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Protein

Hereditary hemochromatosis protein

Gene

HFE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • antigen binding Source: GO_Central
  • beta-2-microglobulin binding Source: BHF-UCL
  • co-receptor binding Source: BHF-UCL
  • receptor binding Source: UniProtKB
  • transferrin receptor binding Source: BHF-UCL

GO - Biological processi

  • acute-phase response Source: Ensembl
  • BMP signaling pathway Source: BHF-UCL
  • cellular iron ion homeostasis Source: ProtInc
  • cellular response to iron ion Source: BHF-UCL
  • cellular response to iron ion starvation Source: Ensembl
  • female pregnancy Source: Ensembl
  • hormone biosynthetic process Source: Ensembl
  • iron ion homeostasis Source: BHF-UCL
  • iron ion import into cell Source: UniProtKB
  • liver regeneration Source: Ensembl
  • multicellular organismal iron ion homeostasis Source: Ensembl
  • negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I Source: BHF-UCL
  • negative regulation of CD8-positive, alpha-beta T cell activation Source: BHF-UCL
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • negative regulation of receptor activity Source: BHF-UCL
  • negative regulation of receptor binding Source: BHF-UCL
  • negative regulation of T cell antigen processing and presentation Source: InterPro
  • negative regulation of T cell cytokine production Source: BHF-UCL
  • positive regulation of ferrous iron binding Source: BHF-UCL
  • positive regulation of ferrous iron import into cell Source: BHF-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • positive regulation of peptide hormone secretion Source: BHF-UCL
  • positive regulation of protein binding Source: BHF-UCL
  • positive regulation of receptor activity Source: BHF-UCL
  • positive regulation of receptor binding Source: BHF-UCL
  • positive regulation of receptor-mediated endocytosis Source: BHF-UCL
  • positive regulation of transferrin receptor binding Source: BHF-UCL
  • protein complex assembly Source: ProtInc
  • regulation of protein localization to cell surface Source: BHF-UCL
  • response to iron ion Source: BHF-UCL
  • response to iron ion starvation Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Ion transport, Iron transport, Transport

Keywords - Ligandi

Iron

Enzyme and pathway databases

BioCyciZFISH:ENSG00000010704-MONOMER.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4886. HFE.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 306Extracellular1 PublicationAdd BLAST284
Transmembranei307 – 330HelicalSequence analysisAdd BLAST24
Topological domaini331 – 348Cytoplasmic1 PublicationAdd BLAST18

GO - Cellular componenti

  • apical part of cell Source: UniProtKB
  • basal part of cell Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB
  • early endosome Source: UniProtKB
  • external side of plasma membrane Source: BHF-UCL
  • extracellular space Source: BHF-UCL
  • HFE-transferrin receptor complex Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: ProtInc
  • recycling endosome Source: UniProtKB
  • terminal web Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hemochromatosis 1 (HFE1)17 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:235200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0425066R → S in HFE1. 1 PublicationCorresponds to variant rs149342416dbSNPEnsembl.1
Natural variantiVAR_04250743G → D in HFE1; associated with D-63 in one patient. 1 Publication1
Natural variantiVAR_00439765S → C in HFE1; mild form. 5 PublicationsCorresponds to variant rs1800730dbSNPEnsembl.1
Natural variantiVAR_04250866R → C in HFE1. 1 PublicationCorresponds to variant rs747739169dbSNPEnsembl.1
Natural variantiVAR_00872993G → R in HFE1. 1 PublicationCorresponds to variant rs28934597dbSNPEnsembl.1
Natural variantiVAR_008730105I → T in HFE1. 1 PublicationCorresponds to variant rs28934596dbSNPEnsembl.1
Natural variantiVAR_008113127Q → H in HFE1. 1 PublicationCorresponds to variant rs28934595dbSNPEnsembl.1
Natural variantiVAR_042509176A → V in HFE1; uncertain pathological significance. 1 Publication1
Natural variantiVAR_042510224R → G in HFE1. 1 Publication1
Natural variantiVAR_004398282C → 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 PublicationsCorresponds to variant rs1800562dbSNPEnsembl.1
Natural variantiVAR_037304283Q → 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. 2 PublicationsCorresponds to variant rs111033563dbSNPEnsembl.1
Natural variantiVAR_042511295V → A in HFE1. 2 PublicationsCorresponds to variant rs143175221dbSNPEnsembl.1
Natural variantiVAR_008114330R → M in HFE1. 1 PublicationCorresponds to variant rs111033558dbSNPEnsembl.1
Variegate porphyria (VP)
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.
Disease descriptionA 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.
See also OMIM:176200
Microvascular complications of diabetes 7 (MVCD7)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionPathological 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.
See also OMIM:612635

