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Q30201

- HFE_HUMAN

UniProt

Q30201 - HFE_HUMAN

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Protein

Hereditary hemochromatosis protein

Gene

HFE

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.1 Publication

GO - Molecular functioni

  1. peptide antigen binding Source: InterPro
  2. receptor binding Source: UniProtKB

GO - Biological processi

  1. antigen processing and presentation of peptide antigen via MHC class I Source: UniProtKB-KW
  2. cellular iron ion homeostasis Source: ProtInc
  3. cellular response to iron ion starvation Source: Ensembl
  4. female pregnancy Source: Ensembl
  5. hormone biosynthetic process Source: Ensembl
  6. immune response Source: InterPro
  7. iron ion import into cell Source: UniProtKB
  8. multicellular organismal iron ion homeostasis Source: Ensembl
  9. positive regulation of T cell mediated cytotoxicity Source: InterPro
  10. protein complex assembly Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Immunity, Ion transport, Iron transport, Transport

Keywords - Ligandi

Iron

Names & Taxonomyi

Protein namesi
Recommended name:
Hereditary hemochromatosis protein
Alternative name(s):
HLA-H
Gene namesi
Name:HFE
Synonyms:HLAH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:4886. HFE.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 306284ExtracellularSequence AnalysisAdd
BLAST
Transmembranei307 – 33024HelicalSequence AnalysisAdd
BLAST
Topological domaini331 – 34818CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. apical part of cell Source: UniProtKB
  2. basal part of cell Source: UniProtKB
  3. cytoplasmic vesicle Source: UniProtKB
  4. early endosome Source: UniProtKB
  5. integral component of plasma membrane Source: ProtInc
  6. MHC class I protein complex Source: UniProtKB-KW
  7. perinuclear region of cytoplasm Source: UniProtKB
  8. plasma membrane Source: ProtInc
  9. recycling endosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, MHC I

Pathology & Biotechi

Involvement in diseasei

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.17 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61R → S in HFE1. 1 Publication
VAR_042506
Natural varianti43 – 431G → D in HFE1; associated with D-63 in one patient. 1 Publication
VAR_042507
Natural varianti65 – 651S → C in HFE1; mild form. 5 Publications
Corresponds to variant rs1800730 [ dbSNP | Ensembl ].
VAR_004397
Natural varianti66 – 661R → C in HFE1. 1 Publication
VAR_042508
Natural varianti93 – 931G → R in HFE1. 1 Publication
Corresponds to variant rs28934597 [ dbSNP | Ensembl ].
VAR_008729
Natural varianti105 – 1051I → T in HFE1. 1 Publication
Corresponds to variant rs28934596 [ dbSNP | Ensembl ].
VAR_008730
Natural varianti127 – 1271Q → H in HFE1. 1 Publication
Corresponds to variant rs28934595 [ dbSNP | Ensembl ].
VAR_008113
Natural varianti176 – 1761A → V in HFE1; uncertain pathological significance. 1 Publication
VAR_042509
Natural varianti224 – 2241R → G in HFE1. 1 Publication
VAR_042510
Natural varianti282 – 2821C → 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. 12 Publications
Corresponds to variant rs1800562 [ dbSNP | Ensembl ].
VAR_004398
Natural varianti283 – 2831Q → 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. 1 Publication
VAR_037304
Natural varianti295 – 2951V → A in HFE1. 2 Publications
Corresponds to variant rs143175221 [ dbSNP | Ensembl ].
VAR_042511
Natural varianti330 – 3301R → M in HFE1. 1 Publication
VAR_008114
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.

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi176200. phenotype.
235200. phenotype.
612635. phenotype.
614193. phenotype.
Orphaneti139498. Hemochromatosis type 1.
101330. Porphyria cutanea tarda.
79473. Porphyria variegata.
PharmGKBiPA29263.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Add
BLAST
Chaini23 – 348326Hereditary hemochromatosis proteinPRO_0000018892Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi110 – 1101N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi124 ↔ 187
Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi225 ↔ 282
Glycosylationi234 – 2341N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ30201.
PaxDbiQ30201.
PRIDEiQ30201.

