Alternative titles; symbols
HGNC Approved Gene Symbol: PTPRA
Cytogenetic location: 20p13 Genomic coordinates (GRCh38): 20:2,864,184-3,038,669 (from NCBI)
Vital cellular functions, such as cell proliferation and signal transduction, are regulated in part by the balance between the activities of protein-tyrosine kinases (PTKs; see 147795) and protein-tyrosine phosphatases (PTPases; EC 3.1.3.48). PTPases can be divided into 2 classes: small, soluble enzymes containing a single conserved PTPase domain, such as T-cell protein-tyrosine phosphatase (PTPT; 176887), and larger, more complex receptor-linked PTPases containing 2 tandem PTPase domains. PTPRA belongs to the latter group, which also includes leukocyte common antigen (LCA, or PTPRC; 151460) and leukocyte antigen-related tyrosine phosphatase (LAR, or PTPRF; 179590) (summary by Kaplan et al. (1990)).
By screening a hepatoblastoma cell line cDNA library with probes corresponding to the PTPase domains of mouse Ptprc, Jirik et al. (1990) cloned human PTPRA, which they called LRP. The predicted 793-amino acid protein has a calculated molecular mass of 87.5 kD (unglycosylated). The protein contains a leader peptide, followed by a 121-residue extracellular domain, a single transmembrane segment, and 2 tandem intracytoplasmic catalytic domains. The extracellular region has 8 potential N-glycosylation sites and multiple O-glycosylation sites. Northern blot analysis detected 2 LRP transcripts of 3.0 to 3.5 kb in all human cell cell lines examined. Ubiquitous expression was also detected in mouse tissues and cell lines.
By screening a human placenta cDNA library with Drosophila Ptp, Krueger et al. (1990) cloned several PTPases, including PTPRA, which they called PTP-alpha. The deduced 793-amino acid protein has an N-terminal signal peptide, followed by an extracellular domain, a transmembrane segment, and a cytoplasmic region containing duplicate PTPase-like domains. PTP-alpha is rich in serine and threonine and has multiple potential N-glycosylation sites.
By screening a human brainstem cDNA library with a leukocyte common antigen (LCA, or PTPRC; 151460) probe, Kaplan et al. (1990) cloned PTPRA, which they called RPTPase-alpha. The deduced protein contains 802 amino acids. Outside of the extracellular domain, where some variability exists, human PTPRA differs from mouse Ptpra at only 5 amino acids. Northern blot analysis detected 4.3- and 6.3-kb transcripts in various human cell lines and tissues, with the larger transcript being more prevalent in fetal tissues.
Matthews et al. (1990) cloned mouse Ptpra, which they called Lrp. The deduced 793-amino acid protein has an N-terminal leader sequence, followed by an extracellular domain, a membrane-spanning region, and a cytoplasmic domain with 2 conserved tyrosine phosphatase catalytic domains. The extracellular region was predicted to be highly glycosylated. Matthews et al. (1990) also identified an Lrp splice variant containing an insertion that preserves the reading frame but disrupts the first tyrosine phosphatase domain. RNA transfer blot analysis detected wide expression of Lrp in mouse tissues.
Using the cytoplasmic segment of human PTP-alpha expressed in E. coli, Krueger et al. (1990) confirmed that PTP-alpha had robust PTPase activity against phosphorylated test substrates.
By study of rodent-human somatic cell hybrids, Jirik et al. (1990) mapped the PTPRA gene to chromosome 20p13. Other family members located on chromosome 20 include SRC (190090), HCK (142370), and PTP1B (176885). Kaplan et al. (1990) localized the PTPRA gene to chromosome 20pter-20q12 by analysis of its segregation pattern in rodent-human somatic cell hybrids. Rao et al. (1992) regionalized the assignment of PTPA to the distal portion of chromosome 20p (20pter-p12) by both radioactive and fluorescence in situ hybridization. By in situ hybridization, Jirik et al. (1992) localized the PTPA gene to chromosome 20p13.
Schnittger et al. (1992) mapped the mouse Ptpra gene to chromosome 2, confirming the exceptional homology between human chromosome 20 and the distal segment of mouse chromosome 2.
Jirik, F. R., Anderson, L. L., Duncan, A. M. V. The human protein-tyrosine phosphatase PTP-alpha/LRP gene (PTPA) is assigned to chromosome 20p13. Cytogenet. Cell Genet. 60: 117-118, 1992. [PubMed: 1611910] [Full Text: https://doi.org/10.1159/000133317]
Jirik, F. R., Janzen, N. M., Melhado, I. G., Harder, K. W. Cloning and chromosomal assignment of a widely expressed human receptor-like protein-tyrosine phosphatase. FEBS Lett. 273: 239-242, 1990. [PubMed: 2172030] [Full Text: https://doi.org/10.1016/0014-5793(90)81094-5]
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]
Krueger, N. X., Streuli, M., Saito, H. Structural diversity and evolution of human receptor-like protein tyrosine phosphatases. EMBO J. 9: 3241-3252, 1990. [PubMed: 2170109] [Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb07523.x]
Matthews, R. J., Cahir, E. D., Thomas, M. L. Identification of an additional member of the protein-tyrosine-phosphatase family: evidence for alternative splicing in the tyrosine phosphatase domain. Proc. Nat. Acad. Sci. 87: 4444-4448, 1990. [PubMed: 2162042] [Full Text: https://doi.org/10.1073/pnas.87.12.4444]
Rao, V. V. N. G., Loffler, C., Sap, J., Schlessinger, J., Hansmann, I. The gene for receptor-linked protein-tyrosine-phosphatase (PTPA) is assigned to human chromosome 20p12-pter by in situ hybridization (ISH and FISH). Genomics 13: 906-907, 1992. [PubMed: 1639427] [Full Text: https://doi.org/10.1016/0888-7543(92)90186-v]
Schnittger, S., Rao, V. V. N. G., Deutsch, U., Gruss, P., Balling, R., Hansmann, I. PAX1, a member of the paired box-containing class of developmental control genes, is mapped to human chromosome 20p11.2 by in situ hybridization (ISH and FISH). Genomics 14: 740-744, 1992. [PubMed: 1358810] [Full Text: https://doi.org/10.1016/s0888-7543(05)80177-6]