R-spondin-1
Domain
The FU repeats are required for activation and stabilization of beta-catenin.
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).
Involvement in disease
Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal
PKKSCC
A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
C-, and N-glycosylated. N-glycosylation at Asn-137, negatively influences its secretion and enhancing effect on Wnt/beta-catenin signaling (PubMed:27123103). C-mannosylation at Trp-156 by DPY19L3 is required for its secretion and regulates the enhancing activity of Wnt signaling (PubMed:26764097).
Sequence Similarities
Belongs to the R-spondin family.
Tissue Specificity
Abundantly expressed in adrenal glands, ovary, testis, thyroid and trachea but not in bone marrow, spinal cord, stomach, leukocytes colon, small intestine, prostate, thymus and spleen.
Cellular localization
- Secreted
- Nucleus
- Seems to mainly localize to nucleoli.
Alternative names
R-spondin-1, Roof plate-specific spondin-1, hRspo1, RSPO1