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Identification
HMDB Protein ID HMDBP01659
Secondary Accession Numbers
  • 6989
Name Hereditary hemochromatosis protein
Synonyms
  1. HLA-H
Gene Name HFE
Protein Type Unknown
Biological Properties
General Function Involved in immune response
Specific Function Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin
Pathways Not Available
Reactions Not Available
GO Classification
Component
mhc protein complex
mhc class i protein complex
membrane
cell part
macromolecular complex
protein complex
Process
antigen processing and presentation
immune system process
immune response
Cellular Location
  1. Membrane
  2. Single-pass type I membrane protein
Gene Properties
Chromosome Location Chromosome:6
Locus 6p21.3
SNPs HFE
Gene Sequence
>1047 bp
ATGGGCCCGCGAGCCAGGCCGGCGCTTCTCCTCCTGATGCTTTTGCAGACCGCGGTCCTG
CAGGGGCGCTTGCTGCGTTCACACTCTCTGCACTACCTCTTCATGGGTGCCTCAGAGCAG
GACCTTGGTCTTTCCTTGTTTGAAGCTTTGGGCTACGTGGATGACCAGCTGTTCGTGTTC
TATGATCATGAGAGTCGCCGTGTGGAGCCCCGAACTCCATGGGTTTCCAGTAGAATTTCA
AGCCAGATGTGGCTGCAGCTGAGTCAGAGTCTGAAAGGGTGGGATCACATGTTCACTGTT
GACTTCTGGACTATTATGGAAAATCACAACCACAGCAAGGAGTCCCACACCCTGCAGGTC
ATCCTGGGCTGTGAAATGCAAGAAGACAACAGTACCGAGGGCTACTGGAAGTACGGGTAT
GATGGGCAGGACCACCTTGAATTCTGCCCTGACACACTGGATTGGAGAGCAGCAGAACCC
AGGGCCTGGCCCACCAAGCTGGAGTGGGAAAGGCACAAGATTCGGGCCAGGCAGAACAGG
GCCTACCTGGAGAGGGACTGCCCTGCACAGCTGCAGCAGTTGCTGGAGCTGGGGAGAGGT
GTTTTGGACCAACAAGTGCCTCCTTTGGTGAAGGTGACACATCATGTGACCTCTTCAGTG
ACCACTCTACGGTGTCGGGCCTTGAACTACTACCCCCAGAACATCACCATGAAGTGGCTG
AAGGATAAGCAGCCAATGGATGCCAAGGAGTTCGAACCTAAAGACGTATTGCCCAATGGG
GATGGGACCTACCAGGGCTGGATAACCTTGGCTGTACCCCCTGGGGAAGAGCAGAGATAT
ACGTGCCAGGTGGAGCACCCAGGCCTGGATCAGCCCCTCATTGTGATCTGGGAGCCCTCA
CCGTCTGGCACCCTAGTCATTGGAGTCATCAGTGGAATTGCTGTTTTTGTCGTCATCTTG
TTCATTGGAATTTTGTTCATAATATTAAGGAAGAGGCAGGGTTCAAGAGGAGCCATGGGG
CACTACGTCTTAGCTGAACGTGAGTGA
Protein Properties
Number of Residues 348
Molecular Weight 40107.7
Theoretical pI 6.57
Pfam Domain Function
Signals
  • 1-22
Transmembrane Regions
  • 307-330
Protein Sequence
>Hereditary hemochromatosis protein
MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVF
YDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQV
ILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNR
AYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWL
KDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWEPS
PSGTLVIGVISGIAVFVVILFIGILFIILRKRQGSRGAMGHYVLAERE
GenBank ID Protein 4504377
UniProtKB/Swiss-Prot ID Q30201
UniProtKB/Swiss-Prot Entry Name HFE_HUMAN
PDB IDs
GenBank Gene ID NM_000410.3
GeneCard ID HFE
GenAtlas ID HFE
HGNC ID HGNC:4886
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Brady JJ, Jackson HA, Roberts AG, Morgan RR, Whatley SD, Rowlands GL, Darby C, Shudell E, Watson R, Paiker J, Worwood MW, Elder GH: Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda. J Invest Dermatol. 2000 Nov;115(5):868-74. [PubMed:11069625 ]
  3. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258 ]
  4. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996 Aug;13(4):399-408. [PubMed:8696333 ]
  5. Ruddy DA, Kronmal GS, Lee VK, Mintier GA, Quintana L, Domingo R Jr, Meyer NC, Irrinki A, McClelland EE, Fullan A, Mapa FA, Moore T, Thomas W, Loeb DB, Harmon C, Tsuchihashi Z, Wolff RK, Schatzman RC, Feder JN: A 1.1-Mb transcript map of the hereditary hemochromatosis locus. Genome Res. 1997 May;7(5):441-56. [PubMed:9149941 ]
  6. Albig W, Drabent B, Burmester N, Bode C, Doenecke D: The haemochromatosis candidate gene HFE (HLA-H) of man and mouse is located in syntenic regions within the histone gene cluster. J Cell Biochem. 1998 May 1;69(2):117-26. [PubMed:9548560 ]
  7. Rhodes DA, Trowsdale J: Alternate splice variants of the hemochromatosis gene Hfe. Immunogenetics. 1999 Apr;49(4):357-9. [PubMed:10079302 ]
  8. Thenie A, Orhant M, Gicquel I, Fergelot P, Le Gall JY, David V, Mosser J: The HFE gene undergoes alternate splicing processes. Blood Cells Mol Dis. 2000 Apr;26(2):155-62. [PubMed:11001625 ]
  9. Feder JN, Penny DM, Irrinki A, Lee VK, Lebron JA, Watson N, Tsuchihashi Z, Sigal E, Bjorkman PJ, Schatzman RC: The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1472-7. [PubMed:9465039 ]
  10. Lebron JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, Mintier GA, Feder JN, Bjorkman PJ: Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell. 1998 Apr 3;93(1):111-23. [PubMed:9546397 ]
