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Q6ZVN8 (RGMC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 75. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
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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 lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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

Member of the repulsive guidance molecule (RGM) family. Involved in iron metabolism. Acts as a bone morphogenetic protein (BMP) coreceptor By similarity. Enhancement of BMP signaling regulates hepcidin (HAMP) expression and iron metabolism By similarity. May cooperate with hepcidin to restrict iron absorption in the gut. Could represent the cellular receptor for hepcidin.

Subunit structure

Interacts with BMP2 and BMP4 By similarity. Interacts with BMPR1B. Ref.7

Subcellular location

Cell membrane; Lipid-anchor › GPI-anchor By similarity.

Tissue specificity

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

Involvement in disease

Defects in HFE2 are the cause of hemochromatosis type 2A (HFE2A) [MIM:602390]; also known as juvenile hemochromatosis (JH). HFE2A 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. Ref.1 Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the repulsive guidance molecule (RGM) family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainSignal
   PTMGPI-anchor
Glycoprotein
Lipoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processaxon guidance

Traceable author statement. Source: Reactome

   Cellular componentanchored to 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. Ref.9
Corresponds to variant rs28940586 [ dbSNP | Ensembl ].
VAR_019617
Natural variant851S → P in HFE2A. Ref.8
VAR_019618
Natural variant991G → R in HFE2A. Ref.8
VAR_019619
Natural variant1011L → P in HFE2A. Ref.9
VAR_019620
Natural variant1681A → D in HFE2A. Ref.8
VAR_019621
Natural variant1701F → S in HFE2A. Ref.8
VAR_019622
Natural variant1721D → E in HFE2A. Ref.8
VAR_019623
Natural variant1911W → C in HFE2A. Ref.8
VAR_019624
Natural variant2051S → R in HFE2A. Ref.8
VAR_019625
Natural variant2221I → N in HFE2A. Ref.1 Ref.9
VAR_019626
Natural variant2501G → V in HFE2A. Ref.8
VAR_019627
Natural variant2881R → W in HFE2A. Ref.8
VAR_019628
Natural variant3101A → G.
Corresponds to variant rs7540883 [ dbSNP | Ensembl ].
VAR_053636
Natural variant3201G → V in HFE2A. Ref.1 Ref.8 Ref.9 Ref.10
VAR_019629
Natural variant3211C → W in HFE2A. Ref.10
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 »

FASTA31333,679
Isoform c [UniParc].

Checksum: 7A7F39D3AD7F8CC5
Show »

FASTA20021,463

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 program
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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.
[7]"Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression."
Babitt J.L., Huang F.W., Wrighting D.M., Xia Y., Sidis Y., Samad T.A., Campagna J.A., Chung R.T., Schneyer A.L., Woolf C.J., Andrews N.C., Lin H.Y.
Nat. Genet. 38:531-539(2006) [PubMed: 16604073] [Abstract]
Cited for: INTERACTION WITH BMPR1B.
[8]"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.
[9]"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.
[10]"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

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00329576.
IPI00400863.
IPI00419814.
RefSeqNP_660320.3. NM_145277.4.
NP_973733.1. NM_202004.3.
NP_998817.1. NM_213652.3.
NP_998818.1. NM_213653.3.
UniGeneHs.632436.

3D structure databases

ProteinModelPortalQ6ZVN8.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ6ZVN8.

PTM databases

PhosphoSiteQ6ZVN8.

Polymorphism databases

DMDM51316254.

Proteomic databases

PRIDEQ6ZVN8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336751; ENSP00000337014; ENSG00000168509.
ENST00000393075; ENSP00000376791; ENSG00000168509.
GeneID148738.
KEGGhsa:148738.
UCSCuc001eni.2. human.
uc001enj.2. human.

Organism-specific databases

CTD148738.
GeneCardsGC01P145413.
H-InvDBHIX0000970.
HGNCHGNC:4887. HFE2.
HPAHPA014472.
MIM602390. phenotype.
608374. gene.
neXtProtNX_Q6ZVN8.
Orphanet79230. Hemochromatosis type 2.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG16430.
GeneTreeENSGT00390000008488.
HOGENOMHBG505677.
HOVERGENHBG057627.
InParanoidQ6ZVN8.
OMAPPGFLHC.
PhylomeDBQ6ZVN8.

Enzyme and pathway databases

Pathway_Interaction_DBbmppathway. BMP receptor signaling.
ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressQ6ZVN8.
BgeeQ6ZVN8.
CleanExHS_HFE2.
GenevestigatorQ6ZVN8.
GermOnlineENSG00000168509. Homo sapiens.

Family and domain databases

InterProIPR009496. RGM_C.
IPR010536. RGM_N.
[Graphical view]
KOK06847.
PfamPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio85978.
SOURCESearch...

Entry information

Entry nameRGMC_HUMAN
AccessionPrimary (citable) accession number: Q6ZVN8
Secondary accession number(s): B1ALI7 expand/collapse secondary AC list , Q2PQ63, Q6IMF6, Q8NAH2, Q8WVJ5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: January 25, 2012
This is version 75 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

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

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents