HFE

The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene. At least nine alternatively spliced variants have been described for this gene. Additional variants have been found but their full-length nature has not been determined. [provided by RefSeq]

Full Name

hemochromatosis

Function

Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.

Biological Process

BMP signaling pathway Source: BHF-UCL
Cellular iron ion homeostasis Source: UniProtKB
Cellular response to iron ion Source: BHF-UCL
Hormone biosynthetic process Source: Ensembl
Iron ion homeostasis Source: BHF-UCL
Iron ion import across plasma membrane Source: InterPro
Multicellular organismal iron ion homeostasis Source: Ensembl
Negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I Source: BHF-UCL
Negative regulation of CD8-positive, alpha-beta T cell activation Source: BHF-UCL
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
Negative regulation of receptor binding Source: BHF-UCL
Negative regulation of signaling receptor activity Source: BHF-UCL
Negative regulation of T cell antigen processing and presentation Source: InterPro
Negative regulation of T cell cytokine production Source: BHF-UCL
Negative regulation of ubiquitin-dependent protein catabolic process Source: BHF-UCL
Positive regulation of ferrous iron binding Source: BHF-UCL
Positive regulation of gene expression Source: BHF-UCL
Positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
Positive regulation of peptide hormone secretion Source: BHF-UCL
Positive regulation of protein binding Source: BHF-UCL
Positive regulation of receptor binding Source: BHF-UCL
Positive regulation of receptor-mediated endocytosis Source: BHF-UCL
Positive regulation of signaling receptor activity Source: BHF-UCL
Positive regulation of transferrin receptor binding Source: BHF-UCL
Protein-containing complex assembly Source: ProtInc
Regulation of iron ion transport Source: BHF-UCL
Regulation of protein localization to cell surface Source: BHF-UCL
Response to iron ion Source: BHF-UCL
Response to iron ion starvation Source: GO_Central

Cellular Location

Cell membrane

Involvement in disease

Hemochromatosis 1 (HFE1):
A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.
Variegate porphyria (VP):
Disease susceptibility is associated with variants affecting the gene represented in this entry. Iron overload due to HFE variants is a precipitating or exacerbating factor in variegate porphyria. A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Variegate porphyria is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease.
Microvascular complications of diabetes 7 (MVCD7):
Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.

Topology

Extracellular: 23-306
Helical: 307-330
Cytoplasmic: 331-348