Phosphotyrosyl phosphate activator (PTPA), also known as protein phosphatase 2A (PP2A) phosphatase activator, is an alpha-helical protein which consists of three distinct domains: the core, the linker and the lid. This superfamily consists of the lid domain of PTPA, located usually at the C-terminus.

PTPA proteins stimulate the phosphotyrosyl phosphatase (PTPase) activity of the dimeric form of PP2A. Together, PTPA and PP2A constitute an ATPase and it has been suggested that PTPA alters the relative specificity of PP2A from phosphoserine/phosphothreonine substrates to phosphotyrosine substrates in an ATP-hydrolysis-dependent manner. PTPase activity in PP2A (in vitro) is relatively low when compared to the better recognised phosphoserine/ threonine protein phosphorylase activity. It also reactivates the serine/threonine phosphatase activity of an inactive form of PP2A. PTPA has been suggested to play a role in the insertion of metals to the PP2A catalytic subunit (PP2Ac) active site, to act as a chaperone, and more recently, to have peptidyl prolyl cis/trans isomerase activity that specifically targets human PP2Ac. Basal expression of PTPA depends on the activity of a ubiquitous transcription factor, Yin Yang 1 (YY1). The tumour suppressor protein p53 can inhibit PTPA expression through an unknown mechanism that negatively controls YY1.

PFAM:PF03095, INTERPRO:IPR004327, INTERPRO:IPR037218,PMID:16916641,PMID:16885030