THAS_HUMAN
ID THAS_HUMAN Reviewed; 533 AA.
AC P24557; B4DJG6; E7EMU9; E7EP08; E7ESB5; O14987; Q16843; Q16844; Q8IUN1;
AC Q96CN2; Q9GZW4; Q9HD77; Q9HD78; Q9HD79; Q9HD80; Q9HD81; Q9HD82; Q9HD83;
AC Q9HD84;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 3.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Thromboxane-A synthase;
DE Short=TXA synthase;
DE Short=TXS {ECO:0000303|PubMed:8366093};
DE EC=5.3.99.5 {ECO:0000269|PubMed:11097184, ECO:0000269|PubMed:11297515, ECO:0000269|PubMed:22735388, ECO:0000269|PubMed:24009185, ECO:0000269|PubMed:8436233, ECO:0000269|PubMed:9873013};
DE AltName: Full=Cytochrome P450 5A1;
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase {ECO:0000305};
DE EC=4.2.1.152 {ECO:0000269|PubMed:17459323};
GN Name=TBXAS1; Synonyms=CYP5, CYP5A1 {ECO:0000303|PubMed:11465543}, TXAS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Platelet;
RX PubMed=1714723; DOI=10.1016/0006-291x(91)91060-p;
RA Yokoyama C., Miyata A., Ihara H., Ullrich V., Tanabe T.;
RT "Molecular cloning of human platelet thromboxane A synthase.";
RL Biochem. Biophys. Res. Commun. 178:1479-1484(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Lung;
RX PubMed=1730669; DOI=10.1016/s0021-9258(18)48353-6;
RA Ohashi K., Ruan K.H., Kulmacz R.J., Wu K.K., Wang L.-H.;
RT "Primary structure of human thromboxane synthase determined from the cDNA
RT sequence.";
RL J. Biol. Chem. 267:789-793(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood;
RX PubMed=7925341; DOI=10.1111/j.1432-1033.1994.00273.x;
RA Miyata A., Yokoyama C., Ihara H., Bandoh S., Takeda O., Takahashi E.,
RA Tanabe T.;
RT "Characterization of the human gene (TBXAS1) encoding thromboxane
RT synthase.";
RL Eur. J. Biochem. 224:273-279(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Shen R.-F.;
RT "Human thromboxane A2 synthase.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-60; GLU-160; SER-245;
RP VAL-356; GLU-416; LYS-449; ASN-450 AND GLN-465.
RX PubMed=11465543; DOI=10.1016/s1383-5726(00)00004-2;
RA Chevalier D., Lo-Guidice J.-M., Sergent E., Allorge D., Debuysere H.,
RA Ferrari N., Libersa C., Lhermitte M., Broly F.;
RT "Identification of genetic variants in the human thromboxane synthase gene
RT (CYP5A1).";
RL Mutat. Res. 432:61-67(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-244 (ISOFORM 1/2).
RC TISSUE=Lung;
RX PubMed=2043115; DOI=10.1016/0006-291x(91)91980-q;
RA Wang L.-H., Oshashi K., Wu K.K.;
RT "Isolation of partial complementary DNA encoding human thromboxane
RT synthase.";
RL Biochem. Biophys. Res. Commun. 177:286-291(1991).
RN [11]
RP PRELIMINARY PROTEIN SEQUENCE OF 1-26; 96-110 AND 237-280.
RX PubMed=2195994; DOI=10.1016/0003-9861(90)90337-x;
RA Nuesing R., Schneider-Voss S., Ullrich V.;
RT "Immunoaffinity purification of human thromboxane synthase.";
RL Arch. Biochem. Biophys. 280:325-330(1990).
RN [12]
RP PARTIAL PROTEIN SEQUENCE.
RA Nuesing R.;
RL Thesis (1990), University of Konstanz, Germany.
RN [13]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=8436233; DOI=10.1016/0014-5793(93)81335-w;
RA Yokoyama C., Miyata A., Suzuki K., Nishikawa Y., Yoshimoto T., Yamamoto S.,
RA Nuesing R., Ullrich V., Tanabe T.;
RT "Expression of human thromboxane synthase using a baculovirus system.";
RL FEBS Lett. 318:91-94(1993).
