TPBG

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TPBG
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTPBG, 5T4, 5T4AG, M6P1, WAIF1, trophoblast glycoprotein
External IDsOMIM: 190920 MGI: 1341264 HomoloGene: 4859 GeneCards: TPBG
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 9: 85.84 – 85.85 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Clinical significance[edit]

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[edit]

TPBG has been shown to interact with GIPC1.[9]

References[edit]

  1. ^ a b c ENSG00000283085 GRCh38: Ensembl release 89: ENSG00000146242, ENSG00000283085 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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. S2CID 19687036.
  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[edit]