Alternative titles; symbols
HGNC Approved Gene Symbol: PTPN3
Cytogenetic location: 9q31.3 Genomic coordinates (GRCh38): 9:109,375,694-109,538,420 (from NCBI)
Yang and Tonks (1991) isolated from HeLa cells a cDNA for a nontransmembrane protein homologous to the protein-tyrosine phosphatases. Its sequence suggested that it may act at the interface between the plasma membrane and the cytoskeleton and may, therefore, function in maintaining the integrity of the cytoskeleton. The N-terminal segment displayed homology to the domains in the cytoskeleton-associated proteins band 4.1 (130500), ezrin (123900), and talin (186745). They referred to the deduced protein as PTPH1 (H = HeLa); PTPN3 is the gene symbol adopted by the HGM nomenclature committee.
By Northern blot analysis, Itoh et al. (1993) detected only low abundance of a 4.3-kb PTPH1 transcript in normal colon. RT-PCR analysis, however, detected expression in a wide variety of tumor cell lines.
Zhang et al. (1999) created a substrate-trapping mutant of PTPH1 by introducing an asp811-to-ala mutation (D811A). The D811A mutant interacted primarily with VCP (601023) in vitro but not in cells. A double mutant of PTPH1 (D811A/tyr676 to phe) had a marked reduction in phosphotyrosine content, specifically trapped VCP in vivo, and recognized the C-terminal tyrosines of VCP. Like wildtype PTPH1, the double mutant also inhibited cell proliferation. Immunoblot analysis showed that wildtype PTPH1 specifically dephosphorylates VCP. Zhang et al. (1999) concluded that PTPH1 exerts its effects on cell growth through dephosphorylation of VCP.
Using FISH, Itoh et al. (1993) mapped the PTPN3 gene to chromosome 9q31.
Wang et al. (2004) performed a mutational analysis of the tyrosine phosphatase gene superfamily in human cancers and identified 83 somatic mutations in 6 protein-tyrosine phosphatases (PTPRF, 179590; PTPRG, 176886; PTPRT, 608712; PTPN3; PTPN13, 600267; and PTPN14, 603155), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice site alterations predicted to result in truncated proteins lacking phosphatase activity. Wang et al. (2004) biochemically examined 5 missense mutations in PTPRT, the most commonly altered protein-tyrosine phosphatase, and found that they reduced phosphatase activity. Expression of wildtype but not a mutant PTPRT in human cancer cells inhibited cell growth. Wang et al. (2004) concluded that their observations suggested that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.
Itoh, F., Ikuta, S., Hinoda, Y., Arimura, Y., Ohe, M., Adachi, M., Ariyama, T., Inazawa, J., Imai, K., Yachi, A. Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal-associated proteins. Int. J. Cancer 55: 947-951, 1993. [PubMed: 8253532] [Full Text: https://doi.org/10.1002/ijc.2910550612]
Wang, Z., Shen, D., Parsons, D. W., Bardelli, A., Sager, J., Szabo, S., Ptak, J., Silliman, N., Peters, B. A., van der Heijden, M. S., Parmigiani, G., Yan, H., Wang, T.-L., Riggins, G., Powell, S. M., Willson, J. K. V., Markowitz, S., Kinzler, K. W., Vogelstein, B., Velculescu, V. E. Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304: 1164-1166, 2004. [PubMed: 15155950] [Full Text: https://doi.org/10.1126/science.1096096]
Yang, Q., Tonks, N. K. Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin, and talin. Proc. Nat. Acad. Sci. 88: 5949-5953, 1991. [PubMed: 1648725] [Full Text: https://doi.org/10.1073/pnas.88.14.5949]
Zhang, S.-H., Liu, J., Kobayashi, R., Tonks, N. K. Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPH1. J. Biol. Chem. 274: 17806-17812, 1999. [PubMed: 10364224] [Full Text: https://doi.org/10.1074/jbc.274.25.17806]