RN [14]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=8366093; DOI=10.1016/s0021-9258(19)36541-x;
RA Ruan K.H., Wang L.-H., Wu K.K., Kulmacz R.J.;
RT "Amino-terminal topology of thromboxane synthase in the endoplasmic
RT reticulum.";
RL J. Biol. Chem. 268:19483-19490(1993).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=9873013; DOI=10.1074/jbc.274.2.762;
RA Hsu P.Y., Tsai A.L., Kulmacz R.J., Wang L.H.;
RT "Expression, purification, and spectroscopic characterization of human
RT thromboxane synthase.";
RL J. Biol. Chem. 274:762-769(1999).
RN [16]
RP INVOLVEMENT IN THROMBOXANE SYNTHETASE DEFICIENCY.
RX PubMed=6101498; DOI=10.1016/s0140-6736(80)90642-x;
RA Mestel F., Oetliker O., Beck E., Felix R., Imbach P., Wagner H.P.;
RT "Severe bleeding associated with defective thromboxane synthetase.";
RL Lancet 1:157-157(1980).
RN [17]
RP HEME-BINDING, MUTAGENESIS OF ASN-109; TRP-132; GLU-134; ARG-136; ARG-409;
RP ARG-412; ALA-414 AND ARG-477, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=11097184; DOI=10.1006/abbi.2000.2041;
RA Hsu P.Y., Tsai A.L., Wang L.H.;
RT "Identification of thromboxane synthase amino acid residues involved in
RT heme-propionate binding.";
RL Arch. Biochem. Biophys. 383:119-127(2000).
RN [18]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=11297515; DOI=10.1074/jbc.m009177200;
RA Wang L.H., Tsai A.L., Hsu P.Y.;
RT "Substrate binding is the rate-limiting step in thromboxane synthase
RT catalysis.";
RL J. Biol. Chem. 276:14737-14743(2001).
RN [19]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17459323; DOI=10.1016/j.abb.2007.03.012;
RA Yeh H.C., Tsai A.L., Wang L.H.;
RT "Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by
RT human prostacyclin and thromboxane synthases.";
RL Arch. Biochem. Biophys. 461:159-168(2007).
RN [20]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=24009185; DOI=10.1194/jlr.m037754;
RA Matsunobu T., Okuno T., Yokoyama C., Yokomizo T.;
RT "Thromboxane A synthase-independent production of 12-
RT hydroxyheptadecatrienoic acid, a BLT2 ligand.";
RL J. Lipid Res. 54:2979-2987(2013).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [23]
RP VARIANTS HIS-60; ILE-162; THR-331; VAL-356; GLU-416 AND THR-429.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [24]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [25]
RP VARIANTS GLU-160; VAL-356; GLU-416; CYS-424 AND THR-429.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
RN [26]
RP VARIANTS ILE-124; LYS-388; LYS-449 AND GLN-501.
RX PubMed=12721789; DOI=10.1007/s10038-003-0021-7;
RA Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C.,
RA Nakamura Y.;
RT "Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine
RT esterase genes, and two other genes in the Japanese population.";
RL J. Hum. Genet. 48:249-270(2003).
RN [27]
RP VARIANT [LARGE SCALE ANALYSIS] TRP-85.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [28]
RP VARIANTS GHDD PRO-82; GLN-412; TRP-481 AND PRO-487, INVOLVEMENT IN GHDD,
RP AND MUTAGENESIS OF CYS-479.
RX PubMed=18264100; DOI=10.1038/ng.2007.66;
RA Genevieve D., Proulle V., Isidor B., Bellais S., Serre V., Djouadi F.,
RA Picard C., Vignon-Savoye C., Bader-Meunier B., Blanche S.,
RA de Vernejoul M.-C., Legeai-Mallet L., Fischer A.-M., Le Merrer M.,
RA Dreyfus M., Gaussem P., Munnich A., Cormier-Daire V.;
RT "Thromboxane synthase mutations in an increased bone density disorder
RT (Ghosal syndrome).";
RL Nat. Genet. 40:284-286(2008).