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3077.
MalaCardsiHFE.
MIMi176200. phenotype.
235200. phenotype.
612635. phenotype.
614193. phenotype.
OpenTargetsiENSG00000010704.
Orphaneti139498. Hemochromatosis type 1.
101330. Porphyria cutanea tarda.
79473. Porphyria variegata.
PharmGKBiPA29263.

Polymorphism and mutation databases

BioMutaiHFE.
DMDMi2497915.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Add BLAST22
ChainiPRO_000001889223 – 348Hereditary hemochromatosis proteinAdd BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi110N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi124 ↔ 187
Glycosylationi130N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi225 ↔ 282
Glycosylationi234N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ30201.
PaxDbiQ30201.
PeptideAtlasiQ30201.
PRIDEiQ30201.
TopDownProteomicsiQ30201-1. [Q30201-1]

PTM databases

iPTMnetiQ30201.
PhosphoSitePlusiQ30201.

Expressioni

Tissue specificityi

Expressed in all tissues tested except brain.

Gene expression databases

BgeeiENSG00000010704.
ExpressionAtlasiQ30201. baseline and differential.
GenevisibleiQ30201. HS.

Organism-specific databases

HPAiHPA017276.
HPA053470.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
B2MP617695EBI-1028850,EBI-714718
TFRCP027863EBI-1028850,EBI-355727

GO - Molecular functioni

  • beta-2-microglobulin binding Source: BHF-UCL
  • co-receptor binding Source: BHF-UCL
  • receptor binding Source: UniProtKB
  • transferrin receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109325. 3 interactors.
DIPiDIP-2737N.
IntActiQ30201. 8 interactors.
MINTiMINT-7896047.
STRINGi9606.ENSP00000417404.

Structurei

Secondary structure

1348
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 38Combined sources11
Beta strandi43 – 45Combined sources3
Beta strandi48 – 53Combined sources6
Beta strandi56 – 65Combined sources10
Beta strandi68 – 70Combined sources3
Helixi75 – 78Combined sources4
Turni79 – 82Combined sources4
Helixi83 – 107Combined sources25
Turni108 – 110Combined sources3
Beta strandi112 – 114Combined sources3
Beta strandi117 – 126Combined sources10
Beta strandi132 – 140Combined sources9
Beta strandi143 – 149Combined sources7
Helixi150 – 152Combined sources3
Beta strandi154 – 159Combined sources6
Helixi160 – 162Combined sources3
Helixi163 – 170Combined sources8
Helixi174 – 184Combined sources11
Helixi186 – 198Combined sources13
Turni199 – 201Combined sources3
Beta strandi209 – 216Combined sources8
Beta strandi221 – 233Combined sources13
Beta strandi236 – 241Combined sources6
Helixi248 – 250Combined sources3
Beta strandi255 – 258Combined sources4
Beta strandi264 – 272Combined sources9
Helixi276 – 279Combined sources4
Beta strandi280 – 285Combined sources6
Beta strandi289 – 291Combined sources3
Beta strandi293 – 296Combined sources4

