The Steap proteins are metalloreductases.
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.
Ohgami
Robert S
RS
Department of Pathology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Campagna
Dean R
DR
McDonald
Alice
A
Fleming
Mark D
MD
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003067:Coenzymes / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D000951:Antigens, Neoplasm; D003067:Coenzymes; D012333:RNA, Messenger; C486624:Steap protein, mouse; D003300:Copper; D007501:Iron; D010088:Oxidoreductases