THAS_PIG
ID THAS_PIG Reviewed; 534 AA.
AC P47787;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Thromboxane-A synthase;
DE Short=TXA synthase;
DE Short=TXS;
DE EC=5.3.99.5 {ECO:0000269|PubMed:3745158};
DE AltName: Full=Cytochrome P450 5A1;
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase;
DE EC=4.2.1.152;
GN Name=TBXAS1; Synonyms=CYP5, CYP5A1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=8144035; DOI=10.1016/0378-1119(94)90555-x;
RA Shen R.F., Zhang L., Baek S.J., Tai H.H., Lee K.D.;
RT "The porcine thromboxane synthase-encoding cDNA: sequence, mRNA expression
RT and enzyme production in Sf9 insect cells.";
RL Gene 140:261-265(1994).
RN [2]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=3745158; DOI=10.1016/s0021-9258(18)67284-9;
RA Shen R.F., Tai H.H.;
RT "Immunoaffinity purification and characterization of thromboxane synthase
RT from porcine lung.";
RL J. Biol. Chem. 261:11592-11599(1986).
CC -!- FUNCTION: Catalyzes the conversion of prostaglandin H2 (PGH2) to
CC thromboxane A2 (TXA2), a potent inducer of blood vessel constriction
CC and platelet aggregation (PubMed:3745158). Cleaves also PGH2 to 12-
CC hydroxy-heptadecatrienoicacid (12-HHT) and malondialdehyde, which is
CC known to act as a mediator of DNA damage. 12-HHT and malondialdehyde
CC are formed stoichiometrically in the same amounts as TXA2.
CC Additionally, displays dehydratase activity, toward (15S)-hydroperoxy-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) producing 15-KETE and
CC 15-HETE (By similarity). {ECO:0000250|UniProtKB:P24557,
CC ECO:0000269|PubMed:3745158}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = thromboxane A2; Xref=Rhea:RHEA:17137,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57445; EC=5.3.99.5;
CC Evidence={ECO:0000269|PubMed:3745158};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17138;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = (12S)-hydroxy-(5Z,8E,10E)-
CC heptadecatrienoate + malonaldehyde; Xref=Rhea:RHEA:48644,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:90694, ChEBI:CHEBI:566274;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a hydroperoxyeicosatetraenoate = an oxoeicosatetraenoate +
CC H2O; Xref=Rhea:RHEA:55556, ChEBI:CHEBI:15377, ChEBI:CHEBI:59720,
CC ChEBI:CHEBI:131859; EC=4.2.1.152;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55557;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 =
CC (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + A + H2O;
CC Xref=Rhea:RHEA:48856, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57409, ChEBI:CHEBI:57446;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48857;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P24557};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12 uM for prostaglandin H2 {ECO:0000269|PubMed:3745158};
CC Vmax=0.23 umol/min/mg enzyme for prostaglandin H2 as substrate
CC {ECO:0000269|PubMed:3745158};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P24557}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P24557}; Multi-pass membrane protein
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in lung, kidney and thymus.
CC {ECO:0000269|PubMed:8144035}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L13128; AAA31127.1; -; mRNA.
DR RefSeq; NP_999211.1; NM_214046.1.
DR AlphaFoldDB; P47787; -.
DR SMR; P47787; -.
DR BioGRID; 1149247; 1.
DR STRING; 9823.ENSSSCP00000017486; -.
DR PaxDb; P47787; -.
DR PeptideAtlas; P47787; -.
DR Ensembl; ENSSSCT00070044468; ENSSSCP00070037469; ENSSSCG00070022371.
DR GeneID; 397112; -.
DR KEGG; ssc:397112; -.
DR CTD; 6916; -.
DR eggNOG; KOG0158; Eukaryota.
DR InParanoid; P47787; -.
DR OMA; WPHPETF; -.
DR OrthoDB; 786853at2759; -.
DR Reactome; R-SSC-211979; Eicosanoids.
DR Reactome; R-SSC-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 18.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036134; F:12-hydroxyheptadecatrienoic acid synthase activity; IEA:RHEA.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0106256; F:hydroperoxy icosatetraenoate dehydratase activity; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0004796; F:thromboxane-A synthase activity; IBA:GO_Central.
DR GO; GO:0006690; P:icosanoid metabolic process; ISS:UniProtKB.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 2.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Heme; Iron; Isomerase; Lipid biosynthesis; Lipid metabolism; Lyase;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..534
FT /note="Thromboxane-A synthase"
FT /id="PRO_0000052258"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P24557"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..75
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P24557"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P24557"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..336
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P24557"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 358..534
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P24557"
FT BINDING 480
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P14779"
SQ SEQUENCE 534 AA; 60485 MW; 635347A1B3508715 CRC64;
MEVLGFLSPE LNGPMVTMAL AVVLLALLKW YSTSAFSRLE KLGIRHPKPS PFIGNLTFFR
QGFWESHMEL RKQYGPLSGY YLGRRMIVVI SDPDMIKQVL AEKFSNFTNR MATGLESKPV
ADSILFLRDK RWEEVRSVLT SAFSPKKLNK LTPLISQACD LLLAHLERYA ESGDAFDIQR
CYCCYTTDVV ASVAFGTQVN SSEEPEHPFV KHCRRFFAFS VPRLILVLIL SFPSIMVPLA
RILPNKKRDE VNGFFNKLIR NVIALRDQQA AEERRQDFLQ MVLDLRHSAP SVGVENFDIV
RQAFSSAKGC PADPSQPHLP RPLSKPLTVD EVVGQAFLFL IAGYEIITNT LSFVTYLLAT
NPDCQEKLLR EVDDFSKKHP SPEHCSLQQG LPYLDMVLSE TLRMYPPAFR FTREAARDCE
VLGQRIPAGT VLEVAVGALH HDPKHWPHPE TFDPERFTAE AQRLQQPFTY LPFGAGPRSC
LGVQLGLLEI KLTLLHILRK FRFEACPETQ VPLQLESKSA LSPKNGVYIR IVPR
