| IED ID | IndEnz0010001645 |
| Enzyme Type ID | esterase001645 |
| Protein Name |
Thromboxane-A synthase TXA synthase TXS EC 5.3.99.5 Cytochrome P450 5A1 Hydroperoxy icosatetraenoate dehydratase EC 4.2.1.152 |
| Gene Name | TBXAS1 CYP5 CYP5A1 TXAS |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MEALGFLKLEVNGPMVTVALSVALLALLKWYSTSAFSRLEKLGLRHPKPSPFIGNLTFFRQGFWESQMELRKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRMASGLEFKSVADSVLFLRDKRWEEVRGALMSAFSPEKLNEMVPLISQACDLLLAHLKRYAESGDAFDIQRCYCNYTTDVVASVAFGTPVDSWQAPEDPFVKHCKRFFEFCIPRPILVLLLSFPSIMVPLARILPNKNRDELNGFFNKLIRNVIALRDQQAAEERRRDFLQMVLDARHSASPMGVQDFDIVRDVFSSTGCKPNPSRQHQPSPMARPLTVDEIVGQAFIFLIAGYEIITNTLSFATYLLATNPDCQEKLLREVDVFKEKHMAPEFCSLEEGLPYLDMVIAETLRMYPPAFRFTREAAQDCEVLGQRIPAGAVLEMAVGALHHDPEHWPSPETFNPERFTAEARQQHRPFTYLPFGAGPRSCLGVRLGLLEVKLTLLHVLHKFRFQACPETQVPLQLESKSALGPKNGVYIKIVSR |
| Enzyme Length | 533 |
| Uniprot Accession Number | P24557 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=prostaglandin H2 = thromboxane A2; Xref=Rhea:RHEA:17137, ChEBI:CHEBI:57405, ChEBI:CHEBI:57445; EC=5.3.99.5; Evidence={ECO:0000269|PubMed:11097184, ECO:0000269|PubMed:11297515, ECO:0000269|PubMed:22735388, ECO:0000269|PubMed:24009185, ECO:0000269|PubMed:8436233, ECO:0000269|PubMed:9873013};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17138; Evidence={ECO:0000305|PubMed:11297515, ECO:0000305|PubMed:8436233, ECO:0000305|PubMed:9873013}; CATALYTIC ACTIVITY: Reaction=prostaglandin H2 = (12S)-hydroxy-(5Z,8E,10E)-heptadecatrienoate + malonaldehyde; Xref=Rhea:RHEA:48644, ChEBI:CHEBI:57405, ChEBI:CHEBI:90694, ChEBI:CHEBI:566274; Evidence={ECO:0000269|PubMed:11297515, ECO:0000269|PubMed:22735388, ECO:0000269|PubMed:9873013}; CATALYTIC ACTIVITY: Reaction=a hydroperoxyeicosatetraenoate = an oxoeicosatetraenoate + H2O; Xref=Rhea:RHEA:55556, ChEBI:CHEBI:15377, ChEBI:CHEBI:59720, ChEBI:CHEBI:131859; EC=4.2.1.152; Evidence={ECO:0000269|PubMed:17459323};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55557; Evidence={ECO:0000305|PubMed:17459323}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636, ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446; Evidence={ECO:0000269|PubMed:17459323};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; Evidence={ECO:0000305|PubMed:17459323}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 = (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + A + H2O; Xref=Rhea:RHEA:48856, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:57409, ChEBI:CHEBI:57446; Evidence={ECO:0000269|PubMed:17459323};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48857; Evidence={ECO:0000305|PubMed:17459323}; |
| DNA Binding | |
| EC Number | 5.3.99.5; 4.2.1.152 |
| Enzyme Function | 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). {ECO:0000269|PubMed:11097184, ECO:0000269|PubMed:11297515, ECO:0000269|PubMed:17459323, ECO:0000269|PubMed:22735388, ECO:0000269|PubMed:24009185, ECO:0000269|PubMed:8436233, ECO:0000269|PubMed:9873013}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000305}. |
| nucleotide Binding | |
| Features | Alternative sequence (4); Chain (1); Erroneous gene model prediction (1); Erroneous initiation (17); Metal binding (1); Mutagenesis (9); Natural variant (30); Sequence conflict (19); Topological domain (5); Transmembrane (4) |
| Keywords | Alternative splicing;Direct protein sequencing;Disease variant;Endoplasmic reticulum;Fatty acid biosynthesis;Fatty acid metabolism;Heme;Iron;Isomerase;Lipid biosynthesis;Lipid metabolism;Lyase;Membrane;Metal-binding;Monooxygenase;Oxidoreductase;Prostaglandin biosynthesis;Prostaglandin metabolism;Reference proteome;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:8366093}; Multi-pass membrane protein {ECO:0000255}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11782360; 11956185; 12432933; 15067173; 15870920; 16357168; 18985028; 19046748; 19064572; 19114962; 19124506; 19276290; 19343046; 19403042; 19729601; 19913121; 20227257; 20379614; 20383787; 20452482; 20628086; 20647010; 20673868; 20677014; 20931532; 21215134; 21388528; 21449675; 22493072; 23763970; 24556579; 26027242; 26117917; 26252103; 26974824; 28108096; 28704403; 28868793; 30039765; 31026093; 33185009; 33527589; 33595912; |
| Motif | |
| Gene Encoded By | |
| Mass | 60,518 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=80 uM for 15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15-HPETE) {ECO:0000269|PubMed:17459323}; KM=32 uM for prostaglandin H2 {ECO:0000269|PubMed:22735388}; KM=20 uM for prostaglandin H2 {ECO:0000269|PubMed:9873013}; Vmax=12 umol/min/mg enzyme for prostaglandin H2 as substrate {ECO:0000269|PubMed:9873013}; |
| Metal Binding | METAL 479; /note=Iron (heme axial ligand); /evidence=ECO:0000250|UniProtKB:P14779 |
| Rhea ID | RHEA:17137; RHEA:17138; RHEA:48644; RHEA:55556; RHEA:55557; RHEA:48636; RHEA:48637; RHEA:48856; RHEA:48857 |
| Cross Reference Brenda |