PTPN1
Description
The PTPN1 (protein tyrosine phosphatase non-receptor type 1) is a protein-coding gene located on chromosome 20.
PTP1B, also known as Protein-tyrosine phosphatase 1B, is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. It is encoded by the PTPN1 gene. PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target for type 2 diabetes. It has also been implicated in the development of breast cancer and explored as a potential therapeutic target in that context. PTP1B was first isolated from a human placental protein extract, but it is expressed in many tissues. It is localized to the cytoplasmic face of the endoplasmic reticulum. PTP1B can dephosphorylate the phosphotyrosine residues of the activated insulin receptor kinase. Genetic ablation of PTPN1 in mice results in enhanced insulin sensitivity. Other tyrosine kinases, including epidermal growth factor receptor, insulin-like growth factor 1 receptor, colony stimulating factor 1 receptor, c-Src, Janus kinase 2, TYK2, and focal adhesion kinase, as well as other tyrosine-phosphorylated proteins, including BCAR1, DOK1, beta-catenin, and cortactin have also been described as PTP1B substrates. The first crystal structure of the PTP1B catalytic domain revealed that the catalytic site exists within a deep cleft of the protein formed by three loops, including the WPD loop with the Asp181 residue, a pTyr loop with the Tyr46 residue, and a Q loop with the Gln262 residue.
PTP1B acts as a regulator of the endoplasmic reticulum unfolded protein response. It dephosphorylates EIF2AK3/PERK, inactivating its protein kinase activity. PTP1B may play a role in CKII- and p60c-src-induced signal transduction cascades. It may also regulate the EFNA5-EPHA3 signaling pathway, which modulates cell reorganization and cell-cell repulsion. PTP1B may further regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.
PTPN1 is also known as PTP1B.
