Hmdb loader
Identification
HMDB Protein ID HMDBP14503
Secondary Accession Numbers None
Name R-spondin-3
Synonyms
  1. Protein with TSP type-1 repeat
  2. Roof plate-specific spondin-3
  3. Thrombospondin type-1 domain-containing protein 2
  4. hPWTSR
  5. hRspo3
Gene Name RSPO3
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, which acts as a key regulator of angiogenesis. 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 (PubMed:21727895, PubMed:21909076, PubMed:22615920). Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (By similarity) (PubMed:21727895, PubMed:21909076, PubMed:22615920). Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3 (PubMed:29769720).
Pathways
  • Wnt signaling pathway
Reactions Not Available
GO Classification
Biological Process
positive regulation of canonical Wnt receptor signaling pathway
sprouting angiogenesis
Wnt receptor signaling pathway
regulation of Wnt receptor signaling pathway
positive regulation of non-canonical Wnt signaling pathway
positive regulation of Wnt signaling pathway, planar cell polarity pathway
blood vessel remodeling
branching involved in labyrinthine layer morphogenesis
positive regulation of Wnt receptor signaling pathway
Cellular Component
extracellular region
Molecular Function
receptor binding
frizzled 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 272
Molecular Weight 30928.485
Theoretical pI 9.381
Pfam Domain Function
Signals
  • 1-21;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9BXY4
UniProtKB/Swiss-Prot Entry Name RSPO3_HUMAN
PDB IDs Not Available
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. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. Chen JZ, Wang S, Tang R, Yang QS, Zhao E, Chao Y, Ying K, Xie Y, Mao YM: Cloning and identification of a cDNA that encodes a novel human protein with thrombospondin type I repeat domain, hPWTSR. Mol Biol Rep. 2002 Sep;29(3):287-92. doi: 10.1023/a:1020479301379. [PubMed:12463421 ]
  9. Scholz B, Korn C, Wojtarowicz J, Mogler C, Augustin I, Boutros M, Niehrs C, Augustin HG: Endothelial RSPO3 Controls Vascular Stability and Pruning through Non-canonical WNT/Ca(2+)/NFAT Signaling. Dev Cell. 2016 Jan 11;36(1):79-93. doi: 10.1016/j.devcel.2015.12.015. [PubMed:26766444 ]