5.B.6.1.4
The epithelial plasma membrane antigen of the prostate (STEAP; STEAP1; DIS3) (Yang et al. 2001). It is a metalloreductase that can reduce both Fe³⁺ to Fe²⁺ and Cu²⁺ to Cu¹⁺ using NAD⁺ as the electron acceptor (Oosterheert and Gros 2020). However, STEAP1 (in contrast to STREAP2-4) lacks an intracellular NADPH-binding domain. Oosterheert and Gros 2020 presented a ~3.0 Å cryo-EM structure of trimeric human STEAP1. The structure shows that it adopts a reductase-like conformation and interacts with the Fabs through its extracellular helices. STEAP1 promotes iron(III) reduction when fused to the intracellular NADPH-binding domain of its family member STEAP4, suggesting that STEAP1 functions as a ferric reductase in STEAP hetero-trimers. It has been purified using gellan gum microspheres (Batista-Silva et al. 2023). Proteomic analyses of STEAP1 knockdown mutants in human LNCaP prostate cancer cells have been published (Rocha et al. 2023). Proteins involved in endocytosis, RNA transport and apooptosis were up-regulated (including calhepsin B, intersectin-1 (see TC family 1.F.3) and syntaxin 4 (see TC# 8.A.91.1.12) while HPas, PIK3c2a and DIS3 were down regulated (Rocha et al. 2023). The Six-Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is involved in cellular communication, in the stimulation of cell proliferation by increasing Reactive Oxygen Species levels, and in the transmembrane-electron transport and reduction of extracellular metal-ion complexes. STEAP1, which has been purified, is over-expressed in prostate cancer, in contrast with non-tumoral tissues and vital organs, contributing to tumor progression and aggressiveness (Barroca-Ferreira et al. 2022).