FunctionIsoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function. Isoform 2 acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake. Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca(2+).
Tissue specificityExpressed in giant cell tumor (osteoclastoma rich in multinucleated osteoclastic cells).
Sequence similaritiesBelongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily. Contains 2 tyrosine-protein phosphatase domains.
DomainThe tyrosine-protein phosphatase 2 domain (D2) mediates dimerization. The extreme N- and C- termini of the D2 domain act to inhibit dimerization and removal of these sequences increases dimerization and inhibits enzyme activity.
Post-translational modificationsA catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues by tyrosine kinase Neu. Isoform 1 is glycosylated.
Cellular localizationCytoplasm; Cell membrane and Cytoplasm. Predominantly cytoplasmic. A small fraction is also associated with nucleus and membrane. Insulin induces translocation to the membrane.