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Hereditary hemochromatosis protein; HLA-H (HFE HLAH)

Function: - binds to transferrin receptor (TFR) & reduces its affinity for iron-loaded transferrin - binds TFR through the extracellular domain (pH-dependent) Structure: - belongs to the MHC class I family - contains 1 Ig-like C1-type (immunoglobulin-like) domain Compartment: - membrane; single-pass type 1 membrane protein Alternative splicing: - named isoforms=10 - at least some isoforms may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay Expression: - expressed within crypt enterocytes of duodenum - expressed in all tissues except brain Pathology: - defective protein in a) hereditary hemochromatosis b) porphyria cutanea tarda c) variegate porphyria d) susceptibility to diabetic nephropathy Laboratory: - HFE gene mutation

Interactions

molecular events

General

glycoprotein membrane protein

Properties

SIZE: entity length = 348 aa MW = 40 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-22} Alpha-1 {23-114} MOTIF: N-glycosylation site {N110} Alpha-2 {115-205} MOTIF: cysteine residue {C124} MODIFICATION: cysteine residue {C187} N-glycosylation site {N130} cysteine residue {C187} MODIFICATION: cysteine residue {C124} Alpha-3 {206-297} immunoglobulin superfamily domain {207-298} MOTIF: cysteine residue {C225} MODIFICATION: cysteine residue {C282} N-glycosylation site {N234} cysteine residue {C282} MODIFICATION: cysteine residue {C225} Connecting peptide {298-306} transmembrane domain {307-330}

Database Correlations

OMIM correlations UniProt Q30201 PFAM correlations Entrez Gene 3077 Kegg hsa:3077

References

  1. UniProt :accession Q30201
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/HFEID44099ch6p22.html
  3. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/HFE
  4. NIEHS-SNPs http://egp.gs.washington.edu/data/hfe/

Component-of

molecular complex