSitePlus; Q2MKA7; -.
DR BioMuta; RSPO1; -.
DR DMDM; 97189599; -.
DR MassIVE; Q2MKA7; -.
DR PaxDb; Q2MKA7; -.
DR PeptideAtlas; Q2MKA7; -.
DR PRIDE; Q2MKA7; -.
DR ProteomicsDB; 61396; -. [Q2MKA7-1]
DR ProteomicsDB; 61397; -. [Q2MKA7-2]
DR ProteomicsDB; 61398; -. [Q2MKA7-3]
DR Antibodypedia; 31749; 285 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 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; CREGLYL; -.
DR OrthoDB; 1441603at2759; -.
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; 10 hits in 1073 CRISPR screens.
DR ChiTaRS; RSPO1; human.
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 87 other tissues.
DR Genevisible; Q2MKA7; HS.
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 Gene3D; 2.20.100.10; -; 1.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR042991; RSPO1.
DR InterPro; IPR043601; Rspo_Fu-CRD_dom.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR PANTHER; PTHR46987:SF5; PTHR46987:SF5; 1.
DR Pfam; PF15913; Furin-like_2; 1.
DR Pfam; PF00090; TSP_1; 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 3D-structure; Alternative splicing; Disulfide bond; Glycoprotein;
KW Heparin-binding; Nucleus; Palmoplantar keratoderma; Reference proteome;
KW Repeat; Secreted; 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:0000255"
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 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