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ30201.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini207 – 298Ig-like C1-typeAdd BLAST92

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni23 – 114Alpha-1Add BLAST92
Regioni115 – 205Alpha-2Add BLAST91
Regioni206 – 297Alpha-3Add BLAST92
Regioni298 – 306Connecting peptide9

Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFNV. Eukaryota.
ENOG4111CQR. LUCA.
GeneTreeiENSGT00760000118960.
HOGENOMiHOG000151270.
HOVERGENiHBG016709.
InParanoidiQ30201.
OMAiCEMQEDN.
OrthoDBiEOG091G0K1X.
PhylomeDBiQ30201.
TreeFamiTF336617.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.30.500.10. 1 hit.
InterProiIPR031092. HFE.
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.
IPR001039. MHC_I_a_a1/a2.
[Graphical view]
PANTHERiPTHR16675:SF172. PTHR16675:SF172. 1 hit.
PfamiPF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
[Graphical view]
PRINTSiPR01638. MHCCLASSI.
SMARTiSM00407. IGc1. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. 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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti230Y → H in AAG29342 (PubMed:11358357).Curated1
Sequence conflicti248A → T in AAG29575 (PubMed:11358357).Curated1
Sequence conflicti256V → A in AAG29577 (PubMed:11358357).Curated1
Sequence conflicti275G → E in AAG29342 (PubMed:11358357).Curated1
Sequence conflicti311S → R in AAG29342 (PubMed:11358357).Curated1
Sequence conflicti339M → V in AAG29577 (PubMed:11358357).Curated1

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_0425066R → S in HFE1. 1 PublicationCorresponds to variant rs149342416dbSNPEnsembl.1
Natural variantiVAR_04250743G → D in HFE1; associated with D-63 in one patient. 1 Publication1
Natural variantiVAR_00811153V → M.2 PublicationsCorresponds to variant rs28934889dbSNPEnsembl.1
Natural variantiVAR_00811259V → M.1 PublicationCorresponds to variant rs28934890dbSNPEnsembl.1
Natural variantiVAR_00439663H → D Polymorphism associated with hemochromatosis and variegate porphyria; increased frequency among patients with diabetic nephropathy. 11 PublicationsCorresponds to variant rs1799945dbSNPEnsembl.1
Natural variantiVAR_00439765S → C in HFE1; mild form. 5 PublicationsCorresponds to variant rs1800730dbSNPEnsembl.1
Natural variantiVAR_04250866R → C in HFE1. 1 PublicationCorresponds to variant rs747739169dbSNPEnsembl.1
Natural variantiVAR_00872993G → R in HFE1. 1 PublicationCorresponds to variant rs28934597dbSNPEnsembl.1
Natural variantiVAR_008730105I → T in HFE1. 1 PublicationCorresponds to variant rs28934596dbSNPEnsembl.1
Natural variantiVAR_008113127Q → H in HFE1. 1 PublicationCorresponds to variant rs28934595dbSNPEnsembl.1
Natural variantiVAR_042509176A → V in HFE1; uncertain pathological significance. 1 Publication1
Natural variantiVAR_020270217T → I.Corresponds to variant rs4986950dbSNPEnsembl.1
Natural variantiVAR_042510224R → G in HFE1. 1 Publication1
Natural variantiVAR_062279224R → Q.1 PublicationCorresponds to variant rs62625346dbSNPEnsembl.1
Natural variantiVAR_008731277E → K Rare polymorphism. 1 PublicationCorresponds to variant rs140080192dbSNPEnsembl.1
Natural variantiVAR_004398282C → 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 PublicationsCorresponds to variant rs1800562dbSNPEnsembl.1
Natural variantiVAR_037304283Q → 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. 2 PublicationsCorresponds to variant rs111033563dbSNPEnsembl.1
Natural variantiVAR_042511295V → A in HFE1. 2 PublicationsCorresponds to variant rs143175221dbSNPEnsembl.1
Natural variantiVAR_008114330R → M in HFE1. 1 PublicationCorresponds to variant rs111033558dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00321826 – 114RSHSL…NHSKE → Q in isoform 2 and isoform 4. 2 PublicationsAdd BLAST89
Alternative sequenceiVSP_00321926 – 49RSHSL…SLFEA → P in isoform 5. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_04347726R → Q in isoform 11. 1 Publication1
Alternative sequenceiVSP_04733626R → L in isoform 6. 1 Publication1
Alternative sequenceiVSP_04347827 – 298Missing in isoform 11. 1 PublicationAdd BLAST272
Alternative sequenceiVSP_00322027 – 206Missing in isoform 6. 1 PublicationAdd BLAST180
Alternative sequenceiVSP_003222114 – 219Missing in isoform 10. 1 PublicationAdd BLAST106
Alternative sequenceiVSP_003221114 – 205Missing in isoform 7. 2 PublicationsAdd BLAST92
Alternative sequenceiVSP_003223144 – 161DHLEF…AAEPR → VLQDTIYSSEVSSLGIKF in isoform 9. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_003224162 – 348Missing in isoform 9. 1 PublicationAdd BLAST187
Alternative sequenceiVSP_003225207 – 220Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_003226275 – 276GE → KY in isoform 8. 1 Publication2
Alternative sequenceiVSP_003227277 – 348Missing in isoform 8. 1 PublicationAdd BLAST72

