Ohgami Robert S, Campagna Dean R, McDonald Alice, Fleming Mark D
Department of Pathology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Blood. 2006 Aug 15;108(4):1388-94. doi: 10.1182/blood-2006-02-003681. Epub 2006 Apr 11.
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.
铁和铜对所有生物体来说都是必不可少的，它们在许多酶中作为辅因子发挥着关键作用。在真核生物中，这些元素的跨膜运输是一个高度受调控的过程，每种金属的单电子还原促进了这一过程。此前，我们鉴定出一种对红细胞铁稳态至关重要的哺乳动物铁还原酶Steap3。现在，通过同源性、表达和功能研究，我们对该蛋白家族的所有4个成员进行了表征，并证明其中3个成员，即Steap2、Steap3和Steap4，不仅是铁还原酶，还是铜还原酶，它们在体外能刺激细胞对铁和铜的摄取。最后，这些蛋白的组织表达模式和亚细胞定位表明，它们在体内是具有生理相关性的铜还原酶和铁还原酶。
