TPST2 Gene: Function, Location, and Clinical Significance | Biomedical Database

The TPST2 gene encodes tyrosylprotein sulfotransferase 2, an enzyme localized to the trans-Golgi network that catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to tyrosine residues on proteins. This post-translational modification, known as tyrosine O-sulfation, is critical for protein-protein interactions, receptor-ligand binding, and immune cell trafficking. TPST2 is widely expressed and plays roles in development, hemostasis, and inflammatory responses. Mutations in TPST2 have been linked to congenital hypothyroidism and other developmental disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Protein modification; protein sulfation

• Metabolism of cofactors and vitamins (PAPS metabolism)

• Post-translational protein modification

TPST2 is a type II transmembrane protein of the Golgi apparatus, consisting of a short cytoplasmic tail, a transmembrane domain, and a large luminal catalytic domain. It transfers sulfate from PAPS to tyrosine residues in target proteins, a modification essential for protein-protein interactions. The enzyme is involved in the sulfation of chemokine receptors, adhesion molecules, and hormones, influencing immune responses and endocrine function. Structural studies reveal a conserved sulfotransferase domain with a PAPS-binding motif. TPST2 functions as a homodimer and is ubiquitously expressed, with highest levels in thyroid and liver. Its activity is regulated by substrate availability and cellular localization.