Alternative titles; symbols
HGNC Approved Gene Symbol: TPBG
Cytogenetic location: 6q14.1 Genomic coordinates (GRCh38): 6:82,362,983-82,367,420 (from NCBI)
The cell surface antigen defined by monoclonal antibody 5T4 is a 72-kD glycoprotein that is expressed by all types of trophoblasts as early as 9 weeks of development. It is specific for trophoblastic cells except for amniotic epithelium, which is also antigen-positive. In adult tissues, the 5T4 expression is limited to a few epithelial cell types but is found on a variety of carcinomas and has been suggested as a marker for premalignant dysplastic changes in the cervix (Boyle et al., 1990).
By micropeptide sequence analysis, PCR with degenerate primers, and screening of a placenta cDNA library, Myers et al. (1994) obtained a cDNA encoding 5T4, or TPBG. The deduced 420-amino acid protein contains an N-terminal putative signal sequence, a 310-residue extracellular region, a membrane anchorage domain, and a 44-amino acid cytoplasmic tail with a potential phosphorylation site. The extracellular region has 7 potential N-glycosylation sites and 7 leucine-rich repeats, which are located in 2 regions separated by a hydrophilic stretch. Immunoprecipitation analysis showed expression of a 45-kD protein before N-glycosylation, which gives rise to a 72-kD protein. Northern blot analysis revealed expression of a major 2.5-kb transcript, as well as a possible 2.0-kb transcript, in several tumor cell lines.
King et al. (1999) cloned mouse Tpbg, which encodes a protein that is 81% identical to human TPBG. Northern blot and RNase protection analyses detected most abundant expression of Tpbg in mouse embryo and placenta, while in adult mouse it was expressed only in brain and ovary.
By genomic sequence analysis, King et al. (1999) determined that the human and mouse TPBG genes contain 2 exons, the second of which encodes the protein. The promoter region contains no TATA or CAAT boxes, but does have a number of potential SP1-binding sites.
Boyle et al. (1990) stained human-rodent hybrids by indirect immunofluorescence with 5T4 and analyzed them by flow cytometry. Concordance analysis indicated that the M6P1 gene maps to chromosome 6. Similar analysis with translocation hybrids gave a regional assignment to 6q14-q15. M6P1 is distinct from NT5 (129190), which codes for ecto-5-prime-nucleotidase and maps to the same region.
Boyle, J. M., Grzeschik, K.-H., Heath, P. R., Morten, J. E., Stern, P. L. Trophoblast glycoprotein recognised by monoclonal antibody 5T4 maps to human chromosome 6q14-q15. Hum. Genet. 84: 455-458, 1990. [PubMed: 2323778] [Full Text: https://doi.org/10.1007/BF00195819]
King, K. W., Sheppard, F. C., Westwater, C., Stern, P. L., Myers, K. A. Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues. Biochim. Biophys. Acta 1445: 257-270, 1999. [PubMed: 10366710] [Full Text: https://doi.org/10.1016/s0167-4781(99)00055-x]
Myers, K. A., Rahi-Saund, V., Davison, M. D., Young, J. A., Cheater, A. J., Stern, P. L. Isolation of cDNA encoding 5T4 oncofoetal trophoblast glycoprotein: an antigen associated with metastasis contains leucine-rich repeats. J. Biol. Chem. 269: 9319-9324, 1994. [PubMed: 8132670]