HFE

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HFE is named after High Fe (iron). The gene products known function is to regulate iron absorption by interacting with the transferrin receptor (TfR). Both HFE and transferrin (Tf) compete with each other for binding to the receptor (TfR)[1]. Tf binds to iron in the form of diferric transferrin (Fe-Tf) and binds to free TfR which takes the iron into the cell by an endocytosis cycle[2]. When the normal function of HFE is disrupted by mutation the result can be HFE hereditary hemochromatosis or iron overload.

DNA Sequence

HFE is located on chromosome 6 in humans.

RNA Sequence

There are several alternatively spliced variants of HFE.

Protein Sequence

The protein has a signal sequence and transmembrane domain. It forms a tertiary complex with beta2-microglobulin (beta2M) and TfR. HFE has sequence and structural similarity to MHC class I-type proteins.

NCBI Protein[1]

>gi|4504377|ref|NP_000401.1| hereditary hemochromatosis protein isoform 1 precursor [Homo sapiens]
MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEP
RTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGY
DGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLV
KVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRY
TCQVEHPGLDQPLIVIWEPSPSGTLVIGVISGIAVFVVILFIGILFIILRKRQGSRGAMGHYVLAERE

NCBI Structure[2]

HFE (magenta) tertiary complex with beta2M (blue)[3]

HFE-beta2M-2.png

HFE (magenta and green) tertiary complex with beta2M (blue and gray) and TfR (yellow and brown)[4]

HFE-beta2M-TfR-2.png

Plot in Protter[3] with UniProt accession: Q30201

HFE protter.png

  1. Lebrón, J. A., West Jr, A. P., & Bjorkman, P. J. (1999). The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor. Journal of molecular biology, 294(1), 239-245.
  2. Qian, Z. M., Li, H., Sun, H., & Ho, K. (2002). Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacological reviews, 54(4), 561-587.
  3. Lebron, J. A., Bennett, M. J., Vaughn, D. E., Chirino, A. J., Snow, P. M., Mintier, G. A., ... & Bjorkman, P. J. (1998). Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell, 93(1), 111-123.
  4. Bennett, M. J., Lebrón, J. A., & Bjorkman, P. J. (2000). Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature, 403(6765), 46-53.