Alternative titles; symbols
HGNC Approved Gene Symbol: CYBRD1
Cytogenetic location: 2q31.1 Genomic coordinates (GRCh38) : 2:171,522,233-171,558,129 (from NCBI)
The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. McKie et al. (2001) isolated a cDNA, which they called Dcytb for 'duodenal cytochrome b,' that encodes a putative plasma membrane di-heme protein in mouse duodenal mucosa. By searching EST databases, the authors also found a fully sequenced cDNA clone from a human small intestine library containing the full-length human DCYTB cDNA (GenBank AK027115). DCYTB encodes a protein with 6 predicted transmembrane domains and 4 conserved histidine residues which are proposed heme ligands. DCYTB shares 45 to 50% similarity with the cytochrome b561 (600019) family of plasma membrane reductases, is highly expressed in the brush-border membrane of duodenal enterocytes, and induces ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of DCYTB mRNA and protein were regulated by changes in physiologic modulators of iron absorption, including chronic anemia, iron deficiency, and hypoxia. Three major transcripts of 1, 4, and greater than 5 kb were detectable by Northern blot analysis, indicative of alternative splicing or the presence of unprocessed pre-mRNA species. DCYTB appears to lack any conventional NADH-, NADPH-, or flavin-binding motifs that would allow these cofactors to act as intracellular electron donors. Cytochrome b561 receives an electron from ascorbate and does not appear to require other components. McKie et al. (2001) speculated that DCYTB may also use ascorbate or, like gp91-phox (300481), associate with several other proteins to form an active complex.
Zoller et al. (2003) studied the mRNA and protein expression and activity of DCYTB in duodenal biopsies of patients with iron deficiency anemia, hereditary hemochromatosis (235200), and controls. They found that DCYTB activity in iron deficiency is stimulated via enhanced protein expression, whereas in hemochromatosis due to mutations in the HFE gene (613609) it is upregulated posttranslationally. Hemochromatosis patients with no mutations in HFE did not have increased DCYTB activity. Zoller et al. (2003) concluded that there are different kinetics of intestinal iron uptake between iron deficiency and hemochromatosis due to mutations in HFE, and that duodenal iron accumulation in hereditary hemochromatosis due to mutations in HFE and hereditary hemochromatosis due to mutations in other genes is pathophysiologically different.
The International Radiation Hybrid Mapping Consortium mapped the CYBRD1 gene to chromosome 2 (RH46529).
McKie, A. T., Barrow, D., Latunde-Dada, G. O., Rolfs, A., Sager, G., Mudaly, E., Mudaly, M., Richardson, C., Barlow, D., Bomford, A., Peters, T. J., Raja, K. B., Shirali, S., Hediger, M. A., Farzaneh, F., Simpson, R. J. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291: 1755-1759, 2001. [PubMed: 11230685] [Full Text: https://doi.org/10.1126/science.1057206]
Zoller, H., Theurl, I., Koch, R. O., McKie, A. T., Vogel, W., Weiss, G. Duodenal cytochrome b and hephaestin expression in patients with iron deficiency and hemochromatosis. Gastroenterology 125: 746-754, 2003. [PubMed: 12949720] [Full Text: https://doi.org/10.1016/s0016-5085(03)01063-1]