protein_function: Activator of the canonical Wnt signaling pathway byacting as a ligand for LGR4-6 receptors, which acts as a keyregulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 orLGR6), LGR4-6 associate with phosphorylated LRP6 and frizzledreceptors that are activated by extracellular Wnt receptors,triggering the canonical Wnt signaling pathway to increaseexpression of target genes. Also regulates the canonical Wnt,beta-catenin-dependent pathway and non-canonical Wnt signaling byacting as an inhibitor of ZNRF3, an important regulator of the Wntsignaling 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 ofangiogenesis by controlling vascular stability and pruning: actsby activating the non-canonical Wnt signaling pathway inendothelial cells (By similarity)..
R-spondin-3 is a protein that in humans is encoded by the RSPO3 gene. 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.