Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hemojuvelin

Gene

HFE2

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

Functioni

Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis.By similarity

GO - Molecular functioni

  • BMP binding Source: BHF-UCL
  • coreceptor activity Source: BHF-UCL
  • glycoprotein binding Source: BHF-UCL
  • receptor binding Source: BHF-UCL
  • transferrin receptor binding Source: BHF-UCL

GO - Biological processi

  • activin receptor signaling pathway Source: BHF-UCL
  • BMP signaling pathway Source: BHF-UCL
  • cellular iron ion homeostasis Source: BHF-UCL
  • cellular response to BMP stimulus Source: BHF-UCL
  • iron ion homeostasis Source: MGI
  • negative regulation of BMP signaling pathway Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • protein autoprocessing Source: BHF-UCL
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-373752. Netrin-1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Hemojuvelin
Alternative name(s):
Hemochromatosis type 2 protein
RGM domain family member C
Gene namesi
Name:HFE2
Synonyms:HJV, RGMC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:4887. HFE2.

Subcellular locationi

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • BMP receptor complex Source: BHF-UCL
  • cell surface Source: Ensembl
  • extracellular space Source: UniProtKB
  • HFE-transferrin receptor complex Source: BHF-UCL
  • plasma membrane Source: BHF-UCL
  • plasma membrane protein complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hemochromatosis 2A (HFE2A)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA juvenile form of hemochromatosis, a disorder of iron metabolism with excess deposition of iron in a variety of organs leading to their failure, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of juvenile hemochromatosis at presentation are hypogonadism and cardiomyopathy.
See also OMIM:602390
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01961780C → R in HFE2A. 1 PublicationCorresponds to variant rs28940586dbSNPEnsembl.1
Natural variantiVAR_01961885S → P in HFE2A. 1 Publication1
Natural variantiVAR_01961999G → R in HFE2A. 1 Publication1
Natural variantiVAR_019620101L → P in HFE2A. 1 PublicationCorresponds to variant rs74315327dbSNPEnsembl.1
Natural variantiVAR_019621168A → D in HFE2A. 1 PublicationCorresponds to variant rs782125244dbSNPEnsembl.1
Natural variantiVAR_019622170F → S in HFE2A. 1 Publication1
Natural variantiVAR_019623172D → E in HFE2A. 1 PublicationCorresponds to variant rs782708481dbSNPEnsembl.1
Natural variantiVAR_019624191W → C in HFE2A. 1 Publication1
Natural variantiVAR_019625205S → R in HFE2A. 1 Publication1
Natural variantiVAR_019626222I → N in HFE2A. 2 PublicationsCorresponds to variant rs74315325dbSNPEnsembl.1
Natural variantiVAR_019627250G → V in HFE2A. 1 Publication1
Natural variantiVAR_019628288R → W in HFE2A. 1 Publication1
Natural variantiVAR_019629320G → V in HFE2A. 4 PublicationsCorresponds to variant rs74315323dbSNPEnsembl.1
Natural variantiVAR_019927321C → W in HFE2A. 1 PublicationCorresponds to variant rs121434374dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi148738.
MalaCardsiHFE2.
MIMi602390. phenotype.
OpenTargetsiENSG00000168509.
Orphaneti79230. Hemochromatosis type 2.
PharmGKBiPA29264.

Polymorphism and mutation databases

BioMutaiHFE2.
DMDMi51316254.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 35Sequence analysisAdd BLAST35
ChainiPRO_000003039836 – 400HemojuvelinAdd BLAST365
PropeptideiPRO_0000030399401 – 426Removed in mature formSequence analysisAdd BLAST26

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46PhosphotyrosineBy similarity1
Glycosylationi118N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi148 ↔ 230By similarity
Disulfide bondi167 ↔ 317By similarity
Glycosylationi213N-linked (GlcNAc...)Sequence analysis1
Glycosylationi372N-linked (GlcNAc...)Sequence analysis1
Lipidationi400GPI-anchor amidated aspartateSequence analysis1

Post-translational modificationi

Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds. Also proteolytically processed by TMPRSS6, several fragments being released in the extracellular space; regulates HFE2 activity in BMP signaling and thefore iron homeostasis.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei172 – 173Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ6ZVN8.
PeptideAtlasiQ6ZVN8.
PRIDEiQ6ZVN8.

PTM databases

iPTMnetiQ6ZVN8.
PhosphoSitePlusiQ6ZVN8.

Expressioni

Tissue specificityi

Adult and fetal liver, heart, and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000168509.
CleanExiHS_HFE2.
ExpressionAtlasiQ6ZVN8. baseline and differential.
GenevisibleiQ6ZVN8. HS.

Interactioni

Subunit structurei

Interacts with BMP2 and BMP4 (By similarity). Interacts with BMPR1B. Interacts with TMPRSS6.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BMP2P126432EBI-10900704,EBI-1029262
NEO1Q928593EBI-10900704,EBI-2829116
TMPRSS6Q8IU80-43EBI-10900704,EBI-11686560

GO - Molecular functioni

  • BMP binding Source: BHF-UCL
  • receptor binding Source: BHF-UCL
  • transferrin receptor binding Source: BHF-UCL

Protein-protein interaction databases

DIPiDIP-61608N.
IntActiQ6ZVN8. 4 interactors.
STRINGi9606.ENSP00000337014.

Structurei

Secondary structure

1426
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi39 – 51Combined sources13
Helixi78 – 93Combined sources16
Helixi94 – 96Combined sources3
Helixi101 – 116Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UI1X-ray2.35C/D35-145[»]
ProteinModelPortaliQ6ZVN8.
SMRiQ6ZVN8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi64 – 78Poly-GlyAdd BLAST15
Compositional biasi127 – 130Poly-Pro4

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFAH. Eukaryota.
ENOG410ZT7E. LUCA.
GeneTreeiENSGT00390000008488.
HOGENOMiHOG000013072.
HOVERGENiHBG057627.
InParanoidiQ6ZVN8.
KOiK06847.
OMAiRFSRLHG.
OrthoDBiEOG091G0NF6.
PhylomeDBiQ6ZVN8.
TreeFamiTF329836.

Family and domain databases

InterProiIPR033606. Hemojuvelin.
IPR009496. RGM_C.
IPR010536. RGM_N.
[Graphical view]
PANTHERiPTHR31428:SF3. PTHR31428:SF3. 1 hit.
PfamiPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform a (identifier: Q6ZVN8-1) [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
MGEPGQSPSP RSSHGSPPTL STLTLLLLLC GHAHSQCKIL RCNAEYVSST
60 70 80 90 100
LSLRGGGSSG ALRGGGGGGR GGGVGSGGLC RALRSYALCT RRTARTCRGD
110 120 130 140 150
LAFHSAVHGI EDLMIQHNCS RQGPTAPPPP RGPALPGAGS GLPAPDPCDY
160 170 180 190 200
EGRFSRLHGR PPGFLHCASF GDPHVRSFHH HFHTCRVQGA WPLLDNDFLF
210 220 230 240 250
VQATSSPMAL GANATATRKL TIIFKNMQEC IDQKVYQAEV DNLPVAFEDG
260 270 280 290 300
SINGGDRPGG SSLSIQTANP GNHVEIQAAY IGTTIIIRQT AGQLSFSIKV
310 320 330 340 350
AEDVAMAFSA EQDLQLCVGG CPPSQRLSRS ERNRRGAITI DTARRLCKEG
360 370 380 390 400
LPVEDAYFHS CVFDVLISGD PNFTVAAQAA LEDARAFLPD LEKLHLFPSD
410 420
AGVPLSSATL LAPLLSGLFV LWLCIQ
Length:426
Mass (Da):45,080
Last modified:July 5, 2004 - v1
Checksum:i031C835F9B6DC06C
GO
Isoform b (identifier: Q6ZVN8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-113: Missing.

Show »
Length:313
Mass (Da):33,679
Checksum:i0B056ED5D92B26E6
GO
Isoform c (identifier: Q6ZVN8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-226: Missing.

