Suppressor of T-cell receptor signaling 1 histidine phosphatase domain (Sts-1 HP)

The suppressor of T-cell receptor signaling 1 histidine phosphatase domain (Sts-1 HP) is the C-terminal catalytic domain of the suppressor of T-cell signaling 1 (Sts-1) protein, which is a member of the histidine phosphatase superfamily[1][3][9][10]. Sts-1 acts primarily to negatively regulate signaling pathways downstream of the T-cell receptor by dephosphorylating tyrosine-phosphorylated target proteins, such as the kinase Zap-70, thereby modulating immune cell activation[1][2][5]. The Sts-1 HP domain is highly conserved and features a quartet of critical residues (two histidines and two arginines) essential for its enzymatic phosphatase activity[9]. Functional inactivation of Sts-1 (and its homologue Sts-2) in mice leads to enhanced resistance to certain infections and hyperactive immune signaling[1][3]. Sts-1 is considered a druggable target, and its enzymatic activity can be selectively inhibited by molecules such as PHPS1 and rebamipide derivatives, the latter shown to inhibit Sts-1 in both biochemical and cell-based assays[1][6]. Modulating Sts-1 activity may provide therapeutic benefits in infectious diseases, but systemic inhibition could lead to immune dysregulation or increased risk for autoimmune manifestations due to overactive T-cell responses[1][6].

Other names

Suppressor of T-cell signaling 1 histidine phosphatase domainTULA-2UBASH3BSts-1T-cell ubiquitin ligand-2-associated protein 2

Enzyme inhibition (competitive inhibition of phosphatase activity)