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Reviewed, UniProtKB/Swiss-Prot Q30201 (HFE_HUMAN)

Last modified November 3, 2009. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Hereditary hemochromatosis protein
Alternative name(s):
    HLA-H
Gene names
Name: HFE
Synonyms: HLAH
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length348 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. Ref.9

Subunit structure

Binds TFR through the extracellular domain in a pH-dependent manner.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

In all tissues tested except brain.

Involvement in disease

Defects in HFE are a cause of hereditary hemochromatosis (HH) [MIM:235200]. HH is an autosomal recessive inborn disorder of iron metabolism. It is the most common recessive disease in Caucasians. HH is characterized by abnormal intestinal iron absorption and progressive increase of total body iron, which results in midlife in clinical complications including cirrhosis, cardiopathy, diabetes, endocrine dysfunctions, arthropathy, and susceptibility to liver cancer. Since the disease complications can be effectively prevented by regular phlebotomies, early diagnosis is most important to provide a normal life expectancy to the affected subjects. Ref.1 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33

Defects in HFE are a cause of porphyria variegata (PV) [MIM:176200]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. PV is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease. Ref.20

Defects in HFE are associated with susceptibility to diabetic nephropathy [MIM:612635]; also called susceptibility to microvascular complications of diabetes type 7 (MVCD7) or susceptibility to diabetic proliferative retinopathy. Diabetic nephropathy is a kidney disease and resultant kidney function impairment due to the long standing effects of diabetes on the microvasculature (glomerulus) of the kidney. Features include increased urine protein and declining kidney function.

Sequence similarities

Belongs to the MHC class I family.

Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Biological processImmune response
Ion transport
Iron transport
Transport
   Cellular componentMHC I
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainSignal
Transmembrane
   LigandIron
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processantigen processing and presentation of peptide antigen via MHC class I

Inferred from electronic annotation. Source: UniProtKB-KW

cellular iron ion homeostasis Ref.12

Traceable author statement. Source: ProtInc

immune response

Inferred from electronic annotation. Source: UniProtKB-KW

iron ion transport

Traceable author statement. Source: ProtInc

protein complex assembly Ref.12

Traceable author statement. Source: ProtInc

receptor-mediated endocytosis

Traceable author statement. Source: ProtInc

   Cellular componentMHC class I protein complex

Inferred from electronic annotation. Source: UniProtKB-KW

apical part of cell

Inferred from direct assay. Source: UniProtKB

basal part of cell

Inferred from direct assay. Source: UniProtKB

cytoplasmic vesicle

Inferred from direct assay. Source: UniProtKB

early endosome

Inferred from direct assay. Source: UniProtKB

integral to plasma membrane Ref.12

Traceable author statement. Source: ProtInc

perinuclear region of cytoplasm

Inferred from direct assay. Source: UniProtKB

recycling endosome

Inferred from direct assay. Source: UniProtKB

   Molecular functioniron ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 10 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q30201-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 2 (identifier: Q30201-2)

Also known as: delE2;

The sequence of this isoform differs from the canonical sequence as follows:
     26-114: RSHSLHYLFM...IMENHNHSKE → Q
Isoform 3 (identifier: Q30201-3)

Also known as: del14E4;

The sequence of this isoform differs from the canonical sequence as follows:
     207-220: Missing.
Isoform 4 (identifier: Q30201-4)

Also known as: delE214E4;

The sequence of this isoform differs from the canonical sequence as follows:
     26-114: RSHSLHYLFM...IMENHNHSKE → Q
     207-220: Missing.
Isoform 5 (identifier: Q30201-5)

The sequence of this isoform differs from the canonical sequence as follows:
     26-49: RSHSLHYLFMGASEQDLGLSLFEA → P
Isoform 6 (identifier: Q30201-6)

The sequence of this isoform differs from the canonical sequence as follows:
     27-206: Missing.
Isoform 7 (identifier: Q30201-7)

Also known as: delE3;

The sequence of this isoform differs from the canonical sequence as follows:
     114-205: Missing.
Isoform 8 (identifier: Q30201-8)

Also known as: 1043-2283del,intron6ins;

The sequence of this isoform differs from the canonical sequence as follows:
     275-276: GE → KY
     277-348: Missing.
Isoform 9 (identifier: Q30201-9)

Also known as: delE3-7;

The sequence of this isoform differs from the canonical sequence as follows:
     144-161: DHLEFCPDTLDWRAAEPR → VLQDTIYSSEVSSLGIKF
     162-348: Missing.
Isoform 10 (identifier: Q30201-10)

Also known as: 562-878del;

The sequence of this isoform differs from the canonical sequence as follows:
     114-219: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222
Chain23 – 348326Hereditary hemochromatosis protein
PRO_0000018892

Regions

Topological domain23 – 306284Extracellular Potential
Transmembrane307 – 33024 Potential
Topological domain331 – 34818Cytoplasmic Potential
Domain207 – 29892Ig-like C1-type
Region23 – 11492Alpha-1
Region115 – 20591Alpha-2
Region206 – 29792Alpha-3
Region298 – 3069Connecting peptide

Amino acid modifications

Glycosylation1101N-linked (GlcNAc...) Potential
Glycosylation1301N-linked (GlcNAc...) Potential
Glycosylation2341N-linked (GlcNAc...) Potential
Disulfide bond124 ↔ 187
Disulfide bond225 ↔ 282

Natural variations

Alternative sequence26 – 11489RSHSL…NHSKE → Q in isoform 2 and isoform 4.
VSP_003218
Alternative sequence26 – 4924RSHSL…SLFEA → P in isoform 5.
VSP_003219
Alternative sequence27 – 206180Missing in isoform 6.
VSP_003220
Alternative sequence114 – 219106Missing in isoform 10.
VSP_003222
Alternative sequence114 – 20592Missing in isoform 7.
VSP_003221
Alternative sequence144 – 16118DHLEF…AAEPR → VLQDTIYSSEVSSLGIKF in isoform 9.
VSP_003223
Alternative sequence162 – 348187Missing in isoform 9.
VSP_003224
Alternative sequence207 – 22014Missing in isoform 3 and isoform 4.
VSP_003225
Alternative sequence275 – 2762GE → KY in isoform 8.
VSP_003226
Alternative sequence277 – 34872Missing in isoform 8.
VSP_003227
Natural variant61R → S in HH. Ref.30
VAR_042506
Natural variant431G → D in HH; located on the same allele as D-63. Ref.33
VAR_042507
Natural variant531V → M
VAR_008111
Natural variant591V → M
VAR_008112
Natural variant631H → D in HH and PV; increased frequency of the Asp-63 allele among patients with diabetic nephropathy. dbSNP rs1799945. Ref.1 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.25 Ref.27 Ref.29 Ref.33 Ref.24
VAR_004396
Natural variant651S → C in HH; mild form. dbSNP rs1800730. Ref.18 Ref.19 Ref.22 Ref.27 Ref.29
VAR_004397
Natural variant661R → C in HH. Ref.29
VAR_042508
Natural variant931G → R in HH. dbSNP rs28934597. Ref.19
VAR_008729
Natural variant1051I → T in HH. dbSNP rs28934596. Ref.19
VAR_008730
Natural variant1271Q → H in HH and PV. dbSNP rs28934595. Ref.20
VAR_008113
Natural variant1761A → V in HH; uncertain pathological significance. Ref.26
VAR_042509
Natural variant2171T → I: dbSNP rs4986950.
VAR_020270
Natural variant2241R → G in HH. Ref.29
VAR_042510
Natural variant2771E → K Rare polymorphism. Ref.23
VAR_008731
Natural variant2821C → Y in HH; the frequency of the Tyr-282 mutation is higher in patients with type 2 diabetes than it is in the general population of healthy subjects. dbSNP rs1800562. Ref.1 Ref.14 Ref.15 Ref.17 Ref.18 Ref.21 Ref.25 Ref.27 Ref.29 Ref.33 Ref.24
VAR_004398
Natural variant2831Q → P in HH; destabilizing effect on the tertiary structure of the protein; prevents the normal interaction between HFE and B2M and between HFE and TFRC; decreases the capacity of HFE to reduce transferrin-mediated iron uptake. Ref.28 Ref.32
VAR_037304
Natural variant2951V → A in HH. Ref.27 Ref.31
VAR_042511
Natural variant3301R → M in HH. Ref.20
VAR_008114

