TPBG

Trophoblast glycoprotein, also known as TPBG, 5T4, Wnt-Activated Inhibitory Factor 1 or WAIF1, is a human protein encoded by a TPBG gene.[5] TPBG is an antagonist of Wnt/β-catenin signalling pathway.[6]

TPBG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4CNC, 4CNM
Identifiers
Aliases	TPBG, 5T4, 5T4AG, M6P1, WAIF1, trophoblast glycoprotein
External IDs	OMIM: 190920 MGI: 1341264 HomoloGene: 4859 GeneCards: TPBG
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q14.1 Start 82,363,206 bp[1] End 82,370,828 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 E3.1 Start 85,842,380 bp[2] End 85,847,040 bp[2]
RNA expression pattern More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7162	21983
Ensembl	ENSG00000146242 ENSG00000283085	ENSMUSG00000035274
UniProt	Q13641	Q9Z0L0
RefSeq (mRNA)	NM_001166392 NM_006670 NM_001376922	NM_001164792 NM_011627
RefSeq (protein)	NP_001159864 NP_006661 NP_001363851	NP_001158264 NP_035757
Location (UCSC)	Chr 6: 82.36 – 82.37 Mb	Chr 9: 85.84 – 85.85 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Clinical significance

5T4 is an antigen expressed in a number of carcinomas.[7] It is an N-glycosylated transmembrane 72 kDa glycoprotein containing eight leucine-rich repeats.[6] 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 tumours throughout their development. One study found that 5T4 was present in 85% of a cohort of 72 colorectal carcinomas and in 81% of a cohort of 27 gastric carcinomas.[8]

Its confined expression appears to give 5T4 the potential to be a target for T cells 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.[9]

References

1. ENSG00000283085 GRCh38: Ensembl release 89: ENSG00000146242, ENSG00000283085 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035274 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: TPBG trophoblast glycoprotein".
6. Zhao Y, Malinauskas T, Harlos K, Jones EY (Apr 2014). "Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1". Structure. 22 (4): 612–20. doi:10.1016/j.str.2014.01.009. PMC 3988984. PMID 24582434.
7. Starzynska T, Wiechowska-Kozlowska A, Marlicz K, Bromley M, Roberts SA, Lawniczak M, Kolodziej B, Zyluk A, Stern PL (Jun 1998). "5T4 oncofetal antigen in gastric carcinoma and its clinical significance". European Journal of Gastroenterology & Hepatology. 10 (6): 479–84. doi:10.1097/00042737-199806000-00008. PMID 9855063.
8. Starzynska T, Rahi V, Stern PL (Nov 1992). "The expression of 5T4 antigen in colorectal and gastric carcinoma". British Journal of Cancer. 66 (5): 867–9. doi:10.1038/bjc.1992.375. PMC 1977963. PMID 1419629.
9. Awan A, Lucic MR, Shaw DM, Sheppard F, Westwater C, Lyons SA, Stern PL (Jan 2002). "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis". Biochemical and Biophysical Research Communications. 290 (3): 1030–6. doi:10.1006/bbrc.2001.6288. PMID 11798178.

Further reading

• Carsberg CJ, Myers KA, Evans GS, Allen TD, Stern PL (Aug 1995). "Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane". Journal of Cell Science. 108. 108 (8): 2905–16. PMID 7593330.
• Myers KA, Rahi-Saund V, Davison MD, Young JA, Cheater AJ, Stern PL (Mar 1994). "Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats". The Journal of Biological Chemistry. 269 (12): 9319–24. PMID 8132670.
• Carsberg CJ, Myers KA, Stern PL (Sep 1996). "Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells". International Journal of 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, Stern PL, Myers KA (Jun 1999). "Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1445 (3): 257–70. doi:10.1016/s0167-4781(99)00055-x. PMID 10366710.
• Awan A, Lucic MR, Shaw DM, Sheppard F, Westwater C, Lyons SA, Stern PL (Jan 2002). "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis". Biochemical and Biophysical Research Communications. 290 (3): 1030–6. doi:10.1006/bbrc.2001.6288. PMID 11798178.
• Shaw DM, Woods AM, Myers KA, Westwater C, Rahi-Saund V, Davies MJ, Renouf DV, Hounsell EF, Stern PL (Apr 2002). "Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen". The Biochemical Journal. 363 (Pt 1): 137–45. doi:10.1042/0264-6021:3630137. PMC 1222460. PMID 11903056.
• Mulryan K, Ryan MG, Myers KA, Shaw D, Wang W, Kingsman SM, Stern PL, Carroll MW (Oct 2002). "Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors". Molecular Cancer Therapeutics. 1 (12): 1129–37. PMID 12481437.
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (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 Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Ward CM, Eastham AM, Stern PL (Jun 2006). "Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation". Experimental Cell Research. 312 (10): 1713–26. doi:10.1016/j.yexcr.2006.02.006. PMID 16616918.
• Smyth LJ, Elkord E, Taher TE, Jiang HR, Burt DJ, Clayton A, van Veelen PA, de Ru A, Ossendorp F, Melief CJ, Drijfhout JW, Dermime S, Hawkins RE, Stern PL (Oct 2006). "CD8 T-cell recognition of human 5T4 oncofetal antigen". International Journal of Cancer. 119 (7): 1638–47. doi:10.1002/ijc.22018. PMID 16646078.
• Okazaki S, Sekizawa A, Purwosunu Y, Farina A, Wibowo N, Okai T (Nov 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.