RN [29]
RP CATALYTIC ACTIVITY, FUNCTION, CHARACTERIZATION OF VARIANTS GLU-257;
RP VAL-356; GLU-416; LYS-449 AND ASN-450, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22735388; DOI=10.1097/fpc.0b013e3283562d82;
RA Chen C.Y., Poole E.M., Ulrich C.M., Kulmacz R.J., Wang L.H.;
RT "Functional analysis of human thromboxane synthase polymorphic variants.";
RL Pharmacogenet. Genomics 22:653-658(2012).
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:8436233, PubMed:11297515,
CC PubMed:9873013, PubMed:11097184, PubMed:24009185, PubMed:22735388).
CC Cleaves also PGH2 to 12-hydroxy-heptadecatrienoicacid (12-HHT) and
CC malondialdehyde, which is known to act as a mediator of DNA damage. 12-
CC HHT and malondialdehyde are formed stoichiometrically in the same
CC amounts as TXA2 (PubMed:11297515, PubMed:9873013, PubMed:22735388).
CC Additionally, displays dehydratase activity, toward (15S)-hydroperoxy-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) producing 15-KETE and
CC 15-HETE (PubMed:17459323). {ECO:0000269|PubMed:11097184,
CC ECO:0000269|PubMed:11297515, ECO:0000269|PubMed:17459323,
CC ECO:0000269|PubMed:22735388, ECO:0000269|PubMed:24009185,
CC ECO:0000269|PubMed:8436233, ECO:0000269|PubMed:9873013}.
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:11097184, ECO:0000269|PubMed:11297515,
CC ECO:0000269|PubMed:22735388, ECO:0000269|PubMed:24009185,
CC ECO:0000269|PubMed:8436233, ECO:0000269|PubMed:9873013};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17138;
CC Evidence={ECO:0000305|PubMed:11297515, ECO:0000305|PubMed:8436233,
CC ECO:0000305|PubMed:9873013};
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:0000269|PubMed:11297515, ECO:0000269|PubMed:22735388,
CC ECO:0000269|PubMed:9873013};
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:0000269|PubMed:17459323};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55557;
CC Evidence={ECO:0000305|PubMed:17459323};
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:0000269|PubMed:17459323};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637;
CC Evidence={ECO:0000305|PubMed:17459323};
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:0000269|PubMed:17459323};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48857;
CC Evidence={ECO:0000305|PubMed:17459323};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:11097184};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=80 uM for 15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15-
CC HPETE) {ECO:0000269|PubMed:17459323};
CC KM=32 uM for prostaglandin H2 {ECO:0000269|PubMed:22735388};
CC KM=20 uM for prostaglandin H2 {ECO:0000269|PubMed:9873013};
CC Vmax=12 umol/min/mg enzyme for prostaglandin H2 as substrate
CC {ECO:0000269|PubMed:9873013};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000305}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:9873013}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:8366093}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P24557-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P24557-2; Sequence=VSP_047217;
CC Name=3;
CC IsoId=P24557-3; Sequence=VSP_054121;
CC Name=4;
CC IsoId=P24557-4; Sequence=VSP_054122, VSP_054123;
CC -!- TISSUE SPECIFICITY: Platelets, lung, kidney, spleen, macrophages and
CC lung fibroblasts. {ECO:0000269|PubMed:1714723,
CC ECO:0000269|PubMed:7925341}.
CC -!- DISEASE: Ghosal hematodiaphyseal dysplasia (GHDD) [MIM:231095]: Rare
CC autosomal recessive disorder characterized by increased bone density
CC with predominant diaphyseal involvement and aregenerative
CC corticosteroid-sensitive anemia. Aregenerative anemia is characterized
CC by bone marrow failure, so that functional marrow cells are regenerated
CC slowly or not at all. {ECO:0000269|PubMed:18264100}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Note=Thromboxane synthetase deficiency has been detected in
CC some patients with a bleeding disorder due to platelet dysfunction.
