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Reviewed, UniProtKB/Swiss-Prot Q6ZVN8 (RGMC_HUMAN)

Last modified November 4, 2008. Version 44. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Hemojuvelin
Alternative name(s):
    Hemochromatosis type 2 protein
    RGM domain family member C
Gene names
Name: HFE2
Synonyms: HJV, RGMC
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length426 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Involved in iron metabolism. May be a component of the signaling pathway which activates hepcidin (HAMP). May cooperate with hepcidin to restrict iron absorption in the gut. May act as a modulator of hepcidin expression, as deleterious mutations are associated with reduced hepcidin level. Could represent the cellular receptor for hepcidin.

Subcellular location

Cell membrane; Lipid-anchorGPI-anchorBy similarity.

Tissue specificity

Adult and fetal liver, heart, and skeletal muscle.

Involvement in disease

Defects in HFE2 are the cause of hemochromatosis type 2A (HFE2A) [MIM:602390]; also called juvenile hemochromatosis (JH). JH is an early-onset autosomal recessive disorder due to severe iron overload resulting in hypogonadotrophic hypogonadism, hepatic fibrosis or cirrhosis and cardiomyopathy, occurring typically before age of 30. It is the consequence of intestinal iron hyperabsorption associated with macrophages that do not load iron. Deleterious mutations of HFE2 reduced HAMP (hepcidin) levels despite iron overload, which normally induces HAMP expression.

Sequence similarities

Belongs to the repulsive guidance molecule (RGM) family.

Ontologies

Keywords

   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
   PTMGPI-anchor
Glycoprotein
Lipoprotein

Gene Ontology (GO)

   Cellular componentanchored to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform a (identifier: Q6ZVN8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform b (identifier: Q6ZVN8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-113: Missing.
Isoform c (identifier: Q6ZVN8-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Potential
Chain36 – 400365Hemojuvelin
PRO_0000030398
Propeptide401 – 42626Removed in mature form Potential
PRO_0000030399

Regions

Compositional bias64 – 7815Poly-Gly
Compositional bias127 – 1304Poly-Pro

Amino acid modifications

Lipidation4001GPI-anchor amidated aspartate Potential
Glycosylation1181N-linked (GlcNAc...) Potential
Glycosylation2131N-linked (GlcNAc...) Potential
Glycosylation3721N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 226226Missing in isoform c.
VSP_011320
Alternative sequence1 – 113113Missing in isoform b.
VSP_011319
Natural variant801C → R in HFE2A.
VAR_019617
Natural variant851S → P in HFE2A.
VAR_019618
Natural variant991G → R in HFE2A.
VAR_019619
Natural variant1011L → P in HFE2A.
VAR_019620
Natural variant1681A → D in HFE2A.
VAR_019621
Natural variant1701F → S in HFE2A.
VAR_019622
Natural variant1721D → E in HFE2A.
VAR_019623
Natural variant1911W → C in HFE2A.
VAR_019624
Natural variant2051S → R in HFE2A.
VAR_019625
Natural variant2221I → N in HFE2A.
VAR_019626
Natural variant2501G → V in HFE2A.
VAR_019627
Natural variant2881R → W in HFE2A.
VAR_019628
Natural variant3201G → V in HFE2A.
VAR_019629
Natural variant3211C → W in HFE2A.
VAR_019927

Experimental info

Sequence conflict691G → GG in ABC40718. Ref.3
Sequence conflict2991K → E in BAC03944. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform a [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 031C835F9B6DC06C

FASTA42645,080
        10         20         30         40         50         60 
MGEPGQSPSP RSSHGSPPTL STLTLLLLLC GHAHSQCKIL RCNAEYVSST LSLRGGGSSG 

        70         80         90        100        110        120 
ALRGGGGGGR GGGVGSGGLC RALRSYALCT RRTARTCRGD LAFHSAVHGI EDLMIQHNCS 

       130        140        150        160        170        180 
RQGPTAPPPP RGPALPGAGS GLPAPDPCDY EGRFSRLHGR PPGFLHCASF GDPHVRSFHH 

       190        200        210        220        230        240 
HFHTCRVQGA WPLLDNDFLF VQATSSPMAL GANATATRKL TIIFKNMQEC IDQKVYQAEV 

       250        260        270        280        290        300 
DNLPVAFEDG SINGGDRPGG SSLSIQTANP GNHVEIQAAY IGTTIIIRQT AGQLSFSIKV 

       310        320        330        340        350        360 
AEDVAMAFSA EQDLQLCVGG CPPSQRLSRS ERNRRGAITI DTARRLCKEG LPVEDAYFHS 

       370        380        390        400        410        420 
CVFDVLISGD PNFTVAAQAA LEDARAFLPD LEKLHLFPSD AGVPLSSATL LAPLLSGLFV 


LWLCIQ 

« Hide

Isoform b [UniParc].