Show »
Length:200
Mass (Da):21,463
Checksum:i7A7F39D3AD7F8CC5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69G → GG in ABC40718 (Ref. 3) Curated1
Sequence conflicti299K → E in BAC03944 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01961780C → R in HFE2A. 1 PublicationCorresponds to variant rs28940586dbSNPEnsembl.1
Natural variantiVAR_01961885S → P in HFE2A. 1 Publication1
Natural variantiVAR_01961999G → R in HFE2A. 1 Publication1
Natural variantiVAR_019620101L → P in HFE2A. 1 PublicationCorresponds to variant rs74315327dbSNPEnsembl.1
Natural variantiVAR_019621168A → D in HFE2A. 1 PublicationCorresponds to variant rs782125244dbSNPEnsembl.1
Natural variantiVAR_019622170F → S in HFE2A. 1 Publication1
Natural variantiVAR_019623172D → E in HFE2A. 1 PublicationCorresponds to variant rs782708481dbSNPEnsembl.1
Natural variantiVAR_019624191W → C in HFE2A. 1 Publication1
Natural variantiVAR_019625205S → R in HFE2A. 1 Publication1
Natural variantiVAR_019626222I → N in HFE2A. 2 PublicationsCorresponds to variant rs74315325dbSNPEnsembl.1
Natural variantiVAR_019627250G → V in HFE2A. 1 Publication1
Natural variantiVAR_019628288R → W in HFE2A. 1 Publication1
Natural variantiVAR_053636310A → G.Corresponds to variant rs7540883dbSNPEnsembl.1
Natural variantiVAR_019629320G → V in HFE2A. 4 PublicationsCorresponds to variant rs74315323dbSNPEnsembl.1
Natural variantiVAR_019927321C → W in HFE2A. 1 PublicationCorresponds to variant rs121434374dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0113201 – 226Missing in isoform c. 1 PublicationAdd BLAST226
Alternative sequenceiVSP_0113191 – 113Missing in isoform b. 2 PublicationsAdd BLAST113

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY372521 mRNA. Translation: AAR22390.1.
AK092682 mRNA. Translation: BAC03944.1.
AK124273 mRNA. Translation: BAC85823.1.
AK092692 mRNA. Translation: BAC03947.1.
AK096905 mRNA. Translation: BAC04890.1.
DQ309445 Genomic DNA. Translation: ABC40718.1.
AL355505, AL138842 Genomic DNA. Translation: CAI22091.1.
AL138842, AL355505 Genomic DNA. Translation: CAI22349.1.
CH471244 Genomic DNA. Translation: EAW71408.1.
BC017926 mRNA. Translation: AAH17926.1.
BC085604 mRNA. Translation: AAH85604.1.
CCDSiCCDS72877.1. [Q6ZVN8-3]
CCDS72878.1. [Q6ZVN8-2]
CCDS72879.1. [Q6ZVN8-1]
RefSeqiNP_001303696.1. NM_001316767.1. [Q6ZVN8-3]
NP_660320.3. NM_145277.4. [Q6ZVN8-2]
NP_973733.1. NM_202004.3. [Q6ZVN8-3]
NP_998817.1. NM_213652.3. [Q6ZVN8-3]
NP_998818.1. NM_213653.3. [Q6ZVN8-1]
XP_005272989.1. XM_005272932.1. [Q6ZVN8-1]
UniGeneiHs.632436.

