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TSAP6 (dudulin 2 isoform B) The dominant ferrireductase (metaloreductase) of the human erythroid transferrin cycle (Sendamarai et al. 2008). Also called six transmembrane epithelial antigen of protein-3 (Steap3) and tumor suppressor-activated pathway protein-6 (TSAP6). Consists primarily of a YedZ domain (9.B.43)

Metazoa, Chordata
TSAP6 of Homo sapiens (NM_018234)

Metalloreductase STEAP2 or STAMP1 (EC 1.16.1.-) (Prostate cancer-associated protein 1) (Protein up-regulated in metastatic prostate cancer; PUMPCn) Six-transmembrane epithelial antigen of prostate 2) (6TMS protein of prostate 1). Membrane cholesterol modulates the STEAP2 conformation during intracellular trafficking, leading to a broad subcellular distribution (Hasegawa et al. 2018). The molecular mechanism and function of STEAPs in the occurrence and development of different cancers have been reviewed (Chen et al. 2021).

Metazoa, Chordata
STEAP2 of Homo sapiens

STEAP4 metaloreductase of 459 aas.  It is also called Stamp2, TNFAIP9. It is an integral membrane protein that functions as an NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe3+ chelate that is bound on the other side of the membrane. STAMP2 mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe3+ chelate (Oosterheert et al. 2018) and can also reduce Cu2+ to Cu1+. It plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses and is associated with obesity and insulin-resistance (Zhang et al. 2008, Arner et al. 2008). It is also involved in inflammatory arthritis, through the regulation of inflammatory cytokines (Inoue et al. 2009). It inhibits anchorage-independent cell proliferation (Tamura and Chiba 2009). The crystal structure is known (Gauss et al. 2013). Hepatic STAMP2 mediates recombinant FGF21-induced improvement of hepatic iron overload in nonalcoholic fatty liver disease (Kim et al. 2020).

Metazoa, Chordata
STEAP4 of Homo sapiens

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).


Metazoa, Chordata
STEAP of Homo sapiens (AAH11802)

Uncharacterized protein of 230 aas and 6 TMSs.

Candidatus Wolfebacteria
UP of Candidatus Wolfebacteria bacterium