Hemojuvelin / HFE2

Hemojuvelin, also known as HFE2, is a membrane-bound and soluble protein which belongs to the repulsive guidance molecule (RGM) family. It is known that RGMs function through Neogenin, a homologue of the Netrin receptor deleted in colon cancer. In mammals, RGM family consists of three glycoproteins which have discrete expression patterns and functions (RGM-A, RGM-B, and RGM-C). Hemojuvelin is expressed in adult and fetal liver, heart, and skeletal muscle. Hemojuvelin acts as a bone morphogenetic protein (BMP) coreceptor. Enhancement of BMP signaling regulates hepcidin (HAMP) expression and iron metabolism. It plays a key role in iron metabolism. Hemojuvelin represents the cellular receptor for hepcidin. It may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression. Defects in hemojuvelin are the cause of hemochromatosis type 2A, also known as juvenile hemochromatosis (JH).

Hemojuvelin / HFE2 Related Areas

Signal Transduction>>Transcription Factor & Regulator>>Hemojuvelin/HFE2

Hemojuvelin / HFE2 Alternative Names

HFE2A, HJV, JH, MGC23953, RGMC, RGM domain family member C, haemojuvelin, hemochromatosis type 2 protein, hemojuvelin, repulsive guidance molecule c [Homo sapiens]

2310035L15Rik, 5230400G09Rik, AI414844, AI789733, DL-M, HJV, Rgmc, hemojuvelin, RGM domain family member C, hemochromatosis type 2 protein homolog, hemojuvelin, repulsive guidance molecule C [Mus musculus]

Summaries for Hemojuvelin / HFE2

Entrez Gene summary for Hemojuvelin / HFE2:

The product of this gene is involved in iron metabolism. It may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression. It could also represent the cellular receptor for hepcidin. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Defects in this gene are the cause of hemochromatosis type 2A, 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.

OMIM - description for Hemojuvelin / HFE2:

By a positional cloning strategy, Papanikolaou et al. (2004) identified the HJV gene within the region associated with juvenile hemochromatosis on chromosome 1q21 (HFE2A; 602390). By Northern blot analysis of human tissues, Papanikolaou et al. (2004) found that hemojuvelin transcript expression was restricted to liver, heart, and skeletal muscle, similar to that of hepcidin (HAMP; 606464), a key protein implicated in iron metabolism that is mutant in juvenile hemochromatosis showing linkage to 19q. A primary 2.2-kb transcript was expressed in these tissues. Hemojuvelin is transcribed from a gene of 4,265 bp into a full-length transcript with 5 spliced isoforms. The putative full-length protein from the longest transcript is 426 amino acids. Hemojuvelin contains multiple protein motifs consistent with a function as a membrane-bound receptor or secreted polypeptide hormone.

Wikipedia summary for Hemojuvelin / HFE2:

Hemojuvelin (HJV/RGMc/HFE2) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis in humans, a severe form of hemochromatosis. In humans, the hemojuvelin protein is encoded by the HFE2 gene.HJV is also called RGMc, a member of a three gene family (in vertebrates) called the repulsive guidance molecules. Both RGMa and RGMb are found in the nervous system, while RGMc is found in skeletal muscle and the liver

Human Hemojuvelin / HFE2 Protein General Information

 

• Protein names: Recommended name: Hemojuvelin
• Sequence length: 426 AA.
• Domain: Signal
• Subunit structure: Interacts with BMP2 and BMP4 By similarity. Interacts with BMPR1B.
• Subcellular location: Cell membrane; Lipid-anchor › GPI-anchor
• 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 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

General information above from UniProt

Function for Hemojuvelin / HFE2 Protein

UniProtKB:

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.

Genatlas:

• glycosylphosphatidylinositol-linked protein potential modulator of hepcidin (HAMP) expression, playing a key role in dietary iron sensing
• Hemojuvelin / HFE2 Protein may cooperate with hepcidin to restrict iron absorption in the gut
• Hemojuvelin / HFE2 Protein interactes with NEO1 to mediate the induction of hepcidin expression
• binding BMP6 and increasing HAMP expression presumably by acting as a BMP co-receptor
• expression in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling
• Hemojuvelin / HFE2 Protein may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression
• Hemojuvelin / HFE2 Protein could also represent the cellular receptor for hepcidin
• Hemojuvelin / HFE2 Protein acts as a bone morphogenetic protein coreceptor to activate hepcidin expression through a SMAD signaling pathway in hepatocytes
• Hemojuvelin / HFE2 Protein is primarily important in the liver;

Homology for human Hemojuvelin / HFE2

• ortholog to murine Hfe2
• ortholog to rattus Rgmc_predicted

Phenotype Information for Hemojuvelin / HFE2

• Gene/Locus: HJV, HFE2A
• Phenotype: Hemochromatosis, type 2A

Phenotype Information for Hemojuvelin / HFE2 from OMIM (Online Mendelian Inheritance in Man)