Isoform 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 (By similarity). Acts as a negative regulator of insulin receptor (IR) signaling and is involved in insulin-induced glucose metabolism mainly through direct dephosphorylation and inactivation of IR in hepatocytes and liver. 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 (By similarity). 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+). H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate Monomer. Isoform 2: Homodimer. Can form oligomers. Dimerization is increased by oxidative stress and decreased by EGFR. Isoform 2 interacts with GRB2 (By similarity). Predominantly cytoplasmic. A small fraction is also associated with nucleus and membrane. Insulin can induce translocation to the membrane (By similarity). Isoform 1 is highly expressed in the brain, lung, spleen and testis. Isoform 2 is highly expressed in thymus, spleen and lung. Isoform 1 and isoform 2 are expressed in primary hepatocytes. The 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 (By similarity). A 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. N-glycosylated. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative initiation at Met-85 of isoform 1. Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.