PTPN5
Description
The PTPN5 (protein tyrosine phosphatase non-receptor type 5) is a protein-coding gene located on chromosome 11.
Protein tyrosine phosphatase non-receptor type 5 is an enzyme encoded by the PTPN5 gene in humans. It is also known as STEP (STriatal-Enriched protein tyrosine Phosphatase) and was the first brain-specific PTP discovered. The human STEP gene is located on chromosome 11p15.2-p15.1 and the mouse gene on chromosome 7B3-B5. The gene is alternatively spliced to produce several isoforms, the most studied being the cytosolic STEP46 protein and the membrane-associated STEP61 protein. As of 2015, seven known targets of STEP have been identified, including ERK1/2, p38, Fyn, Pyk2, PTPα, and the glutamate receptor subunits GluN2B and GluA2. STEP dephosphorylates the kinases (ERK1/2, p38, Fyn, and Pyk2) at a regulatory tyrosine within the kinase activation loop, leading to their inactivation. Dephosphorylation of a regulatory tyrosine on PTPα prevents its translocation from the cytosol to lipid rafts, where it normally activates Fyn. STEP directly inactivates Fyn and prevents the translocation of PTPα to compartments where it activates Fyn. STEP dephosphorylation of GluN2B and GluA2 leads to the internalization of NMDARs (GluN1/GluN2B) and AMPARs (GluA1/GluA2). Therefore, one function of STEP is to oppose synaptic strengthening by inactivating kinases and internalizing receptors that are critical for the development of synaptic strengthening.
PTPN5 is also known as PTPSTEP, STEP, STEP61.
