THAS_MACFA
ID THAS_MACFA Reviewed; 533 AA.
AC Q2PG45;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 77.
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 {ECO:0000250|UniProtKB:P24557};
DE EC=4.2.1.152 {ECO:0000250|UniProtKB:P24557};
GN Name=TBXAS1; Synonyms=CYP5, CYP5A1; ORFNames=QccE-11311;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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 -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 is the initiator. An alternative
CC upstream Met is found in primates, but not in other mammalians.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE72925.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB220392; BAE72925.1; ALT_INIT; mRNA.
DR RefSeq; NP_001271608.1; NM_001284679.1.
DR AlphaFoldDB; Q2PG45; -.
DR SMR; Q2PG45; -.
DR STRING; 9541.XP_005550979.1; -.
DR GeneID; 102128548; -.
DR CTD; 6916; -.
DR eggNOG; KOG0158; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
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; IEA:UniProtKB-EC.
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; 1.
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_0000380715"
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; 60447 MW; E21709EFB0B005F7 CRC64;
MEALGFLKLE VNGPMVTVAL SVALLALLKW YSTSAFSRLE KLGLRHPKPS PFIGNLMFFR
QGFWESQMEL RKLYGPLCGY YLGRRMFIVI SEPDMIKQVL VENFSNFTNR MASGLEFKSV
ADSVLFLRDK RWEEVRGALM SAFSPEKLNE MTPLISQACD LLLAHLKRYA ESGDAFDIQR
CYRNYTTDVV ASVAFGTPVD SQQAPEDPFV KHCKRFFEFC IPRPILVLLL SFPSIMVPLA
RILPNKNRDE LNGFFNKLIR NVIALRDQQA AEERRRDFLQ MVLDARHSAS PVGVQDFDMV
GDVFSSTRCK PNPSRQHQAG PMARPLTVDE IVGQAFIFLI AGYEIVTNTL SFATYLLATN
PDCQEKLLRE VDLFKEKHMV PEFCSLEEGL PYLDMVIAET LRMYPPAFRF TREAAQDCEV
LGQRIPAGAV LEMAVGALHH DPEHWPSPET FNPERFTAEA QQQHRPFTYL PFGAGPRSCL
GVRLGLLEVK LTLLHVLHKF QFQACPETQV PLQLESKSAL GPKNGVYIKI VSR
