R-Spondin-3 (RSPO3) Human Active Protein

This gene belongs to the R-spondin family. The encoded protein plays a role in the regulation of Wnt (wingless-type MMTV integration site family)/beta-catenin and Wnt/planar cell polarity (PCP) signaling pathways, which are involved in development, cell growth and disease pathogenesis. Genome-wide association studies suggest a correlation of this gene with bone mineral density and risk of fracture. This gene may be involved in tumor development. [provided by RefSeq, Jul 2013]

Function: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. 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. Ref.7 Ref.8 Ref.9

Subunit structure: Interacts with the extracellular domain of FZD8 and LRP6. It however does not form a ternary complex with FZD8 and LRP6. Interacts with WNT1. Binds heparin

By similarity. Interacts with LGR4, LGR5 and LGR6. Ref.7 Ref.8 Ref.9

Subcellular location: Secreted

By similarity.

Tissue specificity: Ubiquitously expressed. Expressed at higher level in placenta, small intestine, fetal thymus and lymph node. Ref.1

Domain: The FU repeats are required for activation and stabilization of beta-catenin

By similarity.

Miscellaneous: Upon injection into mice, it induces rapid onset of crypt cell proliferation involving beta-catenin stabilization. It also displays efficacy in a model of chemotherapy-induced intestinal mucositis (Ref.6).

Sequence similarities: Belongs to the R-spondin family.Contains 2 FU (furin-like) repeats.Contains 1 TSP type-1 domain.