THAS_RAT
ID THAS_RAT Reviewed; 533 AA.
AC P49430;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Thromboxane-A synthase;
DE Short=TXA synthase;
DE Short=TXS;
DE EC=5.3.99.5 {ECO:0000250|UniProtKB:P24557};
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=8131852; DOI=10.1016/0014-5793(94)80146-0;
RA Tone Y., Miyata A., Hara S., Yukawa S., Tanabe T.;
RT "Abundant expression of thromboxane synthase in rat macrophages.";
RL FEBS Lett. 340:241-244(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=9261862; DOI=10.1016/s0090-6980(97)00059-2;
RA Tsutsumi E., Takeuchi K., Abe T., Takahashi N., Kato T., Taniyama Y.,
RA Ikeda Y., Ito S., Abe K.;
RT "Rat kidney thromboxane synthase: cDNA cloning and gene expression
RT regulation in hydronephrotic kidney.";
RL Prostaglandins 53:423-431(1997).
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:0000250|UniProtKB:P24557};
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 in bone marrow, spleen, lung, thymus,
CC liver, uterus, and macrophages. {ECO:0000269|PubMed:8131852,
CC ECO:0000269|PubMed:9261862}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; D28773; BAA05962.1; -; mRNA.
DR EMBL; D31798; BAA22574.1; -; mRNA.
DR PIR; S42404; S42404.
DR RefSeq; NP_036819.1; NM_012687.1.
DR AlphaFoldDB; P49430; -.
DR SMR; P49430; -.
DR STRING; 10116.ENSRNOP00000010796; -.
DR BindingDB; P49430; -.
DR ChEMBL; CHEMBL4028; -.
DR DrugCentral; P49430; -.
DR jPOST; P49430; -.
DR PaxDb; P49430; -.
DR PRIDE; P49430; -.
DR Ensembl; ENSRNOT00000010796; ENSRNOP00000010796; ENSRNOG00000007918.
DR GeneID; 24886; -.
DR KEGG; rno:24886; -.
DR UCSC; RGD:3826; rat.
DR CTD; 6916; -.
DR RGD; 3826; Tbxas1.
DR eggNOG; KOG0158; Eukaryota.
DR GeneTree; ENSGT00940000157903; -.
DR HOGENOM; CLU_001570_5_2_1; -.
DR InParanoid; P49430; -.
DR OMA; WPHPETF; -.
DR OrthoDB; 786853at2759; -.
DR PhylomeDB; P49430; -.
DR TreeFam; TF105087; -.
DR Reactome; R-RNO-211979; Eicosanoids.
DR Reactome; R-RNO-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR PRO; PR:P49430; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000007918; Expressed in colon and 19 other tissues.
DR Genevisible; P49430; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
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; ISO:RGD.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IMP:RGD.
DR GO; GO:0006690; P:icosanoid metabolic process; ISS:UniProtKB.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
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 2: Evidence at transcript 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_0000052259"
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"
SQ SEQUENCE 533 AA; 59974 MW; 6661BC5378D4E8C9 CRC64;
MEVLGLLKFE VSGTVVTVTL SVVLLALLKW YSTSAFSRLR KLGIRHPEPS PFVGNLMFFR
QGFWESHLEL RERYGPLCGY YLGRRMYIVI SDPDMIKEVL VENFSNFSNR MASGLEPKLI
ADSVLMLRDR RWEEVRGALM SAFSPEKLNE MTPLISQACE LLLSHLKHSA ASGDAFDIQR
CYCCFTTNVV ASVAFGIEVN SQDAPEDPFV QHCQRVFAFS TPRPLLALIL SFPSIMVPLA
RILPNKNRDE LNGFFNTLIR NVIALRDKQT AEERRGDFLQ MVLDAQRSMS SVGVEAFDMV
TEALSSAECM GDPPQRCHPT STAKPLTVDE IAGQAFLFLI AGHEITTNTL SFITYLLATH
PECQERLLKE VDLFMEKHPA PEYCNLQEGL PYLDMVVAET LRMYPPAFRF TREAAQDCEV
LGQHIPAGSV LEIAVGALHH DPEHWPNPET FDPERFTAEA RLQQKPFTYL PFGAGPRSCL
GVRLGLLVVK LTLLQVLHKF RFEACPETQV PLQLESKSAL CPKNGVYVKI VSR
