Hemojuvelin precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Hemojuvelin
Alternative name(s):
    Hemochromatosis type 2 protein
    RGM domain family member C

Gene names

Name:	HFE2
Synonyms:	HJV, RGMC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	426 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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-anchor › GPI-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.

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Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Signal
PTM	GPI-anchor Glycoprotein Lipoprotein
Gene Ontology (GO)
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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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.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 35

35

Potential

Chain

36 – 400

365

Hemojuvelin

PRO_0000030398

Propeptide

401 – 426

26

Removed in mature form Potential

PRO_0000030399

Regions

Compositional bias

64 – 78

15

Poly-Gly

Compositional bias

127 – 130

4

Poly-Pro

Amino acid modifications

Lipidation

400

1

GPI-anchor amidated aspartate Potential

Glycosylation

118

1

N-linked (GlcNAc...) Potential

Glycosylation

213

1

N-linked (GlcNAc...) Potential

Glycosylation

372

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 226

226

Missing in isoform c.

VSP_011320

Alternative sequence

1 – 113

113

Missing in isoform b.

VSP_011319

Natural variant

80

1

C → R in HFE2A.

VAR_019617

Natural variant

85

1

S → P in HFE2A.

VAR_019618

Natural variant

99

1

G → R in HFE2A.

VAR_019619

Natural variant

101

1

L → P in HFE2A.

VAR_019620

Natural variant

168

1

A → D in HFE2A.

VAR_019621

Natural variant

170

1

F → S in HFE2A.

VAR_019622

Natural variant

172

1

D → E in HFE2A.

VAR_019623

Natural variant

191

1

W → C in HFE2A.

VAR_019624

Natural variant

205

1

S → R in HFE2A.

VAR_019625

Natural variant

222

1

I → N in HFE2A.

VAR_019626

Natural variant

250

1

G → V in HFE2A.

VAR_019627

Natural variant

288

1

R → W in HFE2A.

VAR_019628

Natural variant

320

1

G → V in HFE2A.

VAR_019629

Natural variant

321

1

C → W in HFE2A.

VAR_019927

Experimental info

Sequence conflict

69

1

G → GG in ABC40718. Ref.3

Sequence conflict

299

1

K → E in BAC03944. Ref.2

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Sequences

Sequence		Length	Mass (Da)
Isoform a [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 031C835F9B6DC06C Show »	FASTA	426	45,080
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 »		313	33,679
10 20 30 40 50 60 MIQHNCSRQG PTAPPPPRGP ALPGAGSGLP APDPCDYEGR FSRLHGRPPG FLHCASFGDP 70 80 90 100 110 120 HVRSFHHHFH TCRVQGAWPL LDNDFLFVQA TSSPMALGAN ATATRKLTII FKNMQECIDQ 130 140 150 160 170 180 KVYQAEVDNL PVAFEDGSIN GGDRPGGSSL SIQTANPGNH VEIQAAYIGT TIIIRQTAGQ 190 200 210 220 230 240 LSFSIKVAED VAMAFSAEQD LQLCVGGCPP SQRLSRSERN RRGAITIDTA RRLCKEGLPV 250 260 270 280 290 300 EDAYFHSCVF DVLISGDPNF TVAAQAALED ARAFLPDLEK LHLFPSDAGV PLSSATLLAP 310 LLSGLFVLWL CIQ « Hide
Isoform c [UniParc]. Checksum: 7A7F39D3AD7F8CC5 Show »		200	21,463
10 20 30 40 50 60 MQECIDQKVY QAEVDNLPVA FEDGSINGGD RPGGSSLSIQ TANPGNHVEI QAAYIGTTII 70 80 90 100 110 120 IRQTAGQLSF SIKVAEDVAM AFSAEQDLQL CVGGCPPSQR LSRSERNRRG AITIDTARRL 130 140 150 160 170 180 CKEGLPVEDA YFHSCVFDVL ISGDPNFTVA AQAALEDARA FLPDLEKLHL FPSDAGVPLS 190 200 SATLLAPLLS GLFVLWLCIQ « Hide

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References

	« Hide 'large scale' referencesShow '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. 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. 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.

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Web resources

GeneReviews

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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.
RefSeq	NP_660320.3. NP_973733.1. NP_998817.1. NP_998818.1.
UniGene	Hs.632436
3D structure databases
ModBase	Search...
Polymorphism databases
NIEHS-SNPs	Search...
Genome annotation databases
Ensembl	ENSG00000168509. Homo sapiens. [Contig view]
GeneID	148738.
KEGG	hsa:148738.
Organism-specific databases
H-InvDB	HIX0000970.
HGNC	HGNC:4887. HFE2.
HPA	HPA014472.
MIM	602390. phenotype. 608374. gene.
PharmGKB	PA29264.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q6ZVN8.
HOVERGEN	Q6ZVN8.
Gene expression databases
ArrayExpress	Q6ZVN8.
CleanEx	HS_HFE2.
GermOnline	ENSG00000168509. Homo sapiens.
Family and domain databases
InterPro	IPR009496. RGM_C. IPR010536. RGM_N. [Graphical view]
Pfam	PF06534. RGM_C. 1 hit. PF06535. RGM_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	85978.
SOURCE	Search...

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Entry information

Entry name

RGMC_HUMAN

Accession

Primary (citable) accession number: Q6ZVN8
Secondary accession number(s): Q2PQ63

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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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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

Keywords

Gene Ontology (GO)

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Polymorphism databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents