Human hemochromatosis protein also known as the HFE protein is a protein which in humans is encoded by the HFE gene. The HFE gene is located on short arm of chromosome 6 at location 6p21.3. Unusually, the official gene symbol (HFE for High Iron Fe) is not an abbreviation of the official name (hemochromatosis).[1]
Function
The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta-2 microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. [2]
Clinical significance
The iron storage disorder, hereditary haemochromatosis,(HHC) is an autosomal recessive genetic disorder that usually results from defects in this gene.
The mutation or polymorphism most commonly associated with hemochromatosis is p.C282Y. About 1/200 of people of Northern European origin have two copies of this variant, they, particularly males are at high risk of developing hemochromatosis [3].
Interactions
The HFE protein has been shown to interact with TFRC.[4][5] Its primary mode of action is then through regulation of the iron storage hormone hepcidin.[6]
References
- ^ "HGNC: HFE". http://www.genenames.org/data/hgnc_data.php?hgnc_id=4886.
- ^ "Entrez Gene: HFE hemochromatosis". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3077.
- ^ "Hemochromatosis". http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm.
- ^ Feder, J N; Penny D M, Irrinki A, Lee V K, Lebrón J A, Watson N, Tsuchihashi Z, Sigal E, Bjorkman P J, Schatzman R C (Feb. 1998). "The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (4): 1472–7. ISSN 0027-8424. PMID 9465039.
- ^ West, A P; Bennett M J, Sellers V M, Andrews N C, Enns C A, Bjorkman P J (Dec. 2000). "Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE". J. Biol. Chem. (UNITED STATES) 275 (49): 38135–8. doi:10.1074/jbc.C000664200. ISSN 0021-9258. PMID 11027676.
- ^ "Regulation of Iron Metabolism by Hepcidin". http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.nutr.26.061505.111303.
Further reading
- Dorak MT, Burnett AK, Worwood M (2003). "Hemochromatosis gene in leukemia and lymphoma.". Leuk. Lymphoma 43 (3): 467–77. doi:10.1080/10428190290011930. PMID 12002748.
- Beutler E (2003). "The HFE Cys282Tyr mutation as a necessary but not sufficient cause of clinical hereditary hemochromatosis.". Blood 101 (9): 3347–50. doi:10.1182/blood-2002-06-1747. PMID 12707220.
- Ombiga J, Adams LA, Tang K, et al. (2006). "Screening for HFE and iron overload.". Semin. Liver Dis. 25 (4): 402–10. doi:10.1055/s-2005-923312. PMID 16315134.
- Distante S (2006). "Genetic predisposition to iron overload: prevalence and phenotypic expression of hemochromatosis-associated HFE-C282Y gene mutation.". Scand. J. Clin. Lab. Invest. 66 (2): 83–100. doi:10.1080/00365510500495616. PMID 16537242.
- Zamboni P, Gemmati D (2007). "Clinical implications of gene polymorphisms in venous leg ulcer: a model in tissue injury and reparative process.". Thromb. Haemost. 98 (1): 131–7. PMID 17598005.
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1a6z: HFE (HUMAN) HEMOCHROMATOSIS PROTEIN
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1de4: HEMOCHROMATOSIS PROTEIN HFE COMPLEXED WITH TRANSFERRIN RECEPTOR
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External links
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