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Showing Protein R-spondin-1 (HMDBP14467)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP14467
Secondary Accession Numbers None
Name R-spondin-1
Synonyms
  1. Roof plate-specific spondin-1
  2. hRspo1
Gene Name RSPO1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors (PubMed:29769720). Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination. Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1 (PubMed:17804805).
Pathways
  • Wnt signaling pathway
Reactions Not Available
GO Classification
Biological Process
positive regulation of canonical Wnt receptor signaling pathway
positive regulation of protein phosphorylation
Wnt receptor signaling pathway
regulation of receptor internalization
positive regulation of Wnt receptor signaling pathway
Cellular Component
nucleus
extracellular region
Molecular Function
G protein-coupled receptor binding
receptor binding
heparin binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 263
Molecular Weight 28959.01
Theoretical pI 9.189
Pfam Domain Function
Signals
  • 1-20;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q2MKA7
UniProtKB/Swiss-Prot Entry Name RSPO1_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  4. Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K: Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science. 2005 Aug 19;309(5738):1256-9. doi: 10.1126/science.1112521. [PubMed:16109882 ]
  5. Parma P, Radi O, Vidal V, Chaboissier MC, Dellambra E, Valentini S, Guerra L, Schedl A, Camerino G: R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet. 2006 Nov;38(11):1304-9. doi: 10.1038/ng1907. Epub 2006 Oct 15. [PubMed:17041600 ]
  6. Binnerts ME, Kim KA, Bright JM, Patel SM, Tran K, Zhou M, Leung JM, Liu Y, Lomas WE 3rd, Dixon M, Hazell SA, Wagle M, Nie WS, Tomasevic N, Williams J, Zhan X, Levy MD, Funk WD, Abo A: R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14700-5. doi: 10.1073/pnas.0702305104. Epub 2007 Sep 5. [PubMed:17804805 ]
  7. Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, Boutros M, Cruciat CM, Niehrs C: LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and Wnt/PCP signalling. EMBO Rep. 2011 Sep 30;12(10):1055-61. doi: 10.1038/embor.2011.175. [PubMed:21909076 ]
  8. de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es JE, Guardavaccaro D, Schasfoort RB, Mohri Y, Nishimori K, Mohammed S, Heck AJ, Clevers H: Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature. 2011 Jul 4;476(7360):293-7. doi: 10.1038/nature10337. [PubMed:21727895 ]
  9. Gong X, Carmon KS, Lin Q, Thomas A, Yi J, Liu Q: LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. PLoS One. 2012;7(5):e37137. doi: 10.1371/journal.pone.0037137. Epub 2012 May 17. [PubMed:22615920 ]
  10. Szenker-Ravi E, Altunoglu U, Leushacke M, Bosso-Lefevre C, Khatoo M, Thi Tran H, Naert T, Noelanders R, Hajamohideen A, Beneteau C, de Sousa SB, Karaman B, Latypova X, Basaran S, Yucel EB, Tan TT, Vlaminck L, Nayak SS, Shukla A, Girisha KM, Le Caignec C, Soshnikova N, Uyguner ZO, Vleminckx K, Barker N, Kayserili H, Reversade B: RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6. Nature. 2018 May;557(7706):564-569. doi: 10.1038/s41586-018-0118-y. Epub 2018 May 16. [PubMed:29769720 ]
  11. Peng WC, de Lau W, Forneris F, Granneman JC, Huch M, Clevers H, Gros P: Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5. Cell Rep. 2013 Jun 27;3(6):1885-92. doi: 10.1016/j.celrep.2013.06.009. [PubMed:23809763 ]
  12. Wang D, Huang B, Zhang S, Yu X, Wu W, Wang X: Structural basis for R-spondin recognition by LGR4/5/6 receptors. Genes Dev. 2013 Jun 15;27(12):1339-44. doi: 10.1101/gad.219360.113. Epub 2013 Jun 11. [PubMed:23756652 ]
  13. Chen PH, Chen X, Lin Z, Fang D, He X: The structural basis of R-spondin recognition by LGR5 and RNF43. Genes Dev. 2013 Jun 15;27(12):1345-50. doi: 10.1101/gad.219915.113. Epub 2013 Jun 11. [PubMed:23756651 ]