PTM databases

PhosphoSiteiQ30201.

Expressioni

Tissue specificityi

Expressed in all tissues tested except brain.

Gene expression databases

BgeeiQ30201.
ExpressionAtlasiQ30201. baseline and differential.
GenevestigatoriQ30201.

Organism-specific databases

HPAiHPA017276.

Interactioni

Subunit structurei

Binds TFR through the extracellular domain in a pH-dependent manner.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
B2MP617693EBI-1028850,EBI-714718

Protein-protein interaction databases

BioGridi109325. 5 interactions.
DIPiDIP-2737N.
IntActiQ30201. 8 interactions.
MINTiMINT-7896047.

Structurei

Secondary structure

1
348
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi28 – 3811Combined sources
Beta strandi43 – 453Combined sources
Beta strandi48 – 536Combined sources
Beta strandi56 – 6510Combined sources
Beta strandi68 – 703Combined sources
Helixi75 – 784Combined sources
Turni79 – 824Combined sources
Helixi83 – 10725Combined sources
Turni108 – 1103Combined sources
Beta strandi112 – 1143Combined sources
Beta strandi117 – 12610Combined sources
Beta strandi132 – 1409Combined sources
Beta strandi143 – 1497Combined sources
Helixi150 – 1523Combined sources
Beta strandi154 – 1596Combined sources
Helixi160 – 1623Combined sources
Helixi163 – 1708Combined sources
Helixi174 – 18411Combined sources
Helixi186 – 19813Combined sources
Turni199 – 2013Combined sources
Beta strandi209 – 2168Combined sources
Beta strandi221 – 23313Combined sources
Beta strandi236 – 2416Combined sources
Helixi248 – 2503Combined sources
Beta strandi255 – 2584Combined sources
Beta strandi264 – 2729Combined sources
Helixi276 – 2794Combined sources
Beta strandi280 – 2856Combined sources
Beta strandi289 – 2913Combined sources
Beta strandi293 – 2964Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A6ZX-ray2.60A/C23-297[»]
1C42model-A26-293[»]
1DE4X-ray2.80A/D/G23-297[»]
ProteinModelPortaliQ30201.
SMRiQ30201. Positions 26-297.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ30201.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini207 – 29892Ig-like C1-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni23 – 11492Alpha-1Add
BLAST
Regioni115 – 20591Alpha-2Add
BLAST
Regioni206 – 29792Alpha-3Add
BLAST
Regioni298 – 3069Connecting peptide

Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG41118.
GeneTreeiENSGT00760000118960.
HOGENOMiHOG000151270.
HOVERGENiHBG016709.
InParanoidiQ30201.
OMAiVILGCEM.
OrthoDBiEOG7JT6WQ.
PhylomeDBiQ30201.
TreeFamiTF336617.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.30.500.10. 1 hit.
InterProiIPR007110. 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]
PfamiPF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
[Graphical view]
PRINTSiPR01638. MHCCLASSI.
SMARTiSM00407. IGc1. 1 hit.
[Graphical view]
SUPFAMiSSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

Sequences (11)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 11 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q30201-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGPRARPALL LLMLLQTAVL QGRLLRSHSL HYLFMGASEQ DLGLSLFEAL
60 70 80 90 100
GYVDDQLFVF YDHESRRVEP RTPWVSSRIS SQMWLQLSQS LKGWDHMFTV
110 120 130 140 150
DFWTIMENHN HSKESHTLQV ILGCEMQEDN STEGYWKYGY DGQDHLEFCP
160 170 180 190 200
DTLDWRAAEP RAWPTKLEWE RHKIRARQNR AYLERDCPAQ LQQLLELGRG
210 220 230 240 250
VLDQQVPPLV KVTHHVTSSV TTLRCRALNY YPQNITMKWL KDKQPMDAKE
260 270 280 290 300
FEPKDVLPNG DGTYQGWITL AVPPGEEQRY TCQVEHPGLD QPLIVIWEPS
310 320 330 340
PSGTLVIGVI SGIAVFVVIL FIGILFIILR KRQGSRGAMG HYVLAERE