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.2. human. [Q30201-1]

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.
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi109325. 3 interactors.
DIPiDIP-2737N.
IntActiQ30201. 8 interactors.
MINTiMINT-7896047.
STRINGi9606.ENSP00000417404.

PTM databases

iPTMnetiQ30201.
PhosphoSitePlusiQ30201.

Polymorphism and mutation databases

BioMutaiHFE.
DMDMi2497915.

Proteomic databases

MaxQBiQ30201.
PaxDbiQ30201.
PeptideAtlasiQ30201.
PRIDEiQ30201.
TopDownProteomicsiQ30201-1. [Q30201-1]

Protocols and materials databases

DNASUi3077.
Structural Biology KnowledgebaseSearch...

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.2. human. [Q30201-1]

Organism-specific databases

CTDi3077.
DisGeNETi3077.
GeneCardsiHFE.
GeneReviewsiHFE.
H-InvDBHIX0025100.
HGNCiHGNC:4886. HFE.
HPAiHPA017276.
HPA053470.
MalaCardsiHFE.
MIMi176200. phenotype.
235200. phenotype.
612635. phenotype.
613609. gene.
614193. phenotype.
neXtProtiNX_Q30201.
OpenTargetsiENSG00000010704.
Orphaneti139498. Hemochromatosis type 1.
101330. Porphyria cutanea tarda.
79473. Porphyria variegata.
PharmGKBiPA29263.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFNV. Eukaryota.
ENOG4111CQR. LUCA.
GeneTreeiENSGT00760000118960.
HOGENOMiHOG000151270.
HOVERGENiHBG016709.
InParanoidiQ30201.
OMAiCEMQEDN.
OrthoDBiEOG091G0K1X.
PhylomeDBiQ30201.
TreeFamiTF336617.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000010704-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ30201.
GeneWikiiHFE_(gene).
GenomeRNAii3077.
PROiQ30201.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000010704.
ExpressionAtlasiQ30201. baseline and differential.
GenevisibleiQ30201. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.30.500.10. 1 hit.
InterProiIPR031092. HFE.
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.
IPR001039. MHC_I_a_a1/a2.
[Graphical view]
PANTHERiPTHR16675:SF172. PTHR16675:SF172. 1 hit.
PfamiPF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
[Graphical view]
PRINTSiPR01638. MHCCLASSI.
SMARTiSM00407. IGc1. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

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 2, 2016
This is version 181 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.