  11. Dupradeau F, Altenberg-Greulich B, Warin R, Fuentes V, Monti J, Rochette J: A 3-dimensional model building by homology of the HFE protein: molecular consequences and application to antibody development. Biochim Biophys Acta. 2000 Sep 29;1481(2):213-21. [PubMed:11018711 ]
  12. Bennett MJ, Lebron JA, Bjorkman PJ: Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature. 2000 Jan 6;403(6765):46-53. [PubMed:10638746 ]
  13. Carella M, D'Ambrosio L, Totaro A, Grifa A, Valentino MA, Piperno A, Girelli D, Roetto A, Franco B, Gasparini P, Camaschella C: Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. Am J Hum Genet. 1997 Apr;60(4):828-32. [PubMed:9106528 ]
  14. Roberts AG, Whatley SD, Morgan RR, Worwood M, Elder GH: Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic porphyria cutanea tarda. Lancet. 1997 Feb 1;349(9048):321-3. [PubMed:9024376 ]
  15. Sampietro M, Piperno A, Lupica L, Arosio C, Vergani A, Corbetta N, Malosio I, Mattioli M, Fracanzani AL, Cappellini MD, Fiorelli G, Fargion S: High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda. Hepatology. 1998 Jan;27(1):181-4. [PubMed:9425935 ]
  16. Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N, Obando J, Di Bisceglie A, Tattrie C, Tortorelli K, LeClair P, Mercurio MG, Lambrecht RW: Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America. Hepatology. 1998 Jun;27(6):1661-9. [PubMed:9620340 ]
  17. Mura C, Raguenes O, Ferec C: HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood. 1999 Apr 15;93(8):2502-5. [PubMed:10194428 ]
  18. Barton JC, Sawada-Hirai R, Rothenberg BE, Acton RT: Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. Blood Cells Mol Dis. 1999 Jun-Aug;25(3-4):147-55. [PubMed:10575540 ]
  19. de Villiers JN, Hillermann R, Loubser L, Kotze MJ: Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria. Hum Mol Genet. 1999 Aug;8(8):1517-22. [PubMed:10401000 ]
  20. Merryweather-Clarke AT, Simonsen H, Shearman JD, Pointon JJ, Norgaard-Pedersen B, Robson KJ: A retrospective anonymous pilot study in screening newborns for HFE mutations in Scandinavian populations. Hum Mutat. 1999;13(2):154-9. [PubMed:10094552 ]
  21. Bradbury R, Fagan E, Payne SJ: Two novel polymorphisms (E277K and V212V) in the haemochromatosis gene HFE. Hum Mutat. 2000 Jan;15(1):120. [PubMed:10612845 ]
  22. Moczulski DK, Grzeszczak W, Gawlik B: Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy. Diabetes Care. 2001 Jul;24(7):1187-91. [PubMed:11423500 ]
  23. Imanishi H, Liu W, Cheng J, Ikeda N, Amuro Y, Hada T: Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for HFE gene. Intern Med. 2001 Jun;40(6):479-83. [PubMed:11446670 ]
  24. Jones DC, Young NT, Pigott C, Fuggle SV, Barnardo MC, Marshall SE, Bunce M: Comprehensive hereditary hemochromatosis genotyping. Tissue Antigens. 2002 Dec;60(6):481-8. [PubMed:12542741 ]
  25. Le Gac G, Dupradeau FY, Mura C, Jacolot S, Scotet V, Esnault G, Mercier AY, Rochette J, Ferec C: Phenotypic expression of the C282Y/Q283P compound heterozygosity in HFE and molecular modeling of the Q283P mutation effect. Blood Cells Mol Dis. 2003 May-Jun;30(3):231-7. [PubMed:12737937 ]
  26. Biasiotto G, Belloli S, Ruggeri G, Zanella I, Gerardi G, Corrado M, Gobbi E, Albertini A, Arosio P: Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload. Clin Chem. 2003 Dec;49(12):1981-8. [PubMed:14633868 ]
  27. Wigg AJ, Harley H, Casey G: Heterozygous recipient and donor HFE mutations associated with a hereditary haemochromatosis phenotype after liver transplantation. Gut. 2003 Mar;52(3):433-5. [PubMed:12584229 ]
  28. Bento MC, Ribeiro ML, Relvas L: Gene symbol: HFE. Disease: Haemochromatosis. Hum Genet. 2004 Mar;114(4):405. [PubMed:15046077 ]
  29. Ka C, Le Gac G, Dupradeau FY, Rochette J, Ferec C: The Q283P amino-acid change in HFE leads to structural and functional consequences similar to those described for the mutated 282Y HFE protein. Hum Genet. 2005 Sep;117(5):467-75. Epub 2005 Jun 18. [PubMed:15965644 ]
  30. Dupradeau FY, Pissard S, Coulhon MP, Cadet E, Foulon K, Fourcade C, Goossens M, Case DA, Rochette J: An unusual case of hemochromatosis due to a new compound heterozygosity in HFE (p.[Gly43Asp;His63Asp]+[Cys282Tyr]): structural implications with respect to binding with transferrin receptor 1. Hum Mutat. 2008 Jan;29(1):206. [PubMed:18157833 ]