CC {ECO:0000269|PubMed:6101498}.
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 mammals.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60617.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA60618.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC01761.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAC01761.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99269.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99270.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99271.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99272.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99273.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99274.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99275.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99276.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99277.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99278.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF99279.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH41157.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG58828.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW83934.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP5A1 alleles;
CC URL="https://www.pharmvar.org/gene/TBXAS1";
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DR EMBL; M80646; AAA60617.1; ALT_INIT; mRNA.
DR EMBL; M80647; AAA60618.1; ALT_INIT; mRNA.
DR EMBL; D34625; BAA07011.1; -; Genomic_DNA.
DR EMBL; L36085; AAC01761.1; ALT_INIT; Genomic_DNA.
DR EMBL; L36075; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36076; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36077; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36078; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36079; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36080; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36081; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36082; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36083; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; L36084; AAC01761.1; JOINED; Genomic_DNA.
DR EMBL; AF233615; AAF99269.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233616; AAF99270.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233617; AAF99271.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233618; AAF99272.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233619; AAF99273.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233620; AAF99274.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233621; AAF99275.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233622; AAF99276.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233623; AAF99277.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233624; AAF99278.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF233625; AAF99279.1; ALT_INIT; Genomic_DNA.
DR EMBL; AK296069; BAG58828.1; ALT_INIT; mRNA.
DR EMBL; AC004914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004961; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006021; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471070; EAW83934.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC014117; AAH14117.1; -; mRNA.
DR EMBL; BC041157; AAH41157.1; ALT_INIT; mRNA.
DR EMBL; M74055; AAA36742.1; -; mRNA.
DR CCDS; CCDS55174.1; -. [P24557-3]
DR CCDS; CCDS55175.1; -. [P24557-2]
DR CCDS; CCDS5855.1; -. [P24557-1]
DR CCDS; CCDS5856.1; -. [P24557-4]
DR PIR; A41766; A41766.
DR PIR; S48161; S48161.
DR RefSeq; NP_001052.2; NM_001061.4. [P24557-1]
DR RefSeq; NP_001124438.1; NM_001130966.2. [P24557-1]
DR RefSeq; NP_001159725.1; NM_001166253.1. [P24557-3]
DR RefSeq; NP_001159726.1; NM_001166254.1. [P24557-2]
DR RefSeq; NP_112246.2; NM_030984.3. [P24557-4]
DR AlphaFoldDB; P24557; -.
DR SMR; P24557; -.
DR BioGRID; 112778; 6.
DR IntAct; P24557; 4.
DR MINT; P24557; -.
DR STRING; 9606.ENSP00000389414; -.
DR BindingDB; P24557; -.
DR ChEMBL; CHEMBL1835; -.
DR DrugBank; DB03052; Dazoxiben.
DR DrugBank; DB05505; NM-702.
DR DrugBank; DB01207; Ridogrel.
DR DrugBank; DB00795; Sulfasalazine.
DR DrugCentral; P24557; -.
DR GuidetoPHARMACOLOGY; 1353; -.
DR SwissLipids; SLP:000001099; -.
DR GlyGen; P24557; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P24557; -.
DR PhosphoSitePlus; P24557; -.
DR BioMuta; TBXAS1; -.
DR EPD; P24557; -.
DR jPOST; P24557; -.
DR MassIVE; P24557; -.
DR MaxQB; P24557; -.
DR PeptideAtlas; P24557; -.
DR PRIDE; P24557; -.
DR ProteomicsDB; 17017; -.
DR ProteomicsDB; 17264; -.
DR ProteomicsDB; 17954; -.
DR ProteomicsDB; 54216; -. [P24557-1]
DR Antibodypedia; 18246; 474 antibodies from 33 providers.
DR DNASU; 6916; -.
