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Q30201 (HFE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hereditary hemochromatosis protein
Alternative name(s):
HLA-H
Gene names
Name:HFE
Synonyms:HLAH
OrganismHomo sapiens (Human) [Reference 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.11

Subunit structure

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

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed in all tissues tested except brain.

Polymorphism

Genetic variations in HFE define the transferrin serum level quantitative trait locus 2 (TFQTL2) [MIM:614193]. Iron is essential for biochemical functions such as oxygen transport and oxidative phosphorylation. Excessive iron can cause iron-overload-related liver diseases, whereas iron deficiency can lead to anemia. Iron status can be assessed by measuring the levels of serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin.

Involvement in disease

Hemochromatosis 1 (HFE1) [MIM:235200]: A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36

Variegate porphyria (VP) [MIM:176200]: A form of porphyria. 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. Variegate porphyria 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Iron overload due to HFE variants is a precipitating or exacerbating factor in variegate porphyria.

Microvascular complications of diabetes 7 (MVCD7) [MIM:612635]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Sequence similarities

Belongs to the MHC class I family.

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

Ontologies

Keywords
   Biological processImmunity
Ion transport
Iron transport
Transport
   Cellular componentMembrane
MHC I
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   LigandIron
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation

Inferred from Biological aspect of Ancestor. Source: RefGenome

antigen processing and presentation of peptide antigen via MHC class I

Inferred from electronic annotation. Source: UniProtKB-KW

cellular iron ion homeostasis

Traceable author statement Ref.15. Source: ProtInc

cellular response to iron ion starvation

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

hormone biosynthetic process

Inferred from electronic annotation. Source: Ensembl

immune response

Inferred from electronic annotation. Source: InterPro

iron ion import into cell

Inferred from direct assay PubMed 10085150. Source: UniProtKB

multicellular organismal iron ion homeostasis

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell mediated cytotoxicity

Inferred from electronic annotation. Source: InterPro

protein complex assembly

Traceable author statement Ref.15. Source: ProtInc

   Cellular_componentMHC class I protein complex

Inferred from electronic annotation. Source: UniProtKB-KW

apical part of cell

Inferred from direct assay PubMed 15880641. Source: UniProtKB

basal part of cell

Inferred from direct assay PubMed 15880641. Source: UniProtKB

cytoplasmic vesicle

Inferred from direct assay PubMed 15880641. Source: UniProtKB

early endosome

Inferred from direct assay PubMed 15880641. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.15. Source: ProtInc

perinuclear region of cytoplasm

Inferred from direct assay PubMed 15880641. Source: UniProtKB

plasma membrane

Traceable author statement Ref.15. Source: ProtInc

recycling endosome

Inferred from direct assay PubMed 15880641. Source: UniProtKB

   Molecular_functionantigen binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

peptide antigen binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 15880641. Source: UniProtKB

receptor binding

Inferred from physical interaction Ref.15. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

B2MP617693EBI-1028850,EBI-714718

Alternative products

This entry describes 11 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:
     26-26: R → L
     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.
Isoform 11 (identifier: Q30201-11)

The sequence of this isoform differs from the canonical sequence as follows:
     26-26: R → Q
     27-298: Missing.
Note: No experimental confirmation available.

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 – 33024Helical; 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 sequence261R → Q in isoform 11.
VSP_043477
Alternative sequence261R → L in isoform 6.
VSP_047336
Alternative sequence27 – 298272Missing in isoform 11.
VSP_043478
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 HFE1. Ref.33
VAR_042506
Natural variant431G → D in HFE1; associated with D-63 in one patient. Ref.36
VAR_042507
Natural variant531V → M. Ref.8 Ref.23
Corresponds to variant rs28934889 [ dbSNP | Ensembl ].
VAR_008111
Natural variant591V → M. Ref.23
Corresponds to variant rs28934890 [ dbSNP | Ensembl ].
VAR_008112
Natural variant631H → D Polymorphism associated with hemochromatosis and variegate porphyria; increased frequency among patients with diabetic nephropathy. Ref.1 Ref.8 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.27 Ref.28 Ref.36
Corresponds to variant rs1799945 [ dbSNP | Ensembl ].
VAR_004396
Natural variant651S → C in HFE1; mild form. Ref.21 Ref.22 Ref.25 Ref.30 Ref.32
Corresponds to variant rs1800730 [ dbSNP | Ensembl ].
VAR_004397
Natural variant661R → C in HFE1. Ref.32
VAR_042508
Natural variant931G → R in HFE1. Ref.22
Corresponds to variant rs28934597 [ dbSNP | Ensembl ].
VAR_008729
Natural variant1051I → T in HFE1. Ref.22
Corresponds to variant rs28934596 [ dbSNP | Ensembl ].
VAR_008730
Natural variant1271Q → H in HFE1. Ref.23
Corresponds to variant rs28934595 [ dbSNP | Ensembl ].
VAR_008113
Natural variant1761A → V in HFE1; uncertain pathological significance. Ref.29
VAR_042509
Natural variant2171T → I.
Corresponds to variant rs4986950 [ dbSNP | Ensembl ].
VAR_020270
Natural variant2241R → G in HFE1. Ref.32
VAR_042510
Natural variant2241R → Q. Ref.8
Corresponds to variant rs62625346 [ dbSNP | Ensembl ].
VAR_062279
Natural variant2771E → K Rare polymorphism. Ref.26
Corresponds to variant rs140080192 [ dbSNP | Ensembl ].
VAR_008731
Natural variant2821C → Y in HFE1; associated with susceptibility to porphyria cutanea tarda; associated with increased serum transferrin levels; higher frequency in patients with type 2 diabetes than in controls. Ref.1 Ref.8 Ref.17 Ref.18 Ref.20 Ref.21 Ref.24 Ref.27 Ref.28 Ref.30 Ref.32 Ref.36
Corresponds to variant rs1800562 [ dbSNP | Ensembl ].
VAR_004398
Natural variant2831Q → P in HFE1; 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.31 Ref.35
VAR_037304
Natural variant2951V → A in HFE1. Ref.30 Ref.34
Corresponds to variant rs143175221 [ dbSNP | Ensembl ].
VAR_042511
Natural variant3301R → M in HFE1. Ref.23
VAR_008114

