Metalloreductase STEAP4 (STEAP4)

Metalloreductase STEAP4 (STEAP4) is an integral membrane enzyme in the STEAP family, characterized by six transmembrane domains and a cytoplasmic oxidoreductase domain. It catalyzes the NADPH-dependent reduction of Fe³⁺ to Fe²⁺ and Cu²⁺ to Cu¹⁺, facilitating metal ion uptake and maintaining cellular redox balance. STEAP4 plays crucial roles in metabolic homeostasis, inflammation, and cell proliferation, with expression regulated by cytokines and metabolic stress. Its upregulation is observed in various cancers and metabolic diseases, making it a promising therapeutic target and biomarker. STEAP4 contributes to adipocyte differentiation, lipid storage, and insulin signaling; it also modulates inflammatory pathways like NF‑κB and STAT‑3. Genetic variants of STEAP4 are associated with obesity, type 2 diabetes, and cardiovascular diseases. The structural basis of its metalloreductase activity involves a trimeric arrangement that allows transmembrane electron transfer using FAD and heme cofactors. No specific drugs are approved to target STEAP4, but its multifaceted biological roles and disease involvement underscore its significance in translational medicine and drug discovery.

Other names

STEAP4STAMP2TIARPTNFAIP9SchLAHSix-transmembrane epithelial antigen of prostate 4Six-transmembrane protein of prostate 2Tumor necrosis factor alpha-induced protein 9Tumor necrosis alpha-induced adipose-related proteinSTEAP family member 4Seven chromosome locus associated with HCC