Alternative titles; symbols
HGNC Approved Gene Symbol: PTPRG
Cytogenetic location: 3p14.2 Genomic coordinates (GRCh38): 3:61,561,571-62,297,609 (from NCBI)
Changes in the level and pattern of phosphorylation of protein tyrosyl residues are implicated in the control of cellular proliferation. The level of phosphorylation within cells is the result of a balance between the opposing activities of protein-tyrosine kinases and protein-tyrosine phosphatases (PTPs). Two distinct classes of PTPs have emerged: one class, the cytoplasmic PTPs, are small soluble proteins; the other class, the receptor PTPs, are large transmembrane proteins. Kaplan et al. (1990) cloned 3 human receptor PTP genes.
Barnea et al. (1993) cloned cDNAs for the human and mouse PTPRG gene (symbolized RPTP-gamma by them) from brain cDNA libraries and analyzed their predicted polypeptide sequences. The human (1,445-amino acid) and mouse (1,442-amino acid) sequences share 95% identity at the amino acid level and predict a putative extracellular domain, a single transmembrane domain, and a cytoplasmic region with 2 tandem catalytic tyrosine phosphatase domains. The extracellular domain contains a stretch of 266 amino acids that are highly similar to the zinc-containing enzyme carbonic anhydrase (114800), suggesting that RPTP-gamma and RPTP-beta (PTPRZ; 176891) represent a subfamily of receptor tyrosine phosphatases.
To facilitate the study of the integrity of the PTPRG gene in kidney tumors, Kastury et al. (1996) determined its structure and its mapped position relative to the translocation breakpoint in 3p14.2 identified in familial RCC. The gene has 30 exons and is approximately 780 kb in size. It is much larger than the other receptor PTP genes, with the CD45 gene (151460) being around 100 kb and the others even smaller.
By analysis of rodent-human somatic cell hybrids retaining overlapping subsets of the entire human genome, LaForgia et al. (1991) mapped the PTPG gene to 3p21-p14. By comparison with other genes mapping to that region, they concluded that PTPG is located in band 3p21 centromeric to the 3p breakpoint in a t(3;8) chromosomal translocation.
Latif et al. (1993) localized the PTPRG gene to 3p14.2 by fluorescence in situ hybridization. D3S1249, which represents the PTPRG locus, was localized between D3S1187 and D3S1188 at a recombination fraction of 0.022 and 0.025, respectively, by linkage analysis using the CEPH pedigree panel (Tory et al., 1992).
Kastury et al. (1996) determined that the 5-prime end of the PTPRG gene maps near but centromeric to the 3p14.2 break in the reciprocal t(3;8) translocation associated with RCC. The FHIT gene (601153) is disrupted by that break.
LaForgia et al. (1991) showed that 1 PTPG allele was lost in 3 of 5 renal carcinoma cell lines and in 5 of 10 lung carcinoma tumor samples tested. PTPG mRNA was expressed in kidney cell lines and lung cell lines but not in several hematopoietic cell lines tested. Thus the PTPG gene appeared to have characteristics suggesting it as a candidate tumor suppressor gene in renal and lung carcinoma.
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; PTPRT, 608712; PTPN3, 176877; 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.
Barnea, G., Silvennoinen, O., Shaanan,B., Honegger, A. M., Canoll, P. D., D'Eustachio, P., Morse, B., Levy, J. B., Laforgia, S., Huebner, K., Musacchio, J. M., Sap, J., Schlessinger, J. Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP-gamma defines a new subfamily of receptor tyrosine phosphatases. Molec. Cell. Biol. 13: 1497-1506, 1993. [PubMed: 8382771] [Full Text: https://doi.org/10.1128/mcb.13.3.1497-1506.1993]
Kaplan, R., Morse, B., Huebner, K., Croce, C., Howk, R., Ravera, M., Ricca, G., Jaye, M., Schlessinger, J. Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked protein-tyrosine-phosphatases expressed in brain. Proc. Nat. Acad. Sci. 87: 7000-7004, 1990. [PubMed: 2169617] [Full Text: https://doi.org/10.1073/pnas.87.18.7000]
Kastury, K., Ohta, M., Lasota, J., Moir, D., Dorman, T., LaForgia, S., Druck, T., Huebner, K. Structure of the human receptor tyrosine phosphatase gamma gene (PTPRG) and relation to the familial RCC t(3;8) chromosome translocation. Genomics 32: 225-235, 1996. [PubMed: 8833149] [Full Text: https://doi.org/10.1006/geno.1996.0109]
LaForgia, S., Morse, B., Levy, J., Barnea, G., Cannizzaro, L. A., Li, F., Nowell, P. C., Boghosian-Sell, L., Glick, J., Weston, A., Harris, C. C., Drabkin, H., Patterson, D., Croce, C. M., Schlessinger, J., Huebner, K. Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21. Proc. Nat. Acad. Sci. 88: 5036-5040, 1991. [PubMed: 1711217] [Full Text: https://doi.org/10.1073/pnas.88.11.5036]
Latif, F., Tory, K., Modi, W., Geil, L., LaForgia, S., Huebner, K., Zbar, B., Lerman, M. I. A Mspl polymorphism and linkage mapping of the human protein-tyrosine phosphatase G (PTPRG) gene. Hum. Molec. Genet. 2: 91, 1993. [PubMed: 7683956] [Full Text: https://doi.org/10.1093/hmg/2.1.91]
Tory, K., Latif, F., Modi, W., Schmidt, L., Wei, M. H., Li, H., Cobler, P., Orcutt, M. L., Delisio, J., Geil, L., Zbar, B., Lerman, M. I. A genetic linkage map of 96 loci on the short arm of human chromosome 3. Genomics 13: 275-286, 1992. [PubMed: 1612588] [Full Text: https://doi.org/10.1016/0888-7543(92)90243-l]
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]