Experimental info

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) [UniParc].

Checksum: C30AC94F06A81AAA
Show »

FASTA26029,633
Isoform 3 (del14E4) [UniParc].

Checksum: 811D9D68BB9D7F3A
Show »

FASTA33438,625
Isoform 4 (delE214E4) [UniParc].

Checksum: 47B79FE7B8B49A0A
Show »

FASTA24628,151
Isoform 5 [UniParc].

Checksum: 626343ACFAA862EF
Show »

FASTA32537,514
Isoform 6 [UniParc].

Checksum: 525C7094CEE850F9
Show »

FASTA16818,734
Isoform 7 (delE3) [UniParc].

Checksum: 0E810B1BBACDF0BF
Show »

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

Checksum: 3E0D2762D7476B82
Show »

FASTA27632,243
Isoform 9 (delE3-7) [UniParc].

Checksum: 5E288C5835DC3784
Show »

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

Checksum: E423FF903128DB74
Show »

FASTA24227,711
Isoform 11 [UniParc].

Checksum: B56810C036B9BEE9
Show »

FASTA768,208

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT HFE1 TYR-282, VARIANT ASP-63.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 7; 8; 9 AND 10).
[7]"Complete characterization of the 3' region of the human and mouse hereditary hemochromatosis HFE gene and detection of novel splicing forms."
Sanchez M., Bruguera M., Rodos J., Oliva R.
Blood Cells Mol. Dis. 27:35-43(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 5; 6; 7 AND 11).
[8]NIEHS SNPs program
Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-53; ASP-63; GLN-224 AND TYR-282.
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[11]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels."
Benyamin B., McRae A.F., Zhu G., Gordon S., Henders A.K., Palotie A., Peltonen L., Martin N.G., Montgomery G.W., Whitfield J.B., Visscher P.M.
Am. J. Hum. Genet. 84:60-65(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN TFQTL2.
[13]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 23-297 IN COMPLEX WITH TFR.
[14]"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] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 26-293 IN COMPLEX WITH B2MG.
[15]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-297 IN COMPLEX WITH TFR.
[16]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[17]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 TYR-282, VARIANT ASP-63.
[18]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 TYR-282, ASSOCIATION WITH PORPHYRIA CUTANEA TARDA.
[19]"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] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-63.
[20]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 TYR-282, VARIANT ASP-63.
[21]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HFE1 CYS-65 AND TYR-282, VARIANT ASP-63.
[22]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HFE1 CYS-65; ARG-93 AND THR-105.
[23]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HFE1 HIS-127 AND MET-330, VARIANTS MET-53; MET-59 AND ASP-63.
[24]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 TYR-282, VARIANT ASP-63.
[25]"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 HFE1 CYS-65.
[26]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LYS-277.
[27]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS ASP-63 AND TYR-282.
[28]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 TYR-282, VARIANT ASP-63, ASSOCIATION WITH DIABETIC NEPHROPATHY SUSCEPTIBILITY.
[29]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 VAL-176.
[30]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HFE1 CYS-65; TYR-282 AND ALA-295.
[31]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 PRO-283, CHARACTERIZATION OF VARIANT HFE1 PRO-283.
[32]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HFE1 CYS-65; CYS-66; GLY-224 AND TYR-282.
[33]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 SER-6.
[34]"Gene symbol: HFE. Disease: haemochromatosis."
Bento M.C., Ribeiro M.L., Relvas L.
Hum. Genet. 114:405-405(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HFE1 ALA-295.
[35]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT HFE1 PRO-283.
[36]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HFE1 ASP-43 AND TYR-282, VARIANT ASP-63.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
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.
AJ249335 mRNA. Translation: CAC67792.1.
AJ249336 mRNA. Translation: CAC67793.1.
AJ249337 mRNA. Translation: CAC67794.1.
AJ249338 mRNA. Translation: CAC67795.1.
AJ250635 mRNA. Translation: CAC80805.1.
EU523119 Genomic DNA. Translation: ACB21042.1.
CH471087 Genomic DNA. Translation: EAW55524.1.
CH471087 Genomic DNA. Translation: EAW55526.1.
BC117201 mRNA. Translation: AAI17202.1.
BC117203 mRNA. Translation: AAI17204.1.
CCDSCCDS4578.1. [Q30201-1]
CCDS4579.1. [Q30201-7]
CCDS4580.1. [Q30201-2]
CCDS4581.1. [Q30201-6]
CCDS4582.1. [Q30201-11]
CCDS47386.1. [Q30201-10]
CCDS47387.1. [Q30201-5]
CCDS54974.1. [Q30201-3]
CCDS54975.1. [Q30201-4]
RefSeqNP_000401.1. NM_000410.3. [Q30201-1]
NP_620572.1. NM_139003.2. [Q30201-10]
NP_620573.1. NM_139004.2. [Q30201-7]
NP_620575.1. NM_139006.2. [Q30201-3]
NP_620576.1. NM_139007.2. [Q30201-2]
NP_620577.1. NM_139008.2. [Q30201-4]
NP_620578.1. NM_139009.2. [Q30201-5]
NP_620579.1. NM_139010.2. [Q30201-6]
NP_620580.1. NM_139011.2. [Q30201-11]
UniGeneHs.233325.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A6ZX-ray2.60A/C23-297[»]
1C42model-A26-293[»]
1DE4X-ray2.80A/D/G23-297[»]
ProteinModelPortalQ30201.
SMRQ30201. Positions 26-297.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109325. 5 interactions.
DIPDIP-2737N.
IntActQ30201. 8 interactions.
MINTMINT-7896047.

