TPST2

TPST2, or tyrosylprotein sulfotransferase 2, is an enzyme in humans encoded by the TPST2 gene. It is one of two Golgi-resident enzymes, together with TPST1, that catalyze the tyrosine sulfation of secreted and membrane proteins. Tyrosine sulfation is a post-translational modification that can influence protein-protein interactions, receptor signaling, and trafficking.

The enzyme is a type II transmembrane protein with a short cytoplasmic N-terminus, a single transmembrane segment, and a luminal catalytic domain facing the Golgi lumen. Within the Golgi, TPST2 transfers sulfate from the donor molecule 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to specific tyrosine residues on substrate proteins, producing tyrosine O-sulfate.

Substrates of TPST2 include a range of secreted and membrane proteins; chemokine receptors such as CCR5 and CXCR4 are known to be tyrosine-sulfated, a modification that enhances ligand binding and function. The substrate repertoire is broad and overlaps with TPST1, contributing to some redundancy and contextual specificity in sulfation patterns across tissues.

Expression of TPST2 is widespread, with variation across tissues. Although TPST1 and TPST2 share catalytic activity, they can display different substrate preferences and regulatory controls, enabling nuanced control of tyrosine sulfation in different biological contexts.

Biological and clinical relevance arises from the role of tyrosine sulfation in modulating protein interactions, signaling pathways, and immune-related processes. Alterations in tyrosine sulfation pathways can impact development, cell adhesion, and host-pathogen interactions, making TPST2 a subject of ongoing research in cell biology and disease.