WIF1

WNT inhibitory factor 1
Rendering of WIF domain of WIF-1 based on the NMR structure PDB ID 2D3J.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2D3J​, 2YGN​, 2YGO​, 2YGP​, 2YGQ​
Identifiers
Symbols	WIF1 ; WIF-1
External IDs	OMIM: 605186 MGI: 1344332 HomoloGene: 31430 GeneCards: WIF1 Gene
Gene ontology Molecular function • protein binding Cellular component • extracellular region Biological process • signal transduction • multicellular organismal development • Wnt signaling pathway • positive regulation of fat cell differentiation • negative regulation of canonical Wnt signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	11197	24117
Ensembl	ENSG00000156076	ENSMUSG00000020218
UniProt	Q9Y5W5	Q9WUA1
RefSeq (mRNA)	NM_007191	NM_011915
RefSeq (protein)	NP_009122	NP_036045
Location (UCSC)	Chr 12: 65.05 – 65.12 Mb	Chr 10: 121.03 – 121.1 Mb
PubMed search

Wnt inhibitory factor 1 is a protein that in humans is encoded by the WIF1 gene.^[1] WIF1 is a lipid-binding protein that binds to Wnt proteins and prevents them from triggering signalling.^[2][3][4]

Function

WNT proteins are extracellular signaling molecules involved in the control of embryonic development. This gene encodes a secreted protein, which binds WNT proteins and inhibits their activities. This protein contains a WNT inhibitory factor (WIF) domain and 5 epidermal growth factor (EGF)-like domains. It may be involved in mesoderm segmentation. This protein is found to be present in fish, amphibia and mammals.^[1]

References

1. "Entrez Gene: WIF1 WNT inhibitory factor 1".
2. Malinauskas T, Aricescu AR, Lu W, Siebold C, Jones EY (July 2011). "Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1". Nature Structural & Molecular Biology 18 (8): 886–893. doi:10.1038/nsmb.2081. PMC 3430870. PMID 21743455.
3. Malinauskas T (2008). "Docking of fatty acids into the WIF domain of the human Wnt inhibitory factor-1". Lipids 43 (3): 227–30. doi:10.1007/s11745-007-3144-3. PMID 18256869.
4. Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM, Samos CH, Nusse R, Dawid IB, Nathans J (Apr 1999). "A new secreted protein that binds to Wnt proteins and inhibits their activities". Nature 398 (6726): 431–6. doi:10.1038/18899. PMID 10201374.

Further reading

• Shepelev MV, Korobko EV, Korobko IV (2006). "[WIF1: perspectives of application in oncology]". Mol. Gen. Mikrobiol. Virusol. (4): 3–7. PMID 17094650.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Reguart N, He B, Xu Z, et al. (2004). "Cloning and characterization of the promoter of human Wnt inhibitory factor-1.". Biochem. Biophys. Res. Commun. 323 (1): 229–34. doi:10.1016/j.bbrc.2004.08.075. PMID 15351726.
• Esufali S, Bapat B (2004). "Cross-talk between Rac1 GTPase and dysregulated Wnt signaling pathway leads to cellular redistribution of beta-catenin and TCF/LEF-mediated transcriptional activation.". Oncogene 23 (50): 8260–71. doi:10.1038/sj.onc.1208007. PMID 15377999.
• Ohigashi T, Mizuno R, Nakashima J, et al. (2005). "Inhibition of Wnt signaling downregulates Akt activity and induces chemosensitivity in PTEN-mutated prostate cancer cells.". Prostate 62 (1): 61–8. doi:10.1002/pros.20117. PMID 15389810.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Simon M, Grandage VL, Linch DC, Khwaja A (2005). "Constitutive activation of the Wnt/beta-catenin signalling pathway in acute myeloid leukaemia.". Oncogene 24 (14): 2410–20. doi:10.1038/sj.onc.1208431. PMID 15735743.
• Taniguchi H, Yamamoto H, Hirata T, et al. (2005). "Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers.". Oncogene 24 (53): 7946–52. doi:10.1038/sj.onc.1208910. PMID 16007117.
• Lin YC, You L, Xu Z, et al. (2006). "Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines.". Biochem. Biophys. Res. Commun. 341 (2): 635–40. doi:10.1016/j.bbrc.2005.12.220. PMID 16427602.
• Urakami S, Shiina H, Enokida H, et al. (2006). "Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in bladder cancer through aberrant canonical Wnt/beta-catenin signaling pathway.". Clin. Cancer Res. 12 (2): 383–91. doi:10.1158/1078-0432.CCR-05-1344. PMID 16428476.
• Liepinsh E, Bányai L, Patthy L, Otting G (2006). "NMR structure of the WIF domain of the human Wnt-inhibitory factor-1.". J. Mol. Biol. 357 (3): 942–50. doi:10.1016/j.jmb.2006.01.047. PMID 16476441.
• Batra S, Shi Y, Kuchenbecker KM, et al. (2006). "Wnt inhibitory factor-1, a Wnt antagonist, is silenced by promoter hypermethylation in malignant pleural mesothelioma.". Biochem. Biophys. Res. Commun. 342 (4): 1228–32. doi:10.1016/j.bbrc.2006.02.084. PMID 16516163.
• Chim CS, Chan WW, Pang A, Kwong YL (2006). "Preferential methylation of Wnt inhibitory factor-1 in acute promyelocytic leukemia: an independent poor prognostic factor.". Leukemia 20 (5): 907–9. doi:10.1038/sj.leu.2404176. PMID 16525492.
• Urakami S, Shiina H, Enokida H, et al. (2006). "Combination analysis of hypermethylated Wnt-antagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection.". Clin. Cancer Res. 12 (7 Pt 1): 2109–16. doi:10.1158/1078-0432.CCR-05-2468. PMID 16609023.
• Milutinovic S, D'Alessio AC, Detich N, Szyf M (2007). "Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes.". Carcinogenesis 28 (3): 560–71. doi:10.1093/carcin/bgl167. PMID 17012225.
• Queimado L, Lopes CS, Reis AM (2007). "WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors.". Genes Chromosomes Cancer 46 (3): 215–25. doi:10.1002/gcc.20402. PMID 17171686.
• Chan SL, Cui Y, van Hasselt A, et al. (2007). "The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas.". Lab. Invest. 87 (7): 644–50. doi:10.1038/labinvest.3700547. PMID 17384664.
• Veeck J, Wild PJ, Fuchs T, et al. (2009). "Prognostic relevance of Wnt-inhibitory factor-1 (WIF1) and Dickkopf-3 (DKK3) promoter methylation in human breast cancer.". BMC Cancer 9: 1–13. doi:10.1186/1471-2407-9-217. PMC 2717119. PMID 19570204.