Alternative titles; symbols
HGNC Approved Gene Symbol: PTPRZ1
Cytogenetic location: 7q31.32 Genomic coordinates (GRCh38): 7:121,873,161-122,062,036 (from NCBI)
Phosphorylation of proteins on tyrosine residues plays a key role in the signaling of cell growth, differentiation, and transformation. The net phosphorylation of cellular proteins on tyrosine residues is controlled by the balanced action of protein-tyrosine kinases and protein-tyrosine phosphatases, such as PTPRZ1, present in the cell (Levy et al., 1993).
Krueger and Saito (1992) cloned a cDNA for PTPRZ1, which they called PTP-zeta. The deduced 2,314-amino acid protein contains an N-terminal signal peptide, a 1,616-amino acid extracellular region, a transmembrane domain, and a C-terminal cytoplasmic region. The extracellular region contains an N-terminal sequence homologous to carbonic anhydrases (see 114800) and a 1,048-amino acid sequence without a cysteine. The cytoplasmic portion contains 2 repeated PTPase-like domains. RT-PCR detected high PTP-zeta expression in a glioblastoma cell line, but little to no expression in cell lines from other tissues.
Levy et al. (1993) isolated cDNA clones and deduced the amino acid sequence of PTP-zeta, which contains 2,307 amino acids. Northern blot analysis showed that PTP-zeta is expressed only in the central nervous system (CNS). By in situ hybridization, Levy et al. (1993) localized PTP-zeta expression to different regions of adult brain, including the Purkinje cell layer of the cerebellum, the dentate gyrus, and the subependymal layer of the anterior horn of the lateral ventricle. They stated that this was the first mammalian tyrosine phosphatase whose expression is restricted to the nervous system. High levels of expression in the embryonic brain suggested an important role in CNS development.
Harroch et al. (2000) stated that 3 isoforms of mammalian PTP-zeta are expressed as a result of alternative mRNA splicing: short and long forms that differ by the presence or absence of 860 amino acids in the extracellular region, and a secreted form composed of the extracellular domain only.
Krueger and Saito (1992) expressed the catalytic domain of PTP-zeta in E. coli and found that it had phosphatase activity against a synthetic peptide and a test protein. Mutation analysis showed that only the membrane-proximal PTPase domain was catalytically active.
Levy et al. (1993) mapped the human PTPRZ gene to chromosome 7 by analysis of rodent-human hybrids and regionalized it to 7q31.3-q32 by chromosomal in situ hybridization.
Ariyama et al. (1995) localized the PTPRZ gene to 7q31.3 by somatic cell hybrid mapping and fluorescence in situ hybridization.
Harroch et al. (2000) found that Rptp-beta null mice were viable and fertile and showed no gross anatomic alterations in the nervous system or other organs. The ultrastructure of nerves of the CNS in Rptp-null mice suggested fragility of myelin, but conduction velocity was not altered. Harroch et al. (2000) concluded that RPTP-beta function is not necessary for development of neurons and glia.
Harroch et al. (2002) examined the susceptibility of mice deficient in Pprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (126200). They observed that mice deficient in Ptprz showed impaired recovery from EAE induced by myelin-oligodendrocyte glycoprotein (MOG; 159465) peptide. This sustained paralysis was associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. They further demonstrated that expression of PTPRZ1, the human homolog, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These reports support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease.
Helicobacter pylori is a microaerophilic, gram-negative bacterium that colonizes the gastric mucosa of approximately 50% of the world's population, and is a primary pathogenic factor in benign and malignant gastroduodenal disease. H. pylori induces chronic gastritis in virtually all hosts, yet only a fraction of colonized patients develop peptic ulcer disease (Peek, 2003); see Helicobacter pylori infection, susceptibility to (600263). Fujikawa et al. (2003) presented work in mice deficient in PTPRZ showing that binding of the H. pylori virulence determinant VacA by the phosphatase modifies the phosphorylation pattern of gastric epithelial cell proteins and leads to cellular detachment. As activation of PTPRZ also results in gastric injury and ulceration in vivo, these findings help explain why VacA-expressing strains of H. pylori augment the risk for peptic ulcer disease. H. pylori populations are extremely genetically diverse, which may engender differential host responses that influence clinical outcome. At the same time, the possibility of genetic diversity in the PTPRZ1 gene of the host may influence susceptibility to H. pylori infection and disease.
Ariyama, T., Hasegawa, K., Inazawa, J., Mizuno, K., Ogimoto, M., Katagiri, T., Yakura, H. Assignment of the human protein tyrosine phosphatase, receptor-type, zeta (PTPRZ) gene to chromosome band 7q31.3. Cytogenet. Cell Genet. 70: 52-54, 1995. [PubMed: 7736789] [Full Text: https://doi.org/10.1159/000133990]
Fujikawa, A., Shirasaka, D., Yamamoto, S., Ota, H., Yahiro, K., Fukada, M., Shintani, T., Wada, A., Aoyama, N., Hirayama, T., Fukamachi, H., Noda, M. Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori. Nature Genet. 33: 375-381, 2003. Note: Erratum: Nature Genet. 33: 533 only, 2003. [PubMed: 12598897] [Full Text: https://doi.org/10.1038/ng1112]
Harroch, S., Furtado, G. C., Brueck, W., Rosenbluth, J., Lafaille, J., Chao, M., Buxbaum, J. D., Schlessinger, J. A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions. Nature Genet. 32: 411-414, 2002. [PubMed: 12355066] [Full Text: https://doi.org/10.1038/ng1004]
Harroch, S., Palmeri, M., Rosenbluth, J., Custer, A., Okigaki, M., Shrager, P., Blum, M., Buxbaum, J. D., Schlessinger, J. No obvious abnormality in mice deficient in receptor protein tyrosine phosphatase beta. Molec. Cell. Biol. 20: 7706-7715, 2000. [PubMed: 11003666] [Full Text: https://doi.org/10.1128/MCB.20.20.7706-7715.2000]
Krueger, N. X., Saito, H. A human transmembrane protein-tyrosine-phosphatase, PTP-zeta, is expressed in brain and has an N-terminal receptor domain homologous to carbonic anhydrases. Proc. Nat. Acad. Sci. 89: 7417-7421, 1992. [PubMed: 1323835] [Full Text: https://doi.org/10.1073/pnas.89.16.7417]
Levy, J. B., Canoll, P. D., Silvennoinen, O., Barnea, G., Morse, B., Honegger, A. M., Huang, J.-T., Cannizzaro, L. A., Park, S.-H., Druck, T., Huebner, K., Sap, J., Ehrlich, M., Musacchio, J. M., Schlessinger, J. The cloning of a receptor-type protein tyrosine phosphatase expressed in the central nervous system. J. Biol. Chem. 268: 10573-10581, 1993. [PubMed: 8387522]
Peek, R. M., Jr. Intoxicated cells and stomach ulcers. Nature Genet. 33: 328-330, 2003. [PubMed: 12610544] [Full Text: https://doi.org/10.1038/ng0303-328]