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Length:348
Mass (Da):40,108
Last modified:November 1, 1997 - v1
Checksum:i432EB9A314A55BEA
GO
Isoform 2 (identifier: Q30201-2) [UniParc]FASTAAdd to Basket

Also known as: delE2

The sequence of this isoform differs from the canonical sequence as follows:
     26-114: RSHSLHYLFM...IMENHNHSKE → Q

Show »
Length:260
Mass (Da):29,633
Checksum:iC30AC94F06A81AAA
GO
Isoform 3 (identifier: Q30201-3) [UniParc]FASTAAdd to Basket

Also known as: del14E4

The sequence of this isoform differs from the canonical sequence as follows:
     207-220: Missing.

Show »
Length:334
Mass (Da):38,625
Checksum:i811D9D68BB9D7F3A
GO
Isoform 4 (identifier: Q30201-4) [UniParc]FASTAAdd to Basket

Also known as: delE214E4

The sequence of this isoform differs from the canonical sequence as follows:
     26-114: RSHSLHYLFM...IMENHNHSKE → Q
     207-220: Missing.

Show »
Length:246
Mass (Da):28,151
Checksum:i47B79FE7B8B49A0A
GO
Isoform 5 (identifier: Q30201-5) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     26-49: RSHSLHYLFMGASEQDLGLSLFEA → P

Show »
Length:325
Mass (Da):37,514
Checksum:i626343ACFAA862EF
GO
Isoform 6 (identifier: Q30201-6) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     26-26: R → L
     27-206: Missing.

Show »
Length:168
Mass (Da):18,734
Checksum:i525C7094CEE850F9
GO
Isoform 7 (identifier: Q30201-7) [UniParc]FASTAAdd to Basket

Also known as: delE3

The sequence of this isoform differs from the canonical sequence as follows:
     114-205: Missing.

Show »
Length:256
Mass (Da):29,194
Checksum:i0E810B1BBACDF0BF
GO
Isoform 8 (identifier: Q30201-8) [UniParc]FASTAAdd to Basket

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.

Show »
Length:276
Mass (Da):32,243
Checksum:i3E0D2762D7476B82
GO
Isoform 9 (identifier: Q30201-9) [UniParc]FASTAAdd to Basket

Also known as: delE3-7

The sequence of this isoform differs from the canonical sequence as follows:
     144-161: DHLEFCPDTLDWRAAEPR → VLQDTIYSSEVSSLGIKF
     162-348: Missing.

Show »
Length:161
Mass (Da):18,651
Checksum:i5E288C5835DC3784
GO
Isoform 10 (identifier: Q30201-10) [UniParc]FASTAAdd to Basket

Also known as: 562-878del

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

Show »
Length:242
Mass (Da):27,711
Checksum:iE423FF903128DB74
GO
Isoform 11 (identifier: Q30201-11) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     26-26: R → Q
     27-298: Missing.

Note: No experimental confirmation available.

Show »
Length:76
Mass (Da):8,208
Checksum:iB56810C036B9BEE9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti230 – 2301Y → H in AAG29342. (PubMed:11358357)Curated
Sequence conflicti248 – 2481A → T in AAG29575. (PubMed:11358357)Curated
Sequence conflicti256 – 2561V → A in AAG29577. (PubMed:11358357)Curated
Sequence conflicti275 – 2751G → E in AAG29342. (PubMed:11358357)Curated
Sequence conflicti311 – 3111S → R in AAG29342. (PubMed:11358357)Curated
Sequence conflicti339 – 3391M → V in AAG29577. (PubMed:11358357)Curated

