STEP/A0118

Protein tyrosine phosphatase, non-receptor type 5 (striatum-enriched), is also known as STEP (striatum-enriched phosphatase) or A0118, and the gene resides on human chromosome 11.

Protein tyrosine phosphatase, non-receptor type 5 (striatum-enriched), is also known as STEP (striatum-enriched phosphatase) or A0118, and the gene resides on human chromosome 11. STEP belongs to the protein-tyrosine phosphatase family as it contains a tyrosine-protein phosphatase domain. There are three different isoforms of STEP caused by alternatively spliced transcripts of the STEP gene. STEP 46 is the full-length, 46 kDa protein. STEP 20 does not have the conserved tyrosine phosphatase domain. STEP 61 has a 5-prime extended open reading frame but only contains a single tyrosine phosphatase domain. STEP is expressed only in the CNS and is a neural-specific protein-tyrosine phosphatase. STEP plays an important role in regulating the duration of extracellular signal-regulated kinase (ERK) activation and downstream signaling in neurons by dephosphorylating the tyrosine residue in ERK2’s activation domain. STEP can also block a latent neuroprotective response initiated by the mitogen-activated protein kinase (MAPK) pathway, which has the effect of increasing the sensitivity of neurons to status epilepticus-induced excitotoxicity.