Experimental info

Sequence conflict261R → L in CAC80805. Ref.6
Sequence conflict2301Y → H in AAG29342. Ref.7
Sequence conflict2481A → T in AAG29575. Ref.7
Sequence conflict2561V → A in AAG29577. Ref.7
Sequence conflict2751G → E in AAG29342. Ref.7
Sequence conflict3111S → R in AAG29342. Ref.7
Sequence conflict3391M → V in AAG29577. Ref.7

Secondary structure

.................................................... 348
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 432EB9A314A55BEA

FASTA34840,108
        10         20         30         40         50         60 
MGPRARPALL LLMLLQTAVL QGRLLRSHSL HYLFMGASEQ DLGLSLFEAL GYVDDQLFVF 

        70         80         90        100        110        120 
YDHESRRVEP RTPWVSSRIS SQMWLQLSQS LKGWDHMFTV DFWTIMENHN HSKESHTLQV 

       130        140        150        160        170        180 
ILGCEMQEDN STEGYWKYGY DGQDHLEFCP DTLDWRAAEP RAWPTKLEWE RHKIRARQNR 

       190        200        210        220        230        240 
AYLERDCPAQ LQQLLELGRG VLDQQVPPLV KVTHHVTSSV TTLRCRALNY YPQNITMKWL 

       250        260        270        280        290        300 
KDKQPMDAKE FEPKDVLPNG DGTYQGWITL AVPPGEEQRY TCQVEHPGLD QPLIVIWEPS 

       310        320        330        340 
PSGTLVIGVI SGIAVFVVIL FIGILFIILR KRQGSRGAMG HYVLAERE 

« Hide

Isoform 2 (delE2).

Checksum: C30AC94F06A81AAA
Show »

FASTA26029,633
Isoform 3 (del14E4).

Checksum: 811D9D68BB9D7F3A
Show »

FASTA33438,625
Isoform 4 (delE214E4).

Checksum: 47B79FE7B8B49A0A
Show »

FASTA24628,151
Isoform 5.

Checksum: 626343ACFAA862EF
Show »

FASTA32537,514
Isoform 6.

Checksum: ABEBD094D95FFEA8
Show »

FASTA16818,777
Isoform 7 (delE3).

Checksum: 0E810B1BBACDF0BF
Show »

FASTA25629,194
Isoform 8 (1043-2283del,intron6ins).

Checksum: 3E0D2762D7476B82
Show »

FASTA27632,243
Isoform 9 (delE3-7).

Checksum: 5E288C5835DC3784
Show »

FASTA16118,651
Isoform 10 (562-878del).

Checksum: E423FF903128DB74
Show »

