TBXAS1

TBXAS1 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, TBXAS1 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 prostglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. TBXAS1 plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke.

Full Name

Thromboxane A Synthase 1

Function

Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation (PubMed:8436233, PubMed:11297515, PubMed:9873013, PubMed:11097184, PubMed:24009185, PubMed:22735388).
Cleaves also 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 (PubMed:11297515, PubMed:9873013, PubMed:22735388).
Additionally, displays dehydratase activity, toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) producing 15-KETE and 15-HETE (PubMed:17459323).

Biological Process

Biological Process cellular chloride ion homeostasisIEA:Ensembl
Biological Process cyclooxygenase pathwayTAS:Reactome
Biological Process icosanoid metabolic processIDA:UniProtKB1 Publication
Biological Process positive regulation of vasoconstrictionIEA:Ensembl
Biological Process prostaglandin biosynthetic processIMP:UniProtKB1 Publication
Biological Process response to ethanolIEA:Ensembl
Biological Process response to fatty acidIEA:Ensembl

Cellular Location

Endoplasmic reticulum membrane

Involvement in disease

Ghosal hematodiaphyseal dysplasia (GHDD):
Rare autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia. Aregenerative anemia is characterized by bone marrow failure, so that functional marrow cells are regenerated slowly or not at all.

Topology

Cytoplasmic: 1-10
Helical: 11-31
Lumenal: 32-75
Helical: 76-96
Cytoplasmic: 97-223
Helical: 224-244
Lumenal: 245-335
Helical: 336-356
Cytoplasmic: 357-533