Thromboxane-A synthase

Thromboxane A synthase 1 (platelet)
Identifiers
Symbols TBXAS1; CYP5; CYP5A1; FLJ52771; GHOSAL; THAS; TS; TXAS; TXS
External IDs OMIM: 274180 MGI: 98497 HomoloGene: 55549 GeneCards: TBXAS1 Gene
EC number 5.3.99.5
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 6916 21391
Ensembl ENSG00000059377 ENSMUSG00000029925
UniProt P24557 Q3UTF0
RefSeq (mRNA) NM_001061.4 NM_011539.3
RefSeq (protein) NP_001052.2 NP_035669.3
Location (UCSC) Chr 7:
139.48 – 139.72 Mb		 Chr 6:
38.83 – 39.03 Mb
PubMed search [1] [2]

Thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A), also known as TBXAS1, is an enzyme that, in humans, is encoded by the TBXAS1 gene.[1][2][3]

Contents

Function

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke. The gene expresses two transcript variants.[1]

Inhibitors

Thromboxane synthase inhibitors are used as antiplatelet drugs. Ifetroban is a potent and selective thromboxane receptor antagonist.[4] Dipyridamole antagonizes this receptor too, but has various other mechanisms of antiplatelet activity as well. Picotamide has activity both as a thromboxane synthase inhibitor and as a thromboxane receptor antagonist.[5]

Pathway

Thromboxane synthesis  
Eicosanoid synthesis  

References

  1. ^ a b "Entrez Gene: TBXAS1 thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6916. 
  2. ^ Yokoyama C, Miyata A, Ihara H, Ullrich V, Tanabe T (August 1991). "Molecular cloning of human platelet thromboxane A synthase". Biochem. Biophys. Res. Commun. 178 (3): 1479–1484. doi:10.1016/0006-291X(91)91060-P. PMID 1714723. http://linkinghub.elsevier.com/retrieve/pii/0006-291X(91)91060-P. 
  3. ^ Baek SJ, Lee KD, Shen RF (September 1996). "Genomic structure and polymorphism of the human thromboxane synthase-encoding gene". Gene 173 (2): 251–256. doi:10.1016/0378-1119(95)00881-0. PMID 8964509. http://linkinghub.elsevier.com/retrieve/pii/0378111995008810. 
  4. ^ Dockens RC, Santone KS, Mitroka JG, Morrison RA, Jemal M, Greene DS, Barbhaiya RH (August 2000). "Disposition of radiolabeled ifetroban in rats, dogs, monkeys, and humans". Drug Metab. Dispos. 28 (8): 973–80. PMID 10901709. 
  5. ^ Ratti S, Quarato P, Casagrande C, Fumagalli R, Corsini A (August 1998). "Picotamide, an antithromboxane agent, inhibits the migration and proliferation of arterial myocytes". Eur. J. Pharmacol. 355 (1): 77–83. doi:10.1016/S0014-2999(98)00467-1. PMID 9754941. 