PTM databases

PhosphoSiteQ30201.

Polymorphism databases

DMDM2497915.

Proteomic databases

MaxQBQ30201.
PaxDbQ30201.
PRIDEQ30201.

Protocols and materials databases

DNASU3077.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317896; ENSP00000313776; ENSG00000010704. [Q30201-7]
ENST00000336625; ENSP00000337819; ENSG00000010704. [Q30201-10]
ENST00000349999; ENSP00000259699; ENSG00000010704. [Q30201-2]
ENST00000352392; ENSP00000315936; ENSG00000010704. [Q30201-11]
ENST00000353147; ENSP00000312342; ENSG00000010704. [Q30201-6]
ENST00000357618; ENSP00000417404; ENSG00000010704. [Q30201-1]
ENST00000397022; ENSP00000380217; ENSG00000010704. [Q30201-5]
ENST00000461397; ENSP00000420802; ENSG00000010704. [Q30201-3]
ENST00000488199; ENSP00000420559; ENSG00000010704. [Q30201-4]
GeneID3077.
KEGGhsa:3077.
UCSCuc003nfx.1. human. [Q30201-1]
uc003nfy.1. human. [Q30201-5]
uc003nfz.1. human. [Q30201-2]
uc003nga.1. human. [Q30201-3]
uc003ngb.1. human. [Q30201-10]
uc003ngc.1. human. [Q30201-7]
uc003ngd.1. human. [Q30201-4]
uc003nge.1. human. [Q30201-6]
uc003ngf.1. human. [Q30201-11]

Organism-specific databases

CTD3077.
GeneCardsGC06P026087.
GeneReviewsHFE.
H-InvDBHIX0025100.
HGNCHGNC:4886. HFE.
HPAHPA017276.
MIM176200. phenotype.
235200. phenotype.
612635. phenotype.
613609. gene.
614193. phenotype.
neXtProtNX_Q30201.
Orphanet139498. Hemochromatosis type 1.
101330. Porphyria cutanea tarda.
79473. Porphyria variegata.
PharmGKBPA29263.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG41118.
HOGENOMHOG000151270.
HOVERGENHBG016709.
InParanoidQ30201.
OMAVILGCEM.
OrthoDBEOG7JT6WQ.
PhylomeDBQ30201.
TreeFamTF336617.

Gene expression databases

ArrayExpressQ30201.
BgeeQ30201.
GenevestigatorQ30201.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
3.30.500.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR011161. MHC_I-like_Ag-recog.
IPR011162. MHC_I/II-like_Ag-recog.
IPR027648. MHC_I_a.
IPR001039. MHC_I_a_a1/a2.
[Graphical view]
PfamPF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
[Graphical view]
PRINTSPR01638. MHCCLASSI.
SMARTSM00407. IGc1. 1 hit.
[Graphical view]
SUPFAMSSF54452. SSF54452. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ30201.
GeneWikiHFE_(gene).
GenomeRNAi3077.
NextBio12169.
PROQ30201.
SOURCESearch...

Entry information

Entry nameHFE_HUMAN
AccessionPrimary (citable) accession number: Q30201
Secondary accession number(s): B2CKL0 expand/collapse secondary AC list , O75929, O75930, O75931, Q17RT0, Q96KU5, Q96KU6, Q96KU7, Q96KU8, Q9HC64, Q9HC68, Q9HC70, Q9HC83
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

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