This acts as a means of driving selectivity, as substrates containing smaller phosphoresidues cannot reach the site of catalytic activity at the base of the cleft.

The active enzyme is regenerated after the thiophosphate intermediate is hydrolyzed, which is facilitated by the hydrogen bonding interactions of Gln262 and Asp181 that help to position in the water molecule at the desired site of nucleophillic attack.

[30] The thiolate anion form is needed for nucleophilic activity but it is susceptible to oxidation by reactive oxygen species (ROS) in the cell which would render the enzyme non-functional.

This cysteine residue has been shown to oxidize under increased cellular concentrations of hydrogen peroxide (H2O2), produced in response to EGF and insulin signaling.

Gene knockout studies conducted in murine models has provided substantial evidence for the role PTP1B plays in the regulation of insulin signalling and the development of obesity.

[16][17] PTPN1 knockout mice kept on high fat diets showed a resistance to obesity and an increased degree of insulin sensitivity as compared to their wild-type counterparts.

[8] Murine models of HER2 overexpression in conjunction with PTPN1 knockout resulted in delayed tumor growth and with fewer observed metastases to the lung suggesting that PTPN1 may have an oncogenic role in breast cancer.