Further reading

  • Shen RF, Tai HH (1998). "Thromboxanes: synthase and receptors". J. Biomed. Sci. 5 (3): 153–172. doi:10.1007/BF02253465. PMID 9678486. 
  • Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica 28 (12): 1129–1165. doi:10.1080/004982598238868. PMID 9890157. 
  • Wang LH, Kulmacz RJ (2003). "Thromboxane synthase: structure and function of protein and gene". Prostaglandins Other Lipid Mediat. 68-69: 409–422. doi:10.1016/S0090-6980(02)00045-X. PMID 12432933. 
  • Itoh S, Yanagimoto T, Tagawa S et al. (1992). "Genomic organization of human fetal specific P-450IIIA7 (cytochrome P-450HFLa)-related gene(s) and interaction of transcriptional regulatory factor with its DNA element in the 5' flanking region". Biochim. Biophys. Acta 1130 (2): 133–8. PMID 1562592. 
  • Yokoyama C, Miyata A, Ihara H et al. (1991). "Molecular cloning of human platelet thromboxane A synthase". Biochem. Biophys. Res. Commun. 178 (3): 1479–1484. doi:10.1016/0006-291X(91)91060-P. PMID 1714723. 
  • Ohashi K, Ruan KH, Kulmacz RJ et al. (1992). "Primary structure of human thromboxane synthase determined from the cDNA sequence". J. Biol. Chem. 267 (2): 789–93. PMID 1730669. 
  • Jones DA, Fitzpatrick FA, Malcolm KC (1991). "Thromboxane A2 synthesis in human erythroleukemia cells". Biochem. Biophys. Res. Commun. 180 (1): 8–14. doi:10.1016/S0006-291X(05)81247-1. PMID 1930241. 
  • Wang LH, Ohashi K, Wu KK (1991). "Isolation of partial complementary DNA encoding human thromboxane synthase". Biochem. Biophys. Res. Commun. 177 (1): 286–291. doi:10.1016/0006-291X(91)91980-Q. PMID 2043115. 
  • Nüsing R, Schneider-Voss S, Ullrich V (1990). "Immunoaffinity purification of human thromboxane synthase". Arch. Biochem. Biophys. 280 (2): 325–330. doi:10.1016/0003-9861(90)90337-X. PMID 2195994. 
  • Mestel F, Oetliker O, Beck E et al. (1980). "Severe bleeding associated with defective thromboxane synthetase". Lancet 1 (8160): 157. doi:10.1016/S0140-6736(80)90642-X. PMID 6101498. 
  • Miyata A, Yokoyama C, Ihara H et al. (1994). "Characterization of the human gene (TBXAS1) encoding thromboxane synthase". Eur. J. Biochem. 224 (2): 273–279. doi:10.1111/j.1432-1033.1994.00273.x. PMID 7925341. 
  • Wang LH, Tazawa R, Lang AQ, Wu KK (1995). "Alternate splicing of human thromboxane synthase mRNA". Arch. Biochem. Biophys. 315 (2): 273–278. doi:10.1006/abbi.1994.1500. PMID 7986068. 
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • Lee KD, Baek SJ, Shen RF (1994). "Cloning and characterization of the human thromboxane synthase gene promoter". Biochem. Biophys. Res. Commun. 201 (1): 379–387. doi:10.1006/bbrc.1994.1712. PMID 8198598. 
  • Chase MB, Baek SJ, Purtell DC et al. (1993). "Mapping of the human thromboxane synthase gene (TBXAS1) to chromosome 7q34-q35 by two-color fluorescence in situ hybridization". Genomics 16 (3): 771–773. doi:10.1006/geno.1993.1264. PMID 8325653. 
  • Ruan KH, Wang LH, Wu KK, Kulmacz RJ (1993). "Amino-terminal topology of thromboxane synthase in the endoplasmic reticulum". J. Biol. Chem. 268 (26): 19483–90. PMID 8366093. 
  • Tazawa R, Green ED, Ohashi K et al. (1996). "Characterization of the complete genomic structure of human thromboxane synthase gene and functional analysis of its promoter". Arch. Biochem. Biophys. 334 (2): 349–356. doi:10.1006/abbi.1996.0464. PMID 8900410. 
  • Baek SJ, Lee KD, Shen RF (1996). "Genomic structure and polymorphism of the human thromboxane synthase-encoding gene". Gene 173 (2): 251–256. doi:10.1016/0378-1119(95)00881-0. PMID 8964509. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 

See also

External links

Isomerases: intramolecular oxidoreductases (EC 5.3)
5.3.1: Aldoses/Ketoses
5.3.2: Keto/Enol
5.3.3: C=C
5.3.4: S-S
5.3.99: other
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
CYP1
A1 · A2 · B1
CYP2
A6 · A7 · A13 · B6 · C8 · C9 · C18 · C19 · D6 · E1 · F1 · J2 · R1 · S1 · U1 · W1
CYP3 (CYP3A)
A4 · A5 · A7 · A43
CYP4
A11 · A22 · B1 · F2 · F3 · F8 · F11 · F12 · F22 · V2 · X1 · Z1
CYP5-20
CYP5 (A1) · CYP7 (A1, B1) · CYP8 (A1, B1) · CYP11 (A1, B1, B2) · CYP17 (A1) · CYP19 (A1) · CYP20 (A1)
CYP21-51
CYP21 (A2) · CYP24 (A1) · CYP26 (A1, B1, C1) · CYP27 (A1, B1, C1) · CYP39 (A1) · CYP46 (A1) · CYP51 (A1)
Precursor
Prostanoids
Leukotrienes
Ungrouped

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)