Steap

Steap, most often encountered in scientific literature as STEAP, refers to a family of metalloreductase proteins in humans and other vertebrates. The name stands for Six-Transmembrane Epithelial Antigen of the Prostate, reflecting their initial identification in prostate-derived tissues. STEAP proteins are involved in the metabolism and transport of metal ions, particularly iron and copper, by catalyzing the reduction of ferric to ferrous iron, a step that facilitates uptake through other metal transport systems.

Structure and members

STEAP proteins are predicted to span the cellular membrane six times, with both their N- and C- termini located in the cytoplasm. They bind cofactors such as flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide phosphate (NADPH), which enable electron transfer during metal reduction. In mammals, the core family is commonly described as STEAP1 through STEAP4, with additional related genes and pseudogenes noted in various studies. The precise contribution of each member to metal homeostasis can vary by tissue and context.

Function and clinical relevance

The primary role of STEAP proteins is to act as ferrireductases and, for some members, as cuprireductases, thereby supporting cellular iron and copper uptake. Their activity links to broader iron metabolism pathways, including interactions with transporters such as DMT1 and related systems. Expression of STEAP proteins is widespread but often enriched in certain tissues, including the prostate. Several STEAP members show altered expression in cancers, where they may influence cell proliferation, migration, and tumor progression. Consequently, STEAP proteins are investigated as potential biomarkers and, in some contexts, as therapeutic targets.

History

The STEAP designation originated from their discovery in prostate-related research during the late 1990s and early 2000s, highlighting their epithelial origin and membrane localization. Ongoing research continues to clarify their specific physiological roles and their contributions to disease.