THAS_MOUSE
ID THAS_MOUSE Reviewed; 533 AA.
AC P36423; P97505;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Thromboxane-A synthase;
DE Short=TS;
DE Short=TXA synthase;
DE Short=TXS;
DE EC=5.3.99.5 {ECO:0000269|PubMed:7688225};
DE AltName: Full=Cytochrome P450 5A1;
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase;
DE EC=4.2.1.152 {ECO:0000250|UniProtKB:P24557};
GN Name=Tbxas1; Synonyms=Cyp5, Cyp5a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND
RP FUNCTION.
RC STRAIN=CD-1; TISSUE=Lung;
RX PubMed=7688225; DOI=10.1006/bbrc.1993.1884;
RA Zhang L., Chase M.B., Shen R.F.;
RT "Molecular cloning and expression of murine thromboxane synthase.";
RL Biochem. Biophys. Res. Commun. 194:741-748(1993).
RN [2]
RP SEQUENCE REVISION.
RA Zhang L.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=9367676; DOI=10.1006/geno.1997.4982;
RA Zhang L., Xiao H., Schultz R.A., Shen R.-F.;
RT "Genomic organization, chromosomal localization, and expression of the
RT murine thromboxane synthase gene.";
RL Genomics 45:519-528(1997).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=15010374; DOI=10.1182/blood-2003-10-3661;
RA Yu I.S., Lin S.R., Huang C.C., Tseng H.Y., Huang P.H., Shi G.Y., Wu H.L.,
RA Tang C.L., Chu P.H., Wang L.H., Wu K.K., Lin S.W.;
RT "TXAS-deleted mice exhibit normal thrombopoiesis, defective hemostasis, and
RT resistance to arachidonate-induced death.";
RL Blood 104:135-142(2004).
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. Cleaves also PGH2 to 12-hydroxy-
CC heptadecatrienoicacid (12-HHT) and malondialdehyde, which is known to
CC act as a mediator of DNA damage. 12-HHT and malondialdehyde are formed
CC stoichiometrically in the same amounts as TXA2. Additionally, displays
CC dehydratase activity, toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-
CC eicosatetraenoate (15(S)-HPETE) producing 15-KETE and 15-HETE.
CC {ECO:0000250|UniProtKB:P24557}.
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:7688225};
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 -!- 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 primarily in lung, kidney, and spleen.
CC {ECO:0000269|PubMed:7688225}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable, fertile and exhibited
CC no gross abnormalities in size, body weight, and anatomical features of
CC major organs. However deficency causes a mild hemostatic defect and
CC protects mice against arachidonate-induced shock and death.
CC {ECO:0000269|PubMed:15010374}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; L18868; AAB39850.1; -; mRNA.
DR EMBL; U41397; AAB87704.1; -; Genomic_DNA.
DR EMBL; U41326; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41327; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41328; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41329; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41330; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41331; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41332; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41333; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41334; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41335; AAB87704.1; JOINED; Genomic_DNA.
DR EMBL; U41336; AAB87704.1; JOINED; Genomic_DNA.
DR CCDS; CCDS20018.1; -.
DR PIR; JN0683; JN0683.
DR RefSeq; NP_035669.3; NM_011539.3.
DR RefSeq; XP_011239582.1; XM_011241280.2.
DR RefSeq; XP_017176988.1; XM_017321499.1.
DR RefSeq; XP_017176989.1; XM_017321500.1.
DR AlphaFoldDB; P36423; -.
DR SMR; P36423; -.
DR STRING; 10090.ENSMUSP00000003017; -.
DR BindingDB; P36423; -.
DR iPTMnet; P36423; -.
DR PhosphoSitePlus; P36423; -.
DR MaxQB; P36423; -.
DR PaxDb; P36423; -.
DR PRIDE; P36423; -.
DR ProteomicsDB; 262808; -.
DR Antibodypedia; 18246; 474 antibodies from 33 providers.
DR DNASU; 21391; -.
DR Ensembl; ENSMUST00000003017; ENSMUSP00000003017; ENSMUSG00000029925.
DR GeneID; 21391; -.
DR KEGG; mmu:21391; -.
DR UCSC; uc009bld.1; mouse.
DR CTD; 6916; -.
DR MGI; MGI:98497; Tbxas1.
DR VEuPathDB; HostDB:ENSMUSG00000029925; -.
DR eggNOG; KOG0158; Eukaryota.
DR GeneTree; ENSGT00940000157903; -.
DR HOGENOM; CLU_001570_5_2_1; -.
DR InParanoid; P36423; -.
DR OMA; WPHPETF; -.
DR OrthoDB; 786853at2759; -.
DR PhylomeDB; P36423; -.
DR TreeFam; TF105087; -.
DR Reactome; R-MMU-211979; Eicosanoids.
DR Reactome; R-MMU-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR BioGRID-ORCS; 21391; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Tbxas1; mouse.
DR PRO; PR:P36423; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P36423; protein.
DR Bgee; ENSMUSG00000029925; Expressed in granulocyte and 117 other tissues.
DR ExpressionAtlas; P36423; baseline and differential.
DR Genevisible; P36423; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; ISO:MGI.
DR GO; GO:0006690; P:icosanoid metabolic process; ISS:UniProtKB.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
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; 1.
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..533
FT /note="Thromboxane-A synthase"
FT /id="PRO_0000052257"
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..335
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P24557"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 357..533
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P24557"
FT BINDING 479
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"
FT CONFLICT 77..87
FT /note="LCGYYLGRRMH -> SVWVLSWPSID (in Ref. 3; AAB87704)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 60391 MW; A06C3B53738E179A CRC64;
MEVLGLLKFE VSGTIVTVTL LVALLALLKW YSMSAFSRLE KLGIRHPKPS PFVGNLMFFR
QGFWESQLEL RERYGPLCGY YLGRRMHVVI SEPDMIKQVL VENFSNFSNR MASGLEPKMV
ADSVLLLRDR RWEEVRGALM SSFSPEKLDE MTPLISQACE LLVAHLKRYA ASRDAFNIQR
CYCCYTIDVV ASVAFGTQVD SQNSPEDPFV QHCRRASTFC IPRPLLVLIL SFPSIMVPLA
RILPNKNRDE LNGFFNTLIR NVIALRDQQA AEERRRDFLQ MVLDAQHSMN SVGVEGFDMV
PESLSSSECT KEPPQRCHPT STSKPFTVDE IVGQAFLFLI AGHEVITNTL SFITYLLATH
PDCQERLLKE VDLFMGKHPA PEYHSLQEGL PYLDMVISET LRMYPPAFRF TREAAQDCEV
LGQRIPAGTV LEIAVGALHH DPEHWPNPET FDPERFTAEA RLQRRPFTYL PFGAGPRSCL
GVRLGLLVVK LTILQVLHKF RFEASPETQV PLQLESKSAL GPKNGVYIKI VSR
