TPBG

Trophoblast glycoprotein
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsTPBG ; 5T4; 5T4AG; M6P1; WAIF1
External IDsOMIM: 190920 MGI: 1341264 HomoloGene: 4859 GeneCards: TPBG Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez716221983
EnsemblENSG00000146242ENSMUSG00000035274
UniProtQ13641Q9Z0L0
RefSeq (mRNA)NM_001166392NM_001164792
RefSeq (protein)NP_001159864NP_001158264
Location (UCSC)Chr 6:
83.07 – 83.08 Mb		Chr 9:
85.84 – 85.85 Mb
PubMed search

Trophoblast glycoprotein, also known as TPBG, 5T4, Wnt-Activated Inhibitory Factor 1 or WAIF1, is a human protein encoded by a TPBG gene.[1] TPBG is an antagonist of Wnt/β-catenin signalling pathway.[2]

5T4 is an antigen expressed in a number of carcinomas.[3] It is an N-glycosylated transmembrane 72 kDa glycoprotein containing eight leucine-rich repeats.[2] 5T4 is often referred to as an oncofetal antigen due to its expression in foetal trophoblast (where it was first discovered) or trophoblast glycoprotein (TPBG).

5T4 is found in tumors including the colorectal, ovarian, and gastric. Its expression is used as a prognostic aid in these cases. It has very limited expression in normal tissue but is widespread in malignant tumors throughout their development.

Its confined expression appears to give 5T4 the potential to be useful in cancer immunotherapy. There has been extensive research into its role in antibody-directed immunotherapy through the use of the high-affinity murine monoclonal antibody, mAb5T4, to deliver response modifiers (such as staphylococcus aureus superantigen) accurately to a tumor.

5T4 is also the target of the cancer vaccine TroVax which is in clinical trials for the treatment of a range of different solid tumour types.

Interactions

TPBG has been shown to interact with GIPC1.[4]

References

  1. ↑ "Entrez Gene: TPBG trophoblast glycoprotein".
  2. ↑ 2.0 2.1 Zhao Y, Malinauskas T, Harlos K, Jones EY (April 2014). "Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1". Structure 22 (4): 612–620. doi:10.1016/j.str.2014.01.009. PMID 24582434.
  3. ↑ Starzynska T, Wiechowska-Kozlowska A, Marlicz K et al. (June 1998). "5T4 oncofetal antigen in gastric carcinoma and its clinical significance". Eur J Gastroenterol Hepatol 10 (6): 479–84. doi:10.1097/00042737-199806000-00008. PMID 9855063.
  4. ↑ Awan, Abida; Lucic Melinda R; Shaw David M; Sheppard Freda; Westwater Caroline; Lyons Steve A; Stern Peter L (Jan 2002). "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis". Biochem. Biophys. Res. Commun. (United States) 290 (3): 1030–6. doi:10.1006/bbrc.2001.6288. ISSN 0006-291X. PMID 11798178.

Further reading

  • Carsberg CJ, Myers KA, Evans GS et al. (1995). "Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane.". J. Cell. Sci. 108. ( Pt 8): 2905–16. PMID 7593330.
  • Myers KA, Rahi-Saund V, Davison MD et al. (1994). "Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats.". J. Biol. Chem. 269 (12): 9319–24. PMID 8132670.
  • Carsberg CJ, Myers KA, Stern PL (1996). "Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells.". Int. J. Cancer 68 (1): 84–92. doi:10.1002/(SICI)1097-0215(19960927)68:1<84::AID-IJC15>3.0.CO;2-6. PMID 8895545.
  • King KW, Sheppard FC, Westwater C et al. (1999). "Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues.". Biochim. Biophys. Acta 1445 (3): 257–70. doi:10.1016/s0167-4781(99)00055-x. PMID 10366710.
  • Awan A, Lucic MR, Shaw DM et al. (2002). "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis.". Biochem. Biophys. Res. Commun. 290 (3): 1030–6. doi:10.1006/bbrc.2001.6288. PMID 11798178.
  • Shaw DM, Woods AM, Myers KA et al. (2002). "Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen.". Biochem. J. 363 (Pt 1): 137–45. doi:10.1042/0264-6021:3630137. PMC 1222460. PMID 11903056.
  • Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Mulryan K, Ryan MG, Myers KA et al. (2003). "Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors.". Mol. Cancer Ther. 1 (12): 1129–37. PMID 12481437.
  • Mungall AJ, Palmer SA, Sims SK et al. (2003). "The DNA sequence and analysis of human chromosome 6.". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404.
  • Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
  • Otsuki T, Ota T, Nishikawa T et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
  • Ward CM, Eastham AM, Stern PL (2006). "Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation.". Exp. Cell Res. 312 (10): 1713–26. doi:10.1016/j.yexcr.2006.02.006. PMID 16616918.
  • Smyth LJ, Elkord E, Taher TE et al. (2006). "CD8 T-cell recognition of human 5T4 oncofetal antigen.". Int. J. Cancer 119 (7): 1638–47. doi:10.1002/ijc.22018. PMID 16646078.
  • Okazaki S, Sekizawa A, Purwosunu Y et al. (2007). "Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women.". Obstetrics and gynecology 110 (5): 1130–6. doi:10.1097/01.AOG.0000286761.11436.67. PMID 17978129.