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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1388-1394.
Prepublished online as a Blood First Edition Paper on April 11, 2006; DOI 10.1182/blood-2006-02-003681.
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RED CELLS
The Steap proteins are metalloreductases
Robert S. Ohgami,
Dean R. Campagna,
Alice McDonald, and
Mark D. Fleming
From the Department of Pathology, Children's Hospital and Harvard Medical School, Boston, MA; and Millennium Pharmaceuticals, Cambridge, MA.
Iron and copper are essential for all organisms, assuming critical roles as cofactors in many enzymes. In eukaryotes, the transmembrane transport of these elements is a highly regulated process facilitated by the single electron reduction of each metal. Previously, we identified a mammalian ferrireductase, Steap3, critical for erythroid iron homeostasis. Now, through homology, expression, and functional studies, we characterize all 4 members of this protein family and demonstrate that 3 of them, Steap2, Steap3, and Steap4, are not only ferrireductases but also cupric reductases that stimulate cellular uptake of both iron and copper in vitro. Finally, the pattern of tissue expression and subcellular localization of these proteins suggest they are physiologically relevant cupric reductases and ferrireductases in vivo.

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