PTPN2
PTPN2 encodes TC-PTP, a ubiquitous non-receptor tyrosine phosphatase that exists as a nuclear 48 kDa form and an endoplasmic reticulum-anchored 45 kDa form generated by alternative C-terminal splicing. TC-PTP dampens cytokine-driven JAK-STAT signaling by dephosphorylating JAK1, JAK3, STAT1, and STAT3, and it also counteracts insulin and EGF receptor activation, including through the adaptor p52Shc. In T cells it sets signaling thresholds that restrain inflammation, and PTPN2 loss-of-function variants have been associated with autoimmune and inflammatory conditions such as type 1 diabetes and Crohn disease. Recombinant TC-PTP is used to study compartment-specific phosphatase action at the ER and nucleus.
