RNF43

RNF43
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4KNG
Identifiers
Aliases	RNF43 , RNF124, URCC, ring finger protein 43, SSPCS
External IDs	OMIM: 612482; MGI: 2442609; HomoloGene: 37742; GeneCards: RNF43; OMA:RNF43 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q22 Start 58,353,676 bp [1] End 58,417,595 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11|11 C Start 87,553,548 bp [2] End 87,626,365 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in rectum gingival epithelium mucosa of sigmoid colon mucosa of transverse colon duodenum parotid gland jejunal mucosa epithelium of colon right adrenal cortex gonad Top expressed in saccule thin ascending limb of loop of Henle ectoderm otic vesicle otic placode genital tubercle duodenum female urethra crypt of lieberkuhn of small intestine zygote More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion binding protein binding frizzled binding ubiquitin protein ligase activity ubiquitin-protein transferase activity transferase activity Cellular component integral component of membrane plasma membrane integral component of plasma membrane nuclear envelope endoplasmic reticulum membrane nucleus endoplasmic reticulum membrane Biological process negative regulation of Wnt signaling pathway Wnt signaling pathway Wnt receptor catabolic process protein ubiquitination stem cell proliferation ubiquitin-dependent protein catabolic process multicellular organism development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54894 207742 Ensembl ENSG00000108375 ENSMUSG00000034177 UniProt Q68DV7 Q5NCP0 RefSeq (mRNA) NM_001305544 NM_001305545 NM_017763 NM_172448 NM_001363437 RefSeq (protein) NP_001292473 NP_001292474 NP_060233 NP_766036 NP_001350366 Location (UCSC) Chr 17: 58.35 – 58.42 Mb Chr 11: 87.55 – 87.63 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ring finger protein 43 is a protein that in humans is encoded by the RNF43 gene. ^[5]

Function

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]

References

1. GRCh38: Ensembl release 89: ENSG00000108375 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034177 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Ring finger protein 43" . Retrieved 2018-02-21.
6. Li S, Zhang R, Lavrijsen M, van den Bosch TP, Peppelenbosch MP, Smits R (2023). "Issues with RNF43 antibodies to reliably detect intracellular location". PLOS ONE. 18 (4): e0283894. Bibcode:2023PLoSO..1883894L. doi: 10.1371/journal.pone.0283894 . PMC   10079101 . PMID   37023034.
7. Li S, Lavrijsen M, Bakker A, Magierowski M, Magierowska K, Liu P, Wang W, Peppelenbosch MP, Smits R (2020). "Commonly observed RNF43 mutations retain functionality in attenuating Wnt/β-catenin signaling and unlikely confer Wnt-dependency onto colorectal cancers". Oncogene. 39 (17): 3458–3472. doi:10.1038/s41388-020-1232-5. PMID   32103169.

Further reading

• 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. PMID   15492824.
• 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. PMID   18313049.
• Shinada K, Tsukiyama T, Sho T, Okumura F, Asaka M, Hatakeyama S (January 2011). "RNF43 interacts with NEDL1 and regulates p53-mediated transcription" (PDF). Biochem. Biophys. Res. Commun. 404 (1): 143–7. doi:10.1016/j.bbrc.2010.11.082. hdl: 2115/44929 . PMID   21108931.
• 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. PMID   22895187. S2CID   4386072.
• Ryland GL, Hunter SM, Doyle MA, Rowley SM, Christie M, Allan PE, Bowtell DD, Gorringe KL, Campbell IG (February 2013). "RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary". J. Pathol. 229 (3): 469–76. doi: 10.1002/path.4134 . PMID   23096461. S2CID   24919944.
• Xing C, Zhou W, Ding S, Xie H, Zhang W, Yang Z, Wei B, Chen K, Su R, Cheng J, Zheng S, Zhou L (January 2013). "Reversing effect of ring finger protein 43 inhibition on malignant phenotypes of human hepatocellular carcinoma". Mol. Cancer Ther. 12 (1): 94–103. doi: 10.1158/1535-7163.MCT-12-0672 . PMID   23136185.
• Jiang X, Hao HX, Growney JD, Woolfenden S, Bottiglio C, Ng N, Lu B, Hsieh MH, Bagdasarian L, Meyer R, Smith TR, Avello M, Charlat O, Xie Y, Porter JA, Pan S, Liu J, McLaughlin ME, Cong F (July 2013). "Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma". Proc. Natl. Acad. Sci. U.S.A. 110 (31): 12649–54. Bibcode:2013PNAS..11012649J. doi: 10.1073/pnas.1307218110 . PMC   3732970 . PMID   23847203.
• 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. PMID   24001777.
• Zebisch M, Xu Y, Krastev C, MacDonald BT, Chen M, Gilbert RJ, He X, Jones EY (2013). "Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin". Nat Commun. 4: 2787. Bibcode:2013NatCo...4.2787Z. doi:10.1038/ncomms3787. PMC   3905715 . PMID   24225776.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.