Tyrosylprotein sulfotransferase 2 (TPST2)

Tyrosylprotein sulfotransferase 2 (TPST2) is an integral Golgi-resident type II transmembrane enzyme that catalyzes the O-sulfation of tyrosine residues within acidic motifs of secretory and plasma membrane proteins using 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfate donor. This post-translational modification plays a crucial role in modulating extracellular protein–protein interactions, affecting biological processes such as inflammation, leukocyte adhesion, hemostasis, and viral entry (for example, by promoting HIV-1 entry through sulfation of chemokine receptors CCR5 and CXCR4). TPST2, one of only two tyrosylprotein sulfotransferases in humans (along with TPST1), shares tissue distribution and overlapping substrate specificity with TPST1 but has unique physiological roles, including regulation of sperm motility. TPST2's mechanism involves a two-site ping-pong transfer of the sulfuryl group, with specific substrate recognition determinants identified in studies of its crystal structure. Its dysfunction is implicated in rare genetic diseases involving skeletal abnormalities and immunodeficiency, and it may influence susceptibility to infections and inflammation via its effects on protein substrates. No drugs currently target TPST2 specifically, and its widespread modification of substrates suggests therapeutic inhibition would require careful monitoring for safety concerns.

Other names

Protein-tyrosine sulfotransferase 2TPST-2TANGO13BTransport and golgi organization 13 homolog BTyrosylprotein phosphotransferase 2

Catalyzes transfer of a sulfate group from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to tyrosine residues in substrate proteins, affecting their interaction and function. For drugs (no approved drugs), inhibition would decrease tyrosine sulfation of target proteins, altering signal transduction or cell interaction pathways.