FASTA24227,711

References

« Hide 'large scale' references
[1]"A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis."
Feder J.N., Gnirke A., Thomas W., Tsuchihashi Z., Ruddy D.A., Basava A., Dormishian F., Domingo R. Jr., Ellis M.C. Jr., Fullan A., Hinton L.M., Jones N.L., Kimmel B.E., Kronmal G.S., Lauer P., Lee V.K., Loeb D.B., Mapa F.A. expand/collapse author list , McClelland E., Meyer N.C., Mintier G.A., Moeller N., Moore T., Morikang E., Prass C.E., Quintana L., Starnes S.M., Schatzman R.C., Brunke K.J., Drayna D.T., Risch N.J., Bacon B.R., Wolff R.K.
Nat. Genet. 13:399-409(1996) [PubMed: 8696333] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS HH ASP-63 AND TYR-282.
[2]"A 1.1-Mb transcript map of the hereditary hemochromatosis locus."
Ruddy D.A., Kronmal G.S., Lee V.K., Mintier G.A., Quintana L., Domingo R. Jr., Meyer N.C., Irrinki A., McClelland E.E., Fullan A., Mapa F.A., Moore T., Thomas W., Loeb D.B., Harmon C., Tsuchihashi Z., Wolff R.K., Schatzman R.C., Feder J.N.
Genome Res. 7:441-456(1997) [PubMed: 9149941] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[3]"The haemochromatosis candidate gene HFE (HLA-H) of man and mouse is located in syntenic regions within the histone gene."
Albig W., Drabent B., Burmester N., Bode C., Doenecke D.
J. Cell. Biochem. 69:117-126(1998) [PubMed: 9548560] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]"Hereditary hemochromatosis genomic structure and organization of HLA-H gene."
Gasparini P.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]"Alternate splice variants of the hemochromatosis gene Hfe."
Rhodes D.A., Trowsdale J.
Immunogenetics 49:357-359(1999) [PubMed: 10079302] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
[6]"Identification of different alternative splicing forms of the HFE gene."
Oliva R., Sanchez M.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 5; 6 AND 7).
[7]"The HFE gene undergoes alternate splicing processes."
Thenie A., Orhant M., Gicquel I., Fergelot P., Le Gall J.-Y., David V., Mosser J.
Blood Cells Mol. Dis. 26:155-162(2000) [PubMed: 11001625] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 7; 8; 9 AND 10).
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[9]"The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding."
Feder J.N., Penny D.M., Irrinki A., Lee V.K., Lebron J.A., Watson N., Tsuchihashi Z., Sigal E., Bjorkman P.J., Schatzman R.C.
Proc. Natl. Acad. Sci. U.S.A. 95:1472-1477(1998) [PubMed: 9465039] [Abstract]
Cited for: FUNCTION.
[10]"Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor."
Lebron J.A., Bennett M.J., Vaughn D.E., Chirino A.J., Snow P.M., Mintier G.A., Feder J.N., Bjorkman P.J.
Cell 93:111-123(1998) [PubMed: 9546397] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 23-297 IN COMPLEX WITH TFR.
[11]"A 3-dimensional model building by homology of the HFE protein: molecular consequences and application to antibody development."
Dupradeau F., Altenberg-Greulich B., Warin R., Fuentes V., Monti J., Rochette J.
Biochim. Biophys. Acta 1481:213-221(2000) [PubMed: 11018711] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 26-293 IN COMPLEX WITH B2MG.
[12]"Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor."
Bennett M.J., Lebron J.A., Bjorkman P.J.
Nature 403:46-53(2000) [PubMed: 10638746] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-297 IN COMPLEX WITH TFR.
[13]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[14]"Mutation analysis of the HLA-H gene in Italian hemochromatosis patients."
Carella M., D'Ambrosio L., Totaro A., Grifa A., Valentino M.A., Piperno A., Girelli D., Roetto A., Franco B., Gasparini P., Camaschella C.
Am. J. Hum. Genet. 60:828-832(1997) [PubMed: 9106528] [Abstract]
Cited for: VARIANTS HH ASP-63 AND TYR-282.
[15]"Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic porphyria cutanea tarda."
Roberts A.G., Whatley S.D., Morgan R.R., Worwood M., Elder G.H.
Lancet 349:321-323(1997) [PubMed: 9024376] [Abstract]
Cited for: VARIANT HH/PCT TYR-282.
[16]"High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda."
Sampietro M., Piperno A., Lupica L., Arosio C., Vergani A., Corbetta N., Malosio I., Mattioli M., Fracanzani A.L., Cappellini M.D., Fiorelli G., Fargion S.
Hepatology 27:181-184(1998) [PubMed: 9425935] [Abstract]
Cited for: VARIANT HH/PCT ASP-63.
[17]"Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America."