Checksum: 0B056ED5D92B26E6
Show »

31333,679
Isoform c [UniParc].

Checksum: 7A7F39D3AD7F8CC5
Show »

20021,463

References

« Hide 'large scale' references
[1]"Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis."
Papanikolaou G., Samuels M.E., Ludwig E.H., MacDonald M.L.E., Franchini P.L., Dube M.-P., Andres L., MacFarlane J., Sakellaropoulos N., Politou M., Nemeth E., Thompson J., Risler J.K., Zaborowska C., Babakaiff R., Radomski C.C., Pape T.D., Davidas O. expand/collapse author list , Christakis J., Brissot P., Lockitch G., Ganz T., Hayden M.R., Goldberg Y.P.
Nat. Genet. 36:77-82(2004) [PubMed: 14647275] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, VARIANTS HFE2A ASN-222 AND VAL-320.
Tissue: Liver.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
Tissue: Liver and Skeletal muscle.
[3]"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."
Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS B AND C).
Tissue: PNS and Skeletal muscle.
[5]"Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis."
Lanzara C., Roetto A., Daraio F., Rivard S., Ficarella R., Simard H., Cox T.M., Cazzola M., Piperno A., Gimenez-Roqueplo A.P., Grammatico P., Volinia S., Gasparini P., Camaschella C.
Blood 103:4317-4321(2004) [PubMed: 14982873] [Abstract]
Cited for: VARIANTS HFE2A PRO-85; ARG-99; ASP-168; SER-170; GLU-172; CYS-191; ARG-205; VAL-250; TRP-288 AND VAL-320.
[6]"Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin."
Lee P.L., Beutler E., Rao S.V., Barton J.C.
Blood 103:4669-4671(2004) [PubMed: 14982867] [Abstract]
Cited for: VARIANTS HFE2A ARG-80; PRO-101; ASN-222 AND VAL-320.
[7]"Hemojuvelin (HJV) mutations in persons of European, African-American and Asian ancestry with adult onset haemochromatosis."
Lee P.L., Barton J.C., Brandhagen D., Beutler E.
Br. J. Haematol. 127:224-229(2004) [PubMed: 15461631] [Abstract]
Cited for: VARIANTS HFE2A VAL-320 AND TRP-321.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

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.
BC017926 mRNA. Translation: AAH17926.1.
BC085604 mRNA. Translation: AAH85604.1.
RefSeqNP_660320.3.
NP_973733.1.
NP_998817.1.
NP_998818.1.
UniGeneHs.632436

3D structure databases

ModBaseSearch...

Polymorphism databases

NIEHS-SNPsSearch...

Genome annotation databases

EnsemblENSG00000168509. Homo sapiens. [Contig view]
GeneID148738.
KEGGhsa:148738.

Organism-specific databases

H-InvDBHIX0000970.
HGNCHGNC:4887. HFE2.
HPAHPA014472.
MIM602390. phenotype.
608374. gene.
PharmGKBPA29264.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ6ZVN8.
HOVERGENQ6ZVN8.

Gene expression databases

ArrayExpressQ6ZVN8.
CleanExHS_HFE2.
GermOnlineENSG00000168509. Homo sapiens.

Family and domain databases

InterProIPR009496. RGM_C.
IPR010536. RGM_N.
[Graphical view]
PfamPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio85978.
SOURCESearch...

Entry information

Entry nameRGMC_HUMAN
AccessionPrimary (citable) accession number: Q6ZVN8
Secondary accession number(s): Q2PQ63 expand/collapse secondary AC list , Q6IMF6, Q8NAH2, Q8WVJ5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: November 4, 2008
This is version 44 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents