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Gene Review

TBXAS1  -  thromboxane A synthase 1 (platelet)

Homo sapiens

Synonyms: BDPLT14, CYP5, CYP5A1, Cytochrome P450 5A1, GHOSAL, ...
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Disease relevance of TBXAS1


Psychiatry related information on TBXAS1


High impact information on TBXAS1

  • Thymidylate synthase (TS, EC catalyzes the reductive methylation of dUMP by CH2H4folate to produce dTMP and H2folate [5].
  • CONCLUSIONS AND IMPLICATIONS: Characterization of tumor TS expression may be of value in identifying patients with advanced head and neck cancer who would benefit from fluoropyrimidine-based neoadjuvant chemotherapy [6].
  • Our results show that virulent Leishmania require at least one copy of dhfr-ts and argue that DHFR-TS plays an unanticipated role in addition to its role in the de novo synthesis of thymidine [7].
  • With either of these agents the SW620 line required higher drug concentrations or longer incubation times than HT29 cells to achieve a given level of fragmentation or cytotoxicity, even though the two cell lines are equally sensitive to FdUrd-induced TS inhibition [8].
  • HT29 and SW620 cells yielded similar fragment size distributions upon treatment with either FdUrd or CB3717 [a folate analog inhibitor of thymidylate synthase (TS)] [8].

Chemical compound and disease context of TBXAS1


Biological context of TBXAS1


Anatomical context of TBXAS1


Associations of TBXAS1 with chemical compounds

  • Characterization of the human gene (TBXAS1) encoding thromboxane synthase [15].
  • Analysis of arachidonate metabolism in cells induced by PMA for 3 and 5 days showed a high level of PGH2 synthesis which exceeded the TXAS capacity for TXA2 synthesis [18].
  • Despite a high TXAS level, uninduced MEG-01 cells synthesized only a small amount of thromboxane A2 (TXA2) due to limited PGHS-1 or PGHS-2 expressions [18].
  • Peptides with either the ultimate 10 or 15 residues of the NH2 terminus of TXS were synthesized and used to produce site-directed antibodies [20].
  • Also, TXA synthase was saturated at lower substrate concentrations than PGE synthase [21].

Physical interactions of TBXAS1


Regulatory relationships of TBXAS1

  • We previously showed that p45 NF-E2 activated the TXAS promoter in hematopoietic cells via binding to the nucleotides -86/-77 from the transcriptional start site [Yaekashiwa and Wang (2002) J. Biol. Chem. 277, 22497-22508] [22].

Other interactions of TBXAS1

  • We conclude that TXAS and PGHS are differentially expressed in MEG-01 during PMA-induced differentiation [18].
  • Only traces of PGHS-2 mRNA and alternate-spliced TXAS mRNA were detected in human platelets [18].
  • A similar differential expression pattern was seen in tumours from patients with different prognosis, in that patients with predicted poor prognosis had higher, but not statistically different, levels of TBXA2R, and significantly lower levels of TBXAS1 (p = 0.008) [1].
  • Mutation of the NF-E2 site greatly reduced TXAS promoter activity in these two types of cells [22].
  • This has led to speculation regarding possible linkage of COX isozymes with PGE and TXA synthase [21].

Analytical, diagnostic and therapeutic context of TBXAS1

  • Levels of TBXA2R and TBXAS1 transcripts were quantified using quantitative real-time RT-PCR analysis and correlated with clinical/pathological information including nodal status, grade, prognosis and long term survival (median follow-up period 120 months) [1].
  • Binding of the peptide antibodies to recombinant TXS in transfected COS-1 and to endogenous TXS in THP-1 cells was analyzed by immunocytochemistry [20].
  • The resulting peptide antibodies were highly specific and recognized human TXS, as shown by binding assays and Western blot analysis [20].
  • Indirect end labeling and ligation-mediated PCR analyses further demonstrated that the occupation of TXAS promoter NF-E2 site was associated with disruption of nucleosomal structure [23].
  • Molecular cloning of human platelet thromboxane A synthase [24].


  1. Expression of thromboxane synthase, TBXAS1 and the thromboxane A2 receptor, TBXA2R, in human breast cancer. Watkins, G., Douglas-Jones, A., Mansel, R.E., Jiang, W.G. International seminars in surgical oncology [electronic resource] : ISSO. (2005) [Pubmed]
  2. Upregulation of thromboxane synthase in human colorectal carcinoma and the cancer cell proliferation by thromboxane A2. Sakai, H., Suzuki, T., Takahashi, Y., Ukai, M., Tauchi, K., Fujii, T., Horikawa, N., Minamimura, T., Tabuchi, Y., Morii, M., Tsukada, K., Takeguchi, N. FEBS Lett. (2006) [Pubmed]
  3. Analysis of Cox-2 and thromboxane synthase expression in pituitary adenomas and carcinomas. Onguru, O., Scheithauer, B.W., Kovacs, K., Vidal, S., Jin, L., Zhang, S., Ruebel, K.H., Lloyd, R.V. Endocr. Pathol. (2004) [Pubmed]
  4. Increased thymidylate synthase mRNA concentration in blood leukocytes following an experimental stressor. Ehrnrooth, E., Zacharia, R., Svendsen, G., Jørgensen, M.M., Yishay, M., Sørensen, B.S., Hjelm Poulsen, J., von der Maase, H. Psychotherapy and psychosomatics. (2002) [Pubmed]
  5. The catalytic mechanism and structure of thymidylate synthase. Carreras, C.W., Santi, D.V. Annu. Rev. Biochem. (1995) [Pubmed]
  6. Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer. Johnston, P.G., Mick, R., Recant, W., Behan, K.A., Dolan, M.E., Ratain, M.J., Beckmann, E., Weichselbaum, R.R., Allegra, C.J., Vokes, E.E. J. Natl. Cancer Inst. (1997) [Pubmed]
  7. Plasticity in chromosome number and testing of essential genes in Leishmania by targeting. Cruz, A.K., Titus, R., Beverley, S.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  8. Variations in patterns of DNA damage induced in human colorectal tumor cells by 5-fluorodeoxyuridine: implications for mechanisms of resistance and cytotoxicity. Canman, C.E., Tang, H.Y., Normolle, D.P., Lawrence, T.S., Maybaum, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  9. Detection of thymidylate synthase expression in lymph node metastases of colorectal cancer can improve the prognostic information. Ohrling, K., Edler, D., Hallström, M., Ragnhammar, P., Blomgren, H. J. Clin. Oncol. (2005) [Pubmed]
  10. Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. Cocconi, G., Cunningham, D., Van Cutsem, E., Francois, E., Gustavsson, B., van Hazel, G., Kerr, D., Possinger, K., Hietschold, S.M. J. Clin. Oncol. (1998) [Pubmed]
  11. Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Johnston, P.G., Lenz, H.J., Leichman, C.G., Danenberg, K.D., Allegra, C.J., Danenberg, P.V., Leichman, L. Cancer Res. (1995) [Pubmed]
  12. Enzyme prodrug gene therapy: synergistic use of the herpes simplex virus-cellular thymidine kinase/ganciclovir system and thymidylate synthase inhibitors for the treatment of colon cancer. Wildner, O., Blaese, R.M., Candotti, F. Cancer Res. (1999) [Pubmed]
  13. Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine. Davies, M.M., Johnston, P.G., Kaur, S., Allen-Mersh, T.G. Clin. Cancer Res. (1999) [Pubmed]
  14. Mapping of the human thromboxane synthase gene (TBXAS1) to chromosome 7q34-q35 by two-color fluorescence in situ hybridization. Chase, M.B., Baek, S.J., Purtell, D.C., Schwartz, S., Shen, R.F. Genomics (1993) [Pubmed]
  15. Characterization of the human gene (TBXAS1) encoding thromboxane synthase. Miyata, A., Yokoyama, C., Ihara, H., Bandoh, S., Takeda, O., Takahashi, E., Tanabe, T. Eur. J. Biochem. (1994) [Pubmed]
  16. Intraluminal pressure modulates eicosanoid enzyme expression in vascular endothelium of intact human conduit vessels at physiological levels of shear stress. Doroudi, R., Gan, L.M., Sjögren, L.S., Jern, S. J. Hypertens. (2002) [Pubmed]
  17. Thromboxane synthase (TBXAS1) polymorphisms in African-American and Caucasian populations: evidence for selective pressure. Ulrich, C.M., Carlson, C.S., Sibert, J., Poole, E.M., Yu, J.H., Wang, L.H., Sparks, R., Potter, J.D., Bigler, J. Hum. Mutat. (2005) [Pubmed]
  18. Differential expression of thromboxane A synthase and prostaglandin H synthase in megakaryocytic cell line. Matijevic-Aleksic, N., Sanduja, S.K., Wang, L.H., Wu, K.K. Biochim. Biophys. Acta (1995) [Pubmed]
  19. Activation of the thromboxane a(2) pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage. Dassesse, T., de Leval, X., de Leval, L., Pirotte, B., Castronovo, V., Waltregny, D. Eur. Urol. (2006) [Pubmed]
  20. Amino-terminal topology of thromboxane synthase in the endoplasmic reticulum. Ruan, K.H., Wang, L.H., Wu, K.K., Kulmacz, R.J. J. Biol. Chem. (1993) [Pubmed]
  21. Differential regulation of prostaglandin E2 and thromboxane A2 production in human monocytes: implications for the use of cyclooxygenase inhibitors. Penglis, P.S., Cleland, L.G., Demasi, M., Caughey, G.E., James, M.J. J. Immunol. (2000) [Pubmed]
  22. Nrf2 regulates thromboxane synthase gene expression in human lung cells. Yaekashiwa, M., Wang, L.H. DNA Cell Biol. (2003) [Pubmed]
  23. Transcriptional control of the human thromboxane synthase gene in vivo and in vitro. Yaekashiwa, M., Wang, L.H. J. Biol. Chem. (2002) [Pubmed]
  24. Molecular cloning of human platelet thromboxane A synthase. Yokoyama, C., Miyata, A., Ihara, H., Ullrich, V., Tanabe, T. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
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