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Protein

Hemojuvelin

Gene

HJV

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • signaling receptor binding Source: BHF-UCL
  • transferrin receptor binding Source: BHF-UCL

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-373752 Netrin-1 signaling

Names & Taxonomyi

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

Organism-specific databases

EuPathDBiHostDB:ENSG00000168509.18
HGNCiHGNC:4887 HJV
MIMi608374 gene
neXtProtiNX_Q6ZVN8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs28940586EnsemblClinVar.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 dbSNP:rs74315327EnsemblClinVar.1
Natural variantiVAR_019621168A → D in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs782125244Ensembl.1
Natural variantiVAR_019622170F → S in HFE2A. 1 Publication1
Natural variantiVAR_019623172D → E in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs782708481Ensembl.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 dbSNP:rs74315325EnsemblClinVar.1
Natural variantiVAR_019627250G → V in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs863224819EnsemblClinVar.1
Natural variantiVAR_019628288R → W in HFE2A. 1 Publication1
Natural variantiVAR_019629320G → V in HFE2A. 4 PublicationsCorresponds to variant dbSNP:rs74315323EnsemblClinVar.1
Natural variantiVAR_019927321C → W in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs121434374Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi148738
GeneReviewsiHFE2
MalaCardsiHJV
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...) asparagineSequence analysis1
Disulfide bondi148 ↔ 230By similarity
Disulfide bondi167 ↔ 317By similarity
Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi372N-linked (GlcNAc...) asparagineSequence 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 HJV 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
ProteomicsDBi68432
68433 [Q6ZVN8-2]
68434 [Q6ZVN8-3]

PTM databases

iPTMnetiQ6ZVN8
PhosphoSitePlusiQ6ZVN8

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000168509 Expressed in 92 organ(s), highest expression level in quadriceps femoris
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

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-61608N
IntActiQ6ZVN8, 5 interactors
STRINGi9606.ENSP00000337014

Structurei

Secondary structure

1426
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiAPDPCDY
OrthoDBiEOG091G0NF6
PhylomeDBiQ6ZVN8
TreeFamiTF329836

Family and domain databases

Gene3Di3.40.1000.10, 1 hit
InterProiView protein in InterPro
IPR033606 Hemojuvelin
IPR016123 Mog1/PsbP_a/b/a-sand
IPR009496 RGM_C
IPR010536 RGM_N
PANTHERiPTHR31428:SF3 PTHR31428:SF3, 1 hit
PfamiView protein in Pfam
PF06534 RGM_C, 1 hit
PF06535 RGM_N, 1 hit

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W6J7F8W6J7_HUMAN
Hemojuvelin
HJV
93Annotation score:
A0A0U1RR55A0A0U1RR55_HUMAN
Hemojuvelin
HJV
70Annotation score:

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 dbSNP:rs28940586EnsemblClinVar.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 dbSNP:rs74315327EnsemblClinVar.1
Natural variantiVAR_019621168A → D in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs782125244Ensembl.1
Natural variantiVAR_019622170F → S in HFE2A. 1 Publication1
Natural variantiVAR_019623172D → E in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs782708481Ensembl.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 dbSNP:rs74315325EnsemblClinVar.1
Natural variantiVAR_019627250G → V in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs863224819EnsemblClinVar.1
Natural variantiVAR_019628288R → W in HFE2A. 1 Publication1
Natural variantiVAR_053636310A → G. Corresponds to variant dbSNP:rs7540883EnsemblClinVar.1
Natural variantiVAR_019629320G → V in HFE2A. 4 PublicationsCorresponds to variant dbSNP:rs74315323EnsemblClinVar.1
Natural variantiVAR_019927321C → W in HFE2A. 1 PublicationCorresponds to variant dbSNP:rs121434374Ensembl.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

Similar proteinsi

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, 5 interactors
STRINGi9606.ENSP00000337014

PTM databases

iPTMnetiQ6ZVN8
PhosphoSitePlusiQ6ZVN8

Polymorphism and mutation databases

BioMutaiHFE2
DMDMi51316254

Proteomic databases

PaxDbiQ6ZVN8
PeptideAtlasiQ6ZVN8
PRIDEiQ6ZVN8
ProteomicsDBi68432
68433 [Q6ZVN8-2]
68434 [Q6ZVN8-3]

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
EuPathDBiHostDB:ENSG00000168509.18
GeneCardsiHJV
GeneReviewsiHFE2
HGNCiHGNC:4887 HJV
MalaCardsiHJV
MIMi602390 phenotype
608374 gene
neXtProtiNX_Q6ZVN8
OpenTargetsiENSG00000168509
Orphaneti79230 Hemochromatosis type 2
PharmGKBiPA29264
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-373752 Netrin-1 signaling

Miscellaneous databases

GeneWikiiHemojuvelin
GenomeRNAii148738
PROiPR:Q6ZVN8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168509 Expressed in 92 organ(s), highest expression level in quadriceps femoris
CleanExiHS_HFE2
ExpressionAtlasiQ6ZVN8 baseline and differential
GenevisibleiQ6ZVN8 HS

Family and domain databases

Gene3Di3.40.1000.10, 1 hit
InterProiView protein in InterPro
IPR033606 Hemojuvelin
IPR016123 Mog1/PsbP_a/b/a-sand
IPR009496 RGM_C
IPR010536 RGM_N
PANTHERiPTHR31428:SF3 PTHR31428:SF3, 1 hit
PfamiView protein in Pfam
PF06534 RGM_C, 1 hit
PF06535 RGM_N, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRGMC_HUMAN
AccessioniPrimary (citable) accession number: Q6ZVN8
Secondary accession number(s): B1ALI7
, Q2PQ63, Q6IMF6, Q8NAH2, Q8WVJ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: November 7, 2018
This is version 136 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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