Polymorphismi

Genetic variations in HFE define the transferrin serum level quantitative trait locus 2 (TFQTL2) [MIMi: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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61R → S in HFE1. 1 Publication
VAR_042506
Natural varianti43 – 431G → D in HFE1; associated with D-63 in one patient. 1 Publication
VAR_042507
Natural varianti53 – 531V → M.2 Publications
Corresponds to variant rs28934889 [ dbSNP | Ensembl ].
VAR_008111
Natural varianti59 – 591V → M.1 Publication
Corresponds to variant rs28934890 [ dbSNP | Ensembl ].
VAR_008112
Natural varianti63 – 631H → D Polymorphism associated with hemochromatosis and variegate porphyria; increased frequency among patients with diabetic nephropathy. 11 Publications
Corresponds to variant rs1799945 [ dbSNP | Ensembl ].
VAR_004396
Natural varianti65 – 651S → C in HFE1; mild form. 5 Publications
Corresponds to variant rs1800730 [ dbSNP | Ensembl ].
VAR_004397
Natural varianti66 – 661R → C in HFE1. 1 Publication
VAR_042508
Natural varianti93 – 931G → R in HFE1. 1 Publication
Corresponds to variant rs28934597 [ dbSNP | Ensembl ].
VAR_008729
Natural varianti105 – 1051I → T in HFE1. 1 Publication
Corresponds to variant rs28934596 [ dbSNP | Ensembl ].
VAR_008730
Natural varianti127 – 1271Q → H in HFE1. 1 Publication
Corresponds to variant rs28934595 [ dbSNP | Ensembl ].
VAR_008113
Natural varianti176 – 1761A → V in HFE1; uncertain pathological significance. 1 Publication
VAR_042509
Natural varianti217 – 2171T → I.
Corresponds to variant rs4986950 [ dbSNP | Ensembl ].
VAR_020270
Natural varianti224 – 2241R → G in HFE1. 1 Publication
VAR_042510
Natural varianti224 – 2241R → Q.1 Publication
Corresponds to variant rs62625346 [ dbSNP | Ensembl ].
VAR_062279
Natural varianti277 – 2771E → K Rare polymorphism. 1 Publication
Corresponds to variant rs140080192 [ dbSNP | Ensembl ].
VAR_008731
Natural varianti282 – 2821C → 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. 12 Publications
Corresponds to variant rs1800562 [ dbSNP | Ensembl ].
VAR_004398
Natural varianti283 – 2831Q → 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. 1 Publication
VAR_037304
Natural varianti295 – 2951V → A in HFE1. 2 Publications
Corresponds to variant rs143175221 [ dbSNP | Ensembl ].
VAR_042511
Natural varianti330 – 3301R → M in HFE1. 1 Publication
VAR_008114

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei26 – 11489RSHSL…NHSKE → Q in isoform 2 and isoform 4. 2 PublicationsVSP_003218Add
BLAST
Alternative sequencei26 – 4924RSHSL…SLFEA → P in isoform 5. 1 PublicationVSP_003219Add
BLAST
Alternative sequencei26 – 261R → Q in isoform 11. 1 PublicationVSP_043477
Alternative sequencei26 – 261R → L in isoform 6. 1 PublicationVSP_047336
Alternative sequencei27 – 298272Missing in isoform 11. 1 PublicationVSP_043478Add
BLAST
Alternative sequencei27 – 206180Missing in isoform 6. 1 PublicationVSP_003220Add
BLAST
Alternative sequencei114 – 219106Missing in isoform 10. 1 PublicationVSP_003222Add
BLAST
Alternative sequencei114 – 20592Missing in isoform 7. 2 PublicationsVSP_003221Add
BLAST
Alternative sequencei144 – 16118DHLEF…AAEPR → VLQDTIYSSEVSSLGIKF in isoform 9. 1 PublicationVSP_003223Add
BLAST
Alternative sequencei162 – 348187Missing in isoform 9. 1 PublicationVSP_003224Add
BLAST
Alternative sequencei207 – 22014Missing in isoform 3 and isoform 4. 1 PublicationVSP_003225Add
BLAST
Alternative sequencei275 – 2762GE → KY in isoform 8. 1 PublicationVSP_003226
Alternative sequencei277 – 34872Missing in isoform 8. 1 PublicationVSP_003227Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U60319 mRNA. Translation: AAC51823.1.
U91328 Genomic DNA. Translation: AAB82083.1.
Z92910 Genomic DNA. Translation: CAB07442.1.
Y09801
, 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.
CCDSiCCDS4578.1. [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]
RefSeqiNP_000401.1. NM_000410.3. [Q30201-1]
NP_001287678.1. NM_001300749.1.
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]
UniGeneiHs.233325.

