Family

Hereditary hemochromatosis protein (IPR031092)

Short name: HFE

Family relationships

None.

Description

Protein HFE is a member of the major histocompatibility complex class I-like family and a negative regulator of iron absorption. Mutations in the gene encoding HFE cause hereditary hemochromatosis (HH), a hereditary disease characterised by excessive intestinal absorption of dietary iron resulting in a pathological increase in total body iron stores [PMID: 8696333]. HFE interacts with transferrin receptor (TFR), a key protein involved in iron transport. An alteration in this regulatory mechanism could play a role in the pathogenesis of hereditary hemochromatosis [PMID: 9465039].

HFE, while structurally homologous to MHC I, is unable to bind peptides [PMID: 9546397]. However, several lines of evidence indicate that the role of HFE may extend toward a role in immunity. HFE may influence antigen presentation [PMID: 17339458, PMID: 15840699]. Furthermore, HFE appears to inhibit antigen-specific CD8(+) T-lymphocyte activation, probably due to altered intracellular processing of MHC I antigens [PMID: 24643698].

HFE gene variants correlate with body iron levels and have shown association with cancer risk, including childhood acute lymphoblastic leukemia [PMID: 25085015, PMID: 25700349].

GO terms

Biological Process

GO:0006879 cellular iron ion homeostasis
GO:0098711 iron ion import across plasma membrane
GO:0002626 negative regulation of T cell antigen processing and presentation

Molecular Function

GO:1990459 transferrin receptor binding

Cellular Component

GO:1990712 HFE-transferrin receptor complex

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PANTHER