Genome annotation databases

EnsembliENST00000336751; ENSP00000337014; ENSG00000168509. [Q6ZVN8-1]
ENST00000357836; ENSP00000350495; ENSG00000168509. [Q6ZVN8-2]
ENST00000475797; ENSP00000425716; ENSG00000168509. [Q6ZVN8-3]
ENST00000497365; ENSP00000421820; ENSG00000168509. [Q6ZVN8-3]
ENST00000636675; ENSP00000490072; ENSG00000168509. [Q6ZVN8-3]
GeneIDi148738.
KEGGihsa:148738.
UCSCiuc001eni.3. human. [Q6ZVN8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY372521 mRNA. Translation: AAR22390.1.
AK092682 mRNA. Translation: BAC03944.1.
AK124273 mRNA. Translation: BAC85823.1.
AK092692 mRNA. Translation: BAC03947.1.
AK096905 mRNA. Translation: BAC04890.1.
DQ309445 Genomic DNA. Translation: ABC40718.1.
AL355505, AL138842 Genomic DNA. Translation: CAI22091.1.
AL138842, AL355505 Genomic DNA. Translation: CAI22349.1.
CH471244 Genomic DNA. Translation: EAW71408.1.
BC017926 mRNA. Translation: AAH17926.1.
BC085604 mRNA. Translation: AAH85604.1.
CCDSiCCDS72877.1. [Q6ZVN8-3]
CCDS72878.1. [Q6ZVN8-2]
CCDS72879.1. [Q6ZVN8-1]
RefSeqiNP_001303696.1. NM_001316767.1. [Q6ZVN8-3]
NP_660320.3. NM_145277.4. [Q6ZVN8-2]
NP_973733.1. NM_202004.3. [Q6ZVN8-3]
NP_998817.1. NM_213652.3. [Q6ZVN8-3]
NP_998818.1. NM_213653.3. [Q6ZVN8-1]
XP_005272989.1. XM_005272932.1. [Q6ZVN8-1]
UniGeneiHs.632436.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UI1X-ray2.35C/D35-145[»]
ProteinModelPortaliQ6ZVN8.
SMRiQ6ZVN8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61608N.
IntActiQ6ZVN8. 4 interactors.
STRINGi9606.ENSP00000337014.

PTM databases

iPTMnetiQ6ZVN8.
PhosphoSitePlusiQ6ZVN8.

Polymorphism and mutation databases

BioMutaiHFE2.
DMDMi51316254.

Proteomic databases

PaxDbiQ6ZVN8.
PeptideAtlasiQ6ZVN8.
PRIDEiQ6ZVN8.

Protocols and materials databases

DNASUi148738.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336751; ENSP00000337014; ENSG00000168509. [Q6ZVN8-1]
ENST00000357836; ENSP00000350495; ENSG00000168509. [Q6ZVN8-2]
ENST00000475797; ENSP00000425716; ENSG00000168509. [Q6ZVN8-3]
ENST00000497365; ENSP00000421820; ENSG00000168509. [Q6ZVN8-3]
ENST00000636675; ENSP00000490072; ENSG00000168509. [Q6ZVN8-3]
GeneIDi148738.
KEGGihsa:148738.
UCSCiuc001eni.3. human. [Q6ZVN8-1]

Organism-specific databases

CTDi148738.
DisGeNETi148738.
GeneCardsiHFE2.
GeneReviewsiHFE2.
HGNCiHGNC:4887. HFE2.
MalaCardsiHFE2.
MIMi602390. phenotype.
608374. gene.
neXtProtiNX_Q6ZVN8.
OpenTargetsiENSG00000168509.
Orphaneti79230. Hemochromatosis type 2.
PharmGKBiPA29264.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFAH. Eukaryota.
ENOG410ZT7E. LUCA.
GeneTreeiENSGT00390000008488.
HOGENOMiHOG000013072.
HOVERGENiHBG057627.
InParanoidiQ6ZVN8.
KOiK06847.
OMAiRFSRLHG.
OrthoDBiEOG091G0NF6.
PhylomeDBiQ6ZVN8.
TreeFamiTF329836.

Enzyme and pathway databases

ReactomeiR-HSA-373752. Netrin-1 signaling.

Miscellaneous databases

GeneWikiiHemojuvelin.
GenomeRNAii148738.
PROiQ6ZVN8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168509.
CleanExiHS_HFE2.
ExpressionAtlasiQ6ZVN8. baseline and differential.
GenevisibleiQ6ZVN8. HS.

Family and domain databases

InterProiIPR033606. Hemojuvelin.
IPR009496. RGM_C.
IPR010536. RGM_N.
[Graphical view]
PANTHERiPTHR31428:SF3. PTHR31428:SF3. 1 hit.
PfamiPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRGMC_HUMAN
AccessioniPrimary (citable) accession number: Q6ZVN8
Secondary accession number(s): B1ALI7
, Q2PQ63, Q6IMF6, Q8NAH2, Q8WVJ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 121 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 1
    Human chromosome 1: 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.