Phosphohistidine phosphatase 1 (PHPT1)

Phosphohistidine phosphatase 1 (PHPT1) is a small, 14 kDa enzyme consisting of 125 amino acids and is the only known mammalian protein histidine phosphatase[1][2][4][5]. It catalyzes the reversible dephosphorylation of phosphohistidine residues in proteins, a modification that is labile and acid-sensitive[1][2]. PHPT1 displays specificity for phosphohistidine and, to a lesser extent, phospholysine residues, with no activity against the more common phosphoester residues (serine, threonine, tyrosine)[1][2][3][4]. Functionally, PHPT1 regulates the phosphorylation status of proteins involved in cell signaling, potassium ion transport (e.g., dephosphorylating the KCa3.1 channel), metabolic enzymes (e.g., ATP-citrate lyase), and has roles in cytoskeletal organization and cell proliferation[1][2][4]. PHPT1 is expressed in both the cytosol and the nucleus, especially in epithelial cells with high turnover, suggesting a possible role in proliferating cells and possibly in tumor biology[1][4][6]. To date, no clinically approved drugs are known to target PHPT1, although it is of significant interest in basic and translational research for its unique enzyme activity and regulatory mechanisms on histidine phosphorylation[2][4]. No major safety concerns are reported, as no therapies directly target PHPT1 in clinical practice.

Other names

14 kDa phosphohistidine phosphatasePHP14CGI-202HSPC141PHPDKFZp564M173bA216L13.10Protein histidine phosphataseProtein janus-A homologsex-regulated protein janus-aepididymis secretory sperm binding protein Li 132PHEL-S-132P