Thromboxane-A synthase

Function

Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation. Also cleaves PGH2 to 12-hydroxy-heptadecatrienoicacid (12-HHT) and malondialdehyde, which is known to act as a mediator of DNA damage. 12-HHT and malondialdehyde are formed stoichiometrically in the same amounts as TXA2. Additionally, displays dehydratase activity, toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) producing 15-KETE and 15-HETE.

Classification

Family (Pfam)

PF00067 p450

InterPro

Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf, Cytochrome_P450_3A

Functional cluster

Cytochrome P450 & Heme Enzymes

Gene Ontology · 17

• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005789 endoplasmic reticulum membrane
• GO:0036134 12-hydroxyheptadecatrienoic acid synthase activity
• GO:0020037 heme binding
• GO:0106256 hydroperoxy icosatetraenoate dehydratase activity
• GO:0005506 iron ion binding
• GO:0004497 monooxygenase activity
• GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
• GO:0004796 thromboxane-A synthase activity
• GO:0006690 icosanoid metabolic process
• GO:0030644 intracellular chloride ion homeostasis
• GO:0045907 positive regulation of vasoconstriction
• GO:0001516 prostaglandin biosynthetic process
• GO:0046457 prostanoid biosynthetic process
• GO:0045471 response to ethanol
• GO:0070542 response to fatty acid

Disease associations

• ghosal hematodiaphyseal dysplasia MONDO:0009274

Drugs targeting this protein · 3

• OZAGREL inhibitor
• PICOTAMIDE inhibitor
• TERBOGREL inhibitor

Related proteins · sequence + function similarity

• Thromboxane-A synthase 1.00
• Thromboxane-A synthase 0.98
• Thromboxane-A synthase 0.98
• Thromboxane-A synthase 0.98
• Thromboxane-A synthase 0.98
• Probable cytochrome P450 311a1 0.88
• Probable cytochrome P450 6t1 0.87
• Probable cytochrome P450 6a13 0.87
• Probable cytochrome P450 6t3 0.86
• Probable cytochrome P450 6g2 0.85
• Cytochrome P450 6l1 0.85
• Prostaglandin E2 omega-hydroxylase CYP4F21 0.85

Co-cited proteins · studied together in the literature

• Prostacyclin synthase 1 shared papers
• S-formylglutathione hydrolase 1 shared papers
• Arylacetamide deacetylase 1 shared papers
• Cytochrome P450 7A1 1 shared papers
• Cytochrome P450 2A13 1 shared papers
• Cocaine esterase 1 shared papers
• Cytochrome P450 2A6 1 shared papers
• Cytochrome P450 2B6 1 shared papers
• Apolipoprotein A-IV 1 shared papers
• Granzyme B 1 shared papers
• Dopamine beta-hydroxylase 1 shared papers
• Apolipoprotein C-II 1 shared papers

Literature · 25 cited papers

• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Thromboxane A synthase-independent production of 12-hydroxyheptadecatrienoic acid, a BLT2 ligand. J. Lipid Res. · 2013
• Functional analysis of human thromboxane synthase polymorphic variants. Pharmacogenet. Genomics · 2012
• Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome). Nat. Genet. · 2008
• Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases. Arch. Biochem. Biophys. · 2007
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• The DNA sequence of human chromosome 7. Nature · 2003
• Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population. J. Hum. Genet. · 2003
• Identification of genetic variants in the human thromboxane synthase gene (CYP5A1). Mutat. Res. · 2001
• … and 13 more in the literature graph