DR Ensembl; ENST00000336425.10; ENSP00000338087.7; ENSG00000059377.18. [P24557-1]
DR Ensembl; ENST00000411653.6; ENSP00000411326.3; ENSG00000059377.18. [P24557-4]
DR Ensembl; ENST00000425687.5; ENSP00000388736.1; ENSG00000059377.18. [P24557-2]
DR Ensembl; ENST00000448866.7; ENSP00000402536.3; ENSG00000059377.18. [P24557-1]
DR Ensembl; ENST00000458722.6; ENSP00000411274.3; ENSG00000059377.18. [P24557-3]
DR GeneID; 6916; -.
DR KEGG; hsa:6916; -.
DR MANE-Select; ENST00000448866.7; ENSP00000402536.3; NM_001061.7; NP_001052.3.
DR UCSC; uc010lne.4; human. [P24557-1]
DR CTD; 6916; -.
DR DisGeNET; 6916; -.
DR GeneCards; TBXAS1; -.
DR HGNC; HGNC:11609; TBXAS1.
DR HPA; ENSG00000059377; Tissue enhanced (lymphoid).
DR MalaCards; TBXAS1; -.
DR MIM; 231095; phenotype.
DR MIM; 274180; gene.
DR neXtProt; NX_P24557; -.
DR OpenTargets; ENSG00000059377; -.
DR Orphanet; 1802; Ghosal hematodiaphyseal dysplasia.
DR PharmGKB; PA349; -.
DR VEuPathDB; HostDB:ENSG00000059377; -.
DR eggNOG; KOG0158; Eukaryota.
DR GeneTree; ENSGT00940000157903; -.
DR HOGENOM; CLU_001570_5_2_1; -.
DR InParanoid; P24557; -.
DR OMA; WPHPETF; -.
DR OrthoDB; 750182at2759; -.
DR PhylomeDB; P24557; -.
DR TreeFam; TF105087; -.
DR BioCyc; MetaCyc:HS00728-MON; -.
DR PathwayCommons; P24557; -.
DR Reactome; R-HSA-211979; Eicosanoids.
DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR Reactome; R-HSA-5579032; Defective TBXAS1 causes GHDD.
DR SignaLink; P24557; -.
DR SIGNOR; P24557; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 6916; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; TBXAS1; human.
DR GeneWiki; Thromboxane-A_synthase; -.
DR GenomeRNAi; 6916; -.
DR Pharos; P24557; Tchem.
DR PRO; PR:P24557; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P24557; protein.
DR Bgee; ENSG00000059377; Expressed in monocyte and 109 other tissues.
DR ExpressionAtlas; P24557; baseline and differential.
DR Genevisible; P24557; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036134; F:12-hydroxyheptadecatrienoic acid synthase activity; TAS:Reactome.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0106256; F:hydroperoxy icosatetraenoate dehydratase activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IEA:Ensembl.
DR GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome.
DR GO; GO:0006690; P:icosanoid metabolic process; IDA:UniProtKB.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IMP: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; 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 Alternative splicing; Direct protein sequencing; Disease variant;
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_0000052256"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:8366093"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..75
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:8366093"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:8366093"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..335
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:8366093"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 357..533
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:8366093"
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 VAR_SEQ 1..67
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047217"
FT VAR_SEQ 150
FT /note="E -> ELGLLIMQERIKGHMGGQQAPQRIPPTRLSKPSGIYVNLHYATLPFC
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054121"
FT VAR_SEQ 456..459
FT /note="FTAE -> YRCS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:1730669"
FT /id="VSP_054122"
FT VAR_SEQ 460..533
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:1730669"
FT /id="VSP_054123"
FT VARIANT 60
FT /note="R -> H (in allele CYP5A1*2; dbSNP:rs6138)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:11465543"
FT /id="VAR_014157"
FT VARIANT 70
FT /note="L -> P (in dbSNP:rs13306050)"
FT /id="VAR_058465"
FT VARIANT 70
