Metalloreductase STEAP3 (STEAP3)

Metalloreductase STEAP3 is a multipass transmembrane enzyme critical for cellular iron homeostasis, acting as the primary endosomal ferrireductase that reduces ferric (Fe³⁺) to ferrous (Fe²⁺) iron for transferrin-mediated iron uptake in erythroid cells[1][3][4][7]. STEAP3 also exhibits copper reductase activity, suggesting a broader role in metal ion metabolism[4][5]. It interfaces with p53 signaling, affecting apoptosis and cell cycle control, and is highly expressed in macrophages and erythroid precursors[1][8]. STEAP3 deficiency leads to iron distribution defects and anemia; excess or dysregulated STEAP3 expression is implicated in tumor progression, enhanced cancer cell proliferation, immune evasion, and poor prognosis in several cancers including renal, liver, and brain tumors[1][2][6]. Its potential as a therapeutic target is underscored by its involvement in ferroptosis, tumor immune microenvironment regulation, and as a biomarker for patient selection and prognosis in cancer immunotherapy[2][6].

Other names

Six-transmembrane epithelial antigen of prostate 3Tumor suppressor-activated pathway protein 6TSAP6pHydeDudulin-2STMP3AHMIO2STEAP family member 3FerrireductasehTSAP6hpHyde

Modulation of cellular iron content to induce ferroptosis Suppression or inhibition leads to increased lipid peroxidation and cell death (ferroptosis) Upregulation can promote cancer cell survival by increasing iron storage and reducing vulnerability to iron-dependent cell death