Genome annotation databases

EnsembliENST00000317896; 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]
GeneIDi3077.
KEGGihsa:3077.
UCSCiuc003nfx.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]

Polymorphism databases

DMDMi2497915.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U60319 mRNA. Translation: AAC51823.1 .
U91328 Genomic DNA. Translation: AAB82083.1 .
Z92910 Genomic DNA. Translation: CAB07442.1 .
Y09801
, 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 .
CCDSi CCDS4578.1. [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 ]
RefSeqi NP_000401.1. NM_000410.3. [Q30201-1 ]
NP_001287678.1. NM_001300749.1.
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 ]
UniGenei Hs.233325.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1A6Z X-ray 2.60 A/C 23-297 [» ]
1C42 model - A 26-293 [» ]
1DE4 X-ray 2.80 A/D/G 23-297 [» ]
ProteinModelPortali Q30201.
SMRi Q30201. Positions 26-297.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109325. 5 interactions.
DIPi DIP-2737N.
IntActi Q30201. 8 interactions.
MINTi MINT-7896047.

PTM databases

PhosphoSitei Q30201.

Polymorphism databases

DMDMi 2497915.

Proteomic databases

MaxQBi Q30201.
PaxDbi Q30201.
PRIDEi Q30201.

Protocols and materials databases

DNASUi 3077.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000317896 ; 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 ]
GeneIDi 3077.
KEGGi hsa:3077.
UCSCi uc003nfx.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

CTDi 3077.
GeneCardsi GC06P026087.
GeneReviewsi HFE.
H-InvDB HIX0025100.
HGNCi HGNC:4886. HFE.
HPAi HPA017276.
MIMi 176200. phenotype.
235200. phenotype.
612635. phenotype.
613609. gene.
614193. phenotype.
neXtProti NX_Q30201.
Orphaneti 139498. Hemochromatosis type 1.
101330. Porphyria cutanea tarda.
79473. Porphyria variegata.
PharmGKBi PA29263.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG41118.
GeneTreei ENSGT00760000118960.
HOGENOMi HOG000151270.
HOVERGENi HBG016709.
InParanoidi Q30201.
OMAi VILGCEM.
OrthoDBi EOG7JT6WQ.
PhylomeDBi Q30201.
TreeFami TF336617.

Miscellaneous databases

EvolutionaryTracei Q30201.
GeneWikii HFE_(gene).
GenomeRNAii 3077.
NextBioi 12169.
PROi Q30201.
SOURCEi Search...

Gene expression databases

Bgeei Q30201.
ExpressionAtlasi Q30201. baseline and differential.
Genevestigatori Q30201.

Family and domain databases

Gene3Di 2.60.40.10. 1 hit.
3.30.500.10. 1 hit.
InterProi IPR007110. 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 ]
Pfami PF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
[Graphical view ]
PRINTSi PR01638. MHCCLASSI.
SMARTi SM00407. IGc1. 1 hit.
[Graphical view ]
SUPFAMi SSF54452. SSF54452. 1 hit.
PROSITEi PS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT HFE1 TYR-282, VARIANT ASP-63.
  2. 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. 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. 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. 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. 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. 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.

Entry informationi

Entry nameiHFE_HUMAN
AccessioniPrimary (citable) accession number: Q30201
Secondary accession number(s): B2CKL0
, O75929, O75930, O75931, Q17RT0, Q96KU5, Q96KU6, Q96KU7, Q96KU8, Q9HC64, Q9HC68, Q9HC70, Q9HC83
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 26, 2014
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3