Bonkovsky H.L., Poh-Fitzpatrick M., Pimstone N., Obando J., Di Bisceglie A., Tattrie C., Tortorelli K., LeClair P., Mercurio M.G., Lambrecht R.W.
Hepatology 27:1661-1669(1998) [PubMed: 9620340] [Abstract]
Cited for: VARIANTS HH/PCT ASP-63 AND TYR-282.
[18]"HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis."
Mura C., Raguenes O., Ferec C.
Blood 93:2502-2505(1999) [PubMed: 10194428] [Abstract]
Cited for: VARIANTS HH ASP-63; CYS-65 AND TYR-282.
[19]"Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands."
Barton J.C., Sawada-Hirai R., Rothenberg B.E., Acton R.T.
Blood Cells Mol. Dis. 25:147-155(1999) [PubMed: 10575540] [Abstract]
Cited for: VARIANTS HH CYS-65; ARG-93 AND THR-105.
[20]"Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria."
de Villiers J.N.P., Hillermann R., Loubser L., Kotze M.J.
Hum. Mol. Genet. 8:1517-1522(1999) [PubMed: 10401000] [Abstract]
Cited for: VARIANTS PV ASP-63 AND HIS-127, VARIANT HH MET-330, VARIANTS MET-53 AND MET-59.
[21]"A retrospective anonymous pilot study in screening newborns for HFE mutations in Scandinavian populations."
Merryweather-Clarke A.T., Simonsen H., Shearman J.D., Pointon J.J., Norgaard-Pedersen B., Robson K.J.H.
Hum. Mutat. 13:154-159(1999) [PubMed: 10094552] [Abstract]
Cited for: VARIANTS HH ASP-63 AND TYR-282.
[22]"A novel missense mutation S65C in the HFE gene with a possible role in hereditary haemochromatosis."
Fagan E., Payne S.J.
Hum. Mutat. 13:507-508(1999)
Cited for: VARIANT HH CYS-65.
[23]"Two novel polymorphisms (E277K and V212V) in the haemochromatosis gene HFE."
Bradbury R., Fagan E., Payne S.J.
Hum. Mutat. 15:120-120(2000) [PubMed: 10612845] [Abstract]
Cited for: VARIANT LYS-277.
[24]"Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda."
Brady J.J., Jackson H.A., Roberts A.G., Morgan R.R., Whatley S.D., Rowlands G.L., Darby C., Shudell E., Watson R., Paiker J., Worwood M.W., Elder G.H.
J. Invest. Dermatol. 115:868-874(2000) [PubMed: 11069625] [Abstract]
Cited for: VARIANTS ASP-63 AND TYR-282.
[25]"Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy."
Moczulski D.K., Grzeszczak W., Gawlik B.
Diabetes Care 24:1187-1191(2001) [PubMed: 11423500] [Abstract]
Cited for: VARIANTS HH ASP-63 AND TYR-282, ASSOCIATION WITH DIABETIC NEPHROPATHY SUSCEPTIBILITY.
[26]"Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for HFE gene."
Imanishi H., Liu W., Cheng J., Ikeda N., Amuro Y., Hada T.
Intern. Med. 40:479-483(2001) [PubMed: 11446670] [Abstract]
Cited for: VARIANT HH VAL-176.
[27]"Comprehensive hereditary hemochromatosis genotyping."
Jones D.C., Young N.T., Pigott C., Fuggle S.V., Barnardo M.C.N.M., Marshall S.E., Bunce M.
Tissue Antigens 60:481-488(2002) [PubMed: 12542741] [Abstract]
Cited for: VARIANTS HH ASP-63; CYS-65; TYR-282 AND ALA-295.
[28]"Phenotypic expression of the C282Y/Q283P compound heterozygosity in HFE and molecular modeling of the Q283P mutation effect."
Le Gac G., Dupradeau F.-Y., Mura C., Jacolot S., Scotet V., Esnault G., Mercier A.-Y., Rochette J., Ferec C.
Blood Cells Mol. Dis. 30:231-237(2003) [PubMed: 12737937] [Abstract]
Cited for: VARIANT HH PRO-283, CHARACTERIZATION OF VARIANT HH PRO-283.
[29]"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."
Biasiotto G., Belloli S., Ruggeri G., Zanella I., Gerardi G., Corrado M., Gobbi E., Albertini A., Arosio P.
Clin. Chem. 49:1981-1988(2003) [PubMed: 14633868] [Abstract]
Cited for: VARIANTS HH ASP-63; CYS-65; CYS-66; GLY-224 AND TYR-282.
[30]"Heterozygous recipient and donor HFE mutations associated with a hereditary haemochromatosis phenotype after liver transplantation."
Wigg A.J., Harley H., Casey G.
Gut 52:433-435(2003) [PubMed: 12584229] [Abstract]
Cited for: VARIANT HH SER-6.
[31]"Gene symbol: HFE. Disease: haemochromatosis."
Bento M.C., Ribeiro M.L., Relvas L.
Hum. Genet. 114:405-405(2004) [PubMed: 15046077] [Abstract]
Cited for: VARIANT HH ALA-295.
[32]"The Q283P amino-acid change in HFE leads to structural and functional consequences similar to those described for the mutated 282Y HFE protein."
Ka C., Le Gac G., Dupradeau F.-Y., Rochette J., Ferec C.
Hum. Genet. 117:467-475(2005) [PubMed: 15965644] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT HH PRO-283.
[33]"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."
Dupradeau F.-Y., Pissard S., Coulhon M.-P., Cadet E., Foulon K., Fourcade C., Goossens M., Case D.A., Rochette J.
Hum. Mutat. 29:206-206(2008) [PubMed: 18157833] [Abstract]
Cited for: VARIANTS HH ASP-43; ASP-63 AND TYR-282.
+Additional computationally mapped references.

