The protein encoded by this gene is a RING-type E3 ubiquitin ligase and is predicted to contain a transmembrane domain, a protease-associated domain, an ectodomain, and a cytoplasmic RING domain. This protein is thought to negatively regulate Wnt signaling, and expression of this gene results in an increase in ubiquitination of frizzled receptors, an alteration in their subcellular distribution, resulting in reduced surface levels of these receptors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]. A nuclear function for the protein has also been proposed but recently it was shown that this is an artifact, nuclear staining being an artifact of the antibodies employed.[6] Cancer-associated RNF43 mutations lead to activation of β-catenin signaling through aberrantly increasing Wnt-receptor levels at the membrane. Importantly, inactivating N-terminal RNF43 mutations render cancer cells sensitive to Wnt antagonists, but mutations elsewhere do not.[7]
Yagyu R, Furukawa Y, Lin YM, Shimokawa T, Yamamura T, Nakamura Y (November 2004). "A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer". Int. J. Oncol. 25 (5): 1343–8. PMID15492824.
Sugiura T, Yamaguchi A, Miyamoto K (April 2008). "A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95". Exp. Cell Res. 314 (7): 1519–28. doi:10.1016/j.yexcr.2008.01.013. PMID18313049.
Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJ, Maurice MM, Clevers H (August 2012). "Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors". Nature. 488 (7413): 665–9. Bibcode:2012Natur.488..665K. doi:10.1038/nature11308. PMID22895187. S2CID4386072.
Zou Y, Wang F, Liu FY, Huang MZ, Li W, Yuan XQ, Huang OP, He M (November 2013). "RNF43 mutations are recurrent in Chinese patients with mucinous ovarian carcinoma but absent in other subtypes of ovarian cancer". Gene. 531 (1): 112–6. doi:10.1016/j.gene.2013.08.054. PMID24001777.