FT /note="L -> V (in dbSNP:rs4529)"
FT /id="VAR_058466"
FT VARIANT 82
FT /note="L -> P (in GHDD; dbSNP:rs140005285)"
FT /evidence="ECO:0000269|PubMed:18264100"
FT /id="VAR_044386"
FT VARIANT 85
FT /note="R -> W (in a breast cancer sample; somatic mutation;
FT dbSNP:rs1016604233)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036294"
FT VARIANT 124
FT /note="V -> I (in dbSNP:rs8192833)"
FT /evidence="ECO:0000269|PubMed:12721789"
FT /id="VAR_018378"
FT VARIANT 160
FT /note="D -> E (in allele CYP5A1*3; dbSNP:rs5768)"
FT /evidence="ECO:0000269|PubMed:10391210,
FT ECO:0000269|PubMed:11465543"
FT /id="VAR_010919"
FT VARIANT 162
FT /note="L -> I (in dbSNP:rs6137)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014158"
FT VARIANT 245
FT /note="N -> S (in allele CYP5A1*4; dbSNP:rs55856189)"
FT /evidence="ECO:0000269|PubMed:11465543"
FT /id="VAR_010920"
FT VARIANT 257
FT /note="K -> E (the KM value is about 1.5 higher for PEG2;
FT in allele CYP5A1*5; KM value about 1.5 higher for PEG2;
FT Vmax/KM approximately 50% of that of the wild-type;
FT dbSNP:rs5769)"
FT /evidence="ECO:0000269|PubMed:22735388"
FT /id="VAR_014647"
FT VARIANT 260
FT /note="R -> G (in dbSNP:rs5770)"
FT /id="VAR_014648"
FT VARIANT 316
FT /note="Q -> K (in dbSNP:rs5771)"
FT /id="VAR_014649"
FT VARIANT 331
FT /note="I -> T (in dbSNP:rs6140)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014159"
FT VARIANT 356
FT /note="L -> V (in allele CYP5A1*5; KM value about 1.5
FT higher for PEG2; Vmax/KM approximately 27% of that of the
FT wild-type; dbSNP:rs4529)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:11465543,
FT ECO:0000269|PubMed:22735388"
FT /id="VAR_010921"
FT VARIANT 357
FT /note="L -> V (in dbSNP:rs4529)"
FT /id="VAR_044387"
FT VARIANT 387
FT /note="E -> K (in dbSNP:rs3735354)"
FT /id="VAR_055565"
FT VARIANT 388
FT /note="E -> K (in dbSNP:rs3735354)"
FT /evidence="ECO:0000269|PubMed:12721789"
FT /id="VAR_018379"
FT VARIANT 389
FT /note="G -> V (in dbSNP:rs5760)"
FT /id="VAR_016158"
FT VARIANT 412
FT /note="R -> Q (in GHDD; dbSNP:rs199422117)"
FT /evidence="ECO:0000269|PubMed:18264100"
FT /id="VAR_044388"
FT VARIANT 416
FT /note="Q -> E (in allele CYP5A1*6; does not affect KM value
FT for PEG2; does not affect Vmax/KM value; dbSNP:rs4528)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:11465543,
FT ECO:0000269|PubMed:22735388"
FT /id="VAR_010922"
FT VARIANT 424
FT /note="R -> C (in dbSNP:rs5762)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014160"
FT VARIANT 429
FT /note="A -> T (in dbSNP:rs4526)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210"
FT /id="VAR_014161"
FT VARIANT 449
FT /note="E -> K (in allele CYP5A1*7; does not affect KM value
FT for PEG2; does not affect Vmax/KM value; dbSNP:rs8192868)"
FT /evidence="ECO:0000269|PubMed:11465543,
FT ECO:0000269|PubMed:12721789, ECO:0000269|PubMed:22735388"
FT /id="VAR_010923"
FT VARIANT 450
FT /note="T -> N (in allele CYP5A1*8; KM value about 1.5
FT higher for PEG2; Vmax/KM approximately 56 % of that of the
FT wild-type; dbSNP:rs5763)"
FT /evidence="ECO:0000269|PubMed:11465543,
FT ECO:0000269|PubMed:22735388"
FT /id="VAR_010924"
FT VARIANT 465
FT /note="R -> Q (in allele CYP5A1*9; dbSNP:rs41311778)"
FT /evidence="ECO:0000269|PubMed:11465543"
FT /id="VAR_010925"
FT VARIANT 481
FT /note="G -> W (in GHDD; dbSNP:rs199422116)"
FT /evidence="ECO:0000269|PubMed:18264100"
FT /id="VAR_044389"
FT VARIANT 487
FT /note="L -> P (in GHDD; dbSNP:rs199422114)"
FT /evidence="ECO:0000269|PubMed:18264100"
FT /id="VAR_044390"
FT VARIANT 501
FT /note="R -> Q (in dbSNP:rs8192864)"
FT /evidence="ECO:0000269|PubMed:12721789"
FT /id="VAR_018380"
FT VARIANT 511
FT /note="P -> L (in dbSNP:rs13306050)"
FT /id="VAR_055566"
FT VARIANT 512
FT /note="L -> P (in dbSNP:rs13306050)"
FT /id="VAR_044391"
FT MUTAGEN 109
FT /note="N->I: Loss of thromboxane-A synthase activity.