Cross-references

Sequence databases

U60319 mRNA. Translation: AAC51823.1.
U91328 Genomic DNA. Translation: AAB82083.1.
Z92910 Genomic DNA. Translation: CAB07442.1.
Y09801 expand/collapse EMBL AC list , Y09800, Y09803, Y09799 Genomic DNA. Translation: CAA70934.1.
AF079407 mRNA. Translation: AAC62646.1.
AF079408 mRNA. Translation: AAC62647.1.
AF079409 mRNA. Translation: AAC62648.1.
AJ249335 mRNA. Translation: CAC67792.1.
AJ249336 mRNA. Translation: CAC67793.1.
AJ249337 mRNA. Translation: CAC67794.1.
AJ250635 mRNA. Translation: CAC80805.1.
AF115264 mRNA. Translation: AAG29571.1.
AF115265 mRNA. Translation: AAG29572.1.
AF144240 mRNA. Translation: AAG29575.1.
AF144242 mRNA. Translation: AAG29577.1.
AF149804 mRNA. Translation: AAG29342.1.
BC117201 mRNA. Translation: AAI17202.1.
BC117203 mRNA. Translation: AAI17204.1.
IPIIPI00029419.
IPI00215955.
IPI00218211.
IPI00218212.
IPI00218213.
IPI00218215.
IPI00218218.
IPI00218221.
IPI00294375.
RefSeqNP_000401.1.
NP_620572.1.
NP_620573.1.
NP_620575.1.
NP_620576.1.
NP_620577.1.
NP_620578.1.
NP_620579.1.
UniGeneHs.233325

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1A6ZX-ray2.60A/C23-297[»]
1C42model-A26-293[»]
1DE4X-ray2.80A/D/G23-297[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:2737N.
STRINGQ30201.

Proteomic databases

PRIDEQ30201.

Genome annotation databases

EnsemblENST00000309234; ENSP00000311698; ENSG00000010704; Homo sapiens. [Genome view]
ENST00000317896; ENSP00000313776; ENSG00000010704; Homo sapiens. [Genome view]
ENST00000336625; ENSP00000337819; ENSG00000010704; Homo sapiens. [Genome view]
ENST00000349999; ENSP00000259699; ENSG00000010704; Homo sapiens. [Genome view]
ENST00000352392; ENSP00000315936; ENSG00000010704; Homo sapiens. [Genome view]
ENST00000353147; ENSP00000312342; ENSG00000010704; Homo sapiens. [Genome view]
ENST00000397022; ENSP00000380217; ENSG00000010704; Homo sapiens. [Genome view]
GeneID3077.
KEGGhsa:3077.
UCSCuc003nfx.1. human.
uc003nfz.1. human.
uc003nga.1. human.
uc003ngb.1. human.
uc003ngc.1. human.
uc003ngd.1. human.

Organism-specific databases

CTD3077.
GeneCardsGC06P026195.
H-InvDBHIX0025100.
HIX0032768.
HGNCHGNC:4886. HFE.
HPAHPA017276.
MIM176200. phenotype.
235200. gene+phenotype.
612635. phenotype.
Orphanet445. Hemochromatosis.
139498. Hemochromatosis, adult form.
79230. Hemochromatosis, juvenile form.
738. Porphyria.
79473. Porphyria, Variegata.
PharmGKBPA29263.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ30201.
OMACQALNFY.

Gene expression databases

ArrayExpressQ30201.
BgeeQ30201.
GenevestigatorQ30201.
GermOnlineENSG00000010704. Homo sapiens.

Family and domain databases

InterProIPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR011161. MHC_I-like_Ag-recog.
IPR001039. MHC_I_a_a1/a2.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:3.30.500.10. MHC_I-like_Ag-recog. 1 hit.
PfamPF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
[Graphical view]
PRINTSPR01638. MHCCLASSI.
SMARTSM00407. IGc1. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio12169.
SOURCESearch...

Entry information

Entry nameHFE_HUMAN
AccessionPrimary (citable) accession number: Q30201
Secondary accession number(s): O75929 expand/collapse secondary AC list , O75930, O75931, Q17RT0, Q96KU5, Q96KU7, Q96KU8, Q9HC64, Q9HC68, Q9HC70, Q9HC83
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 3, 2009
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents