Src Homology-2 Phosphatase (SHP)

Src homology-2 phosphatases are a family of protein tyrosine phosphatases (PTPs) characterized by the presence of one or more Src homology 2 (SH2) domains. The most studied members are SHP-1 and SHP-2, which play critical roles in cell signaling by modulating processes such as progenitor cell development, cellular growth, tissue inflammation, and chemotaxis. SHP2 contains two tandem N-terminal SH2 domains (N-SH2 and C-SH2), followed by a single catalytic PTP domain. Under basal conditions, the N-SH2 domain blocks the active site of the PTP domain, maintaining an auto-inhibited state. Binding to phosphotyrosine-containing motifs relieves this inhibition and activates the enzyme. Activating mutations in PTPN11/SHP2 are associated with various cancers and germline mutations cause developmental syndromes such as Noonan syndrome.

Other names

SHP-1SHP-2PTPN6PTPN11

Allosteric inhibition (e.g., SHP099), Active site inhibition (e.g., CNBCA)