The reference OMIM entry for this protein is 176885

Protein-tyrosine phosphatase, nonreceptor-type, 1; ptpn1
Protein phosphotyrosylphosphatase 1b; ptp1b
Protein-tyrosine phosphatase, placental

CLONING

The phosphorylation of proteins at tyrosine is an important regulatory component in signal transduction, neoplastic transformation, and the control of the mitotic cycle. As in systems regulated by serine or threonine phosphorylation, the phosphorylation of proteins at tyrosine is reversible. The reaction is catalyzed by protein-tyrosine phosphatases (PTPases; protein-tyrosine phosphate phosphohydrolase; EC 3.1.3.48). These enzymes appear to be highly specific for phosphotyrosyl proteins and bear little resemblance to either the protein-serine phosphatases or protein-threonine phosphatases or the acid and alkaline phosphatases. Tonks et al. (1988) and Charbonneau et al. (1989) purified a form of this enzyme, PTP1B, from human placenta and determined its amino acid sequence. The protein sequence was found to be unrelated to those of other known phosphatases but similar to the common leukocyte antigen (CD45; 151460) and to LAR (179590). Chernoff et al. (1990) cloned cDNA for PTP1B. The sequence predicted that the protein contains an additional 114 amino acids not present in the reported peptide sequence. Brown-Shimer et al. (1990) isolated a cDNA clone for PTP1B. The translation deduced from the 1,305-nucleotide open reading frame predicted a protein containing 435 amino acids and having a molecular mass of 49,966 Da. The N-terminal 321 amino acids deduced from the cDNA sequence were identical to the empirically determined sequence reported by Charbonneau et al. (1989).

GENE FAMILY

PTP1B is the founding member (Tonks et al., 1988) of a family of more than 40 PTPases, including receptor-like transmembrane forms and cytosolic enzymes, that are characterized by homologous catalytic domains of approximately 240 amino acids.

GENE FUNCTION

Fukada and Tonks (2003) found that overexpression of Yb1 (NSEP1; 154030) in Rat1 cells resulted in increased Ptp1b expression. Depletion of Yb1 decreased Ptp1b expression, increased sensitivity to insulin, and enhanced signaling through the cytokine receptor gp130 (IL6ST; 600694), which was suppressed by reexpression of Ptp1b. Fukada and Tonks (2003) also found a correlation between expression of PTP1B and YB1 in several human cancer cell lines and in an animal model of type II diabetes (125853). They concluded that YB1 is an important regulator of PTP1B expression. In order to test whether PTP1B is spatially regulated, Yudushkin et al. (2007) developed a method based on Forster resonant energy transfer for imaging enzyme-substrate intermediates in live cells. Yudushkin et al. (2007) observed the establishment of a steady-state enzyme-substrate gradient across the cell. This gradient exhibited robustness to cell-to-cell variability, growth factor activation, and receptor tyrosine kinase localization, which demonstrated spatial regulation of PTP1B activity. Yudushkin et al. (2007) postulated that such regulation may be important for generating distinct cellular environments that permit receptor tyrosine kinase signal transduction and mediate its eventual termination.

BIOCHEMICAL FEATURES

To provide insight into the structural basis of substrate recognition by PTP1B, Jia et al. (1995) determined the structures of a catalytically inactive cys215-to-ser mutant form of the enzyme complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the epidermal growth factor receptor (131550). The protein-tyrosine phosphatase PTP1B is re ... More on the omim web site

Subscribe to this protein entry history

July 1, 2020: Protein entry updated
Automatic update: OMIM entry 176885 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).