STEAP3
Encyclopedia
Metalloreductase STEAP3 is an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that in humans is encoded by the STEAP3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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STEAP3 is a metalloreductase, capable of coverting iron from an insoluble ferric
Ferric
Ferric refers to iron-containing materials or compounds. In chemistry the term is reserved for iron with an oxidation number of +3, also denoted iron or Fe3+. On the other hand, ferrous refers to iron with oxidation number of +2, denoted iron or Fe2+...

 (Fe3+) to a soluble ferrous
Ferrous
Ferrous , in chemistry, indicates a divalent iron compound , as opposed to ferric, which indicates a trivalent iron compound ....

 (Fe2+) form.

The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80% of the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism for iron uptake in which iron loaded transferrin (Tf) binds to the transferrin receptor (TfR) at the cell surface. The Tf:TfR complex then enters the endosome via receptor-mediated endocytosis. Upon endosomal acidification, iron is released from Tf, reduced to Fe2+ by Steap3, and transported across the endosomal membrane by divalent metal ion transporter 1. Steap3 is composed of an N-terminal cytosolic oxidoreductase domain and a C-terminal heme-containing transmembrane domain. The NADPH/flavin binding domain of Steap3 differs significantly from those in other eukaryotic reductases. Steap3 shows remarkable, although limited homology to FNO, an archaeal oxidoreductase. We have determined the crystal structure of the human-Steap3 oxidoreductase domain in the absence and presence of NADPH (PDB-ID 2vns and 2vq3). The structure of the oxidoreductase domain reveals an unexpected dimer interface and substrate binding sites that are well positioned to direct electron transfer from the cytosol to a transmembrane heme moiety.

Interactions

STEAP3 has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with BNIP3L
BNIP3L
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like is a protein that in humans is encoded by the BNIP3L gene.-Further reading:...

 and PKMYT1
PKMYT1
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase is an enzyme that in humans is encoded by the PKMYT1 gene.-Interactions:PKMYT1 has been shown to interact with PIN1 and STEAP3.-Further reading:...

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