E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (PubMed:18313049, PubMed:22575959, PubMed:22895187). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with AKAP8L, NONO and SFPQ (PubMed:18313049, PubMed:18655028). Interacts with FZD5 (PubMed:22895187). Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:23756651). Interacts with RSPO2 (PubMed:29769720). Interacts with LMBR1L (By similarity). According to a report, may be secreted. Expressed in fetal kidney, fetal lung, in colon cancer tissues, hepatocellular carcinomas and lung adenocarcinomas. Overexpressed in colorectal cancer cell lines. Autoubiquitinated. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Acts as a cytotoxic T-lymphocyte tumor antigen, suggesting that it may be used as a target for cancer immunotherapy. Belongs to the ZNRF3 family. Truncated N-terminus.