FT Decreased heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 132
FT /note="W->F: Loss of thromboxane-A synthase activity.
FT Decreased heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 134
FT /note="E->D: Does not affect thromboxane-A synthase
FT activity. Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 136
FT /note="R->A,K: Loss of thromboxane-A synthase activity.
FT Decreased heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 409
FT /note="R->G: Does not affect thromboxane-A synthase
FT activity. Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 412
FT /note="R->K: Loss of thromboxane-A synthase activity.
FT Decreased heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 414
FT /note="A->V: Does not affect thromboxane-A synthase
FT activity. Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 477
FT /note="R->A: Loss of thromboxane-A synthase activity.
FT Decreased heme-binding."
FT /evidence="ECO:0000269|PubMed:11097184"
FT MUTAGEN 479
FT /note="C->S,H,Y: Loss of thromboxane-A synthase activity.
FT Decreased heme-binding."
FT /evidence="ECO:0000269|PubMed:18264100"
FT CONFLICT 102
FT /note="E -> Q (in Ref. 10; AAA36742)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="L -> V (in Ref. 4; AAC01761)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="A -> P (in Ref. 2; AAA60617/AAA60618, 4; AAC01761,
FT 5; AAF99269/AAF99270/AAF99271/AAF99272/AAF99273/AAF99274/
FT AAF99275/AAF99276/AAF99277/AAF99278/AAF99279 and 10;
FT AAA36742)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="S -> G (in Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 483
FT /note="R -> H (in Ref. 3; BAA07011)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 60518 MW; E95E7B7EA77E6DDC CRC64;
MEALGFLKLE VNGPMVTVAL SVALLALLKW YSTSAFSRLE KLGLRHPKPS PFIGNLTFFR
QGFWESQMEL RKLYGPLCGY YLGRRMFIVI SEPDMIKQVL VENFSNFTNR MASGLEFKSV
ADSVLFLRDK RWEEVRGALM SAFSPEKLNE MVPLISQACD LLLAHLKRYA ESGDAFDIQR
CYCNYTTDVV ASVAFGTPVD SWQAPEDPFV KHCKRFFEFC IPRPILVLLL SFPSIMVPLA
RILPNKNRDE LNGFFNKLIR NVIALRDQQA AEERRRDFLQ MVLDARHSAS PMGVQDFDIV
RDVFSSTGCK PNPSRQHQPS PMARPLTVDE IVGQAFIFLI AGYEIITNTL SFATYLLATN
PDCQEKLLRE VDVFKEKHMA PEFCSLEEGL PYLDMVIAET LRMYPPAFRF TREAAQDCEV
LGQRIPAGAV LEMAVGALHH DPEHWPSPET FNPERFTAEA RQQHRPFTYL PFGAGPRSCL
GVRLGLLEVK LTLLHVLHKF RFQACPETQV PLQLESKSAL GPKNGVYIKI VSR
