PGH2_HUMAN
ID PGH2_HUMAN Reviewed; 604 AA.
AC P35354; A8K802; Q16876;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Prostaglandin G/H synthase 2 {ECO:0000305};
DE EC=1.14.99.1 {ECO:0000269|PubMed:16373578, ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593};
DE AltName: Full=Cyclooxygenase-2 {ECO:0000303|PubMed:17113084};
DE Short=COX-2 {ECO:0000303|PubMed:17113084};
DE AltName: Full=PHS II;
DE AltName: Full=Prostaglandin H2 synthase 2;
DE Short=PGH synthase 2;
DE Short=PGHS-2;
DE AltName: Full=Prostaglandin-endoperoxide synthase 2;
DE Flags: Precursor;
GN Name=PTGS2 {ECO:0000312|HGNC:HGNC:9605};
GN Synonyms=COX2 {ECO:0000303|PubMed:17113084};
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].
RC TISSUE=Endothelial cell;
RX PubMed=8473346; DOI=10.1016/s0021-9258(18)52976-8;
RA Jones D.A., Carlton D.P., McIntyre T.M., Zimmerman G.A., Prescott S.M.;
RT "Molecular cloning of human prostaglandin endoperoxide synthase type II and
RT demonstration of expression in response to cytokines.";
RL J. Biol. Chem. 268:9049-9054(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Endothelial cell;
RX PubMed=1380156; DOI=10.1073/pnas.89.16.7384;
RA Hla T., Neilson K.;
RT "Human cyclooxygenase-2 cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7384-7388(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Peripheral blood;
RX PubMed=8181472; DOI=10.1111/j.1432-1033.1994.tb18804.x;
RA Kosaka T., Miyata A., Ihara H., Hara S., Sugimoto T., Takeda O.,
RA Takahashi E., Tanabe T.;
RT "Characterization of the human gene (PTGS2) encoding prostaglandin-
RT endoperoxide synthase 2.";
RL Eur. J. Biochem. 221:889-897(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7945196; DOI=10.1042/bj3020723;
RA Appleby S.B., Ristimaki A., Neilson K., Narko K., Hla T.;
RT "Structure of the human cyclo-oxygenase-2 gene.";
RL Biochem. J. 302:723-727(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RA Sharma S.V., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-228; ALA-428; ALA-511
RP AND ARG-587.
RG NIEHS SNPs program;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovium;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [12]
RP CHARACTERIZATION, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=7947975; DOI=10.1016/0167-4838(94)90148-1;
RA Barnett J., Chow J., Ives D., Chiou M., Mackenzie R., Osen E., Nguyen B.,
RA Tsing S., Bach C., Freire J.;
RT "Purification, characterization and selective inhibition of human
RT prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system.";
RL Biochim. Biophys. Acta 1209:130-139(1994).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=7592599; DOI=10.1074/jbc.270.41.24019;
RA Kulmacz R.J., Wang L.H.;
RT "Comparison of hydroperoxide initiator requirements for the cyclooxygenase
RT activities of prostaglandin H synthase-1 and -2.";
RL J. Biol. Chem. 270:24019-24023(1995).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=9048568; DOI=10.1021/bi962476u;
RA Xiao G., Tsai A.L., Palmer G., Boyar W.C., Marshall P.J., Kulmacz R.J.;
RT "Analysis of hydroperoxide-induced tyrosyl radicals and lipoxygenase
RT activity in aspirin-treated human prostaglandin H synthase-2.";
RL Biochemistry 36:1836-1845(1997).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLN-189 AND HIS-193.
RX PubMed=9261177; DOI=10.1074/jbc.272.34.21565;
RA Landino L.M., Crews B.C., Gierse J.K., Hauser S.D., Marnett L.J.;
RT "Mutational analysis of the role of the distal histidine and glutamine
RT residues of prostaglandin-endoperoxide synthase-2 in peroxidase catalysis,
RT hydroperoxide reduction, and cyclooxygenase activation.";
RL J. Biol. Chem. 272:21565-21574(1997).
RN [16]
RP SUBCELLULAR LOCATION, AND INDUCTION BY IL1B AND LIPOPOLYSACCHARIDE.
RX PubMed=9545330; DOI=10.1074/jbc.273.16.9886;
RA Spencer A.G., Woods J.W., Arakawa T., Singer I.I., Smith W.L.;
RT "Subcellular localization of prostaglandin endoperoxide H synthases-1 and
RT -2 by immunoelectron microscopy.";
RL J. Biol. Chem. 273:9886-9893(1998).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=11034610; DOI=10.1084/jem.192.8.1197;
RA Serhan C.N., Clish C.B., Brannon J., Colgan S.P., Chiang N., Gronert K.;
RT "Novel functional sets of lipid-derived mediators with antiinflammatory
RT actions generated from omega-3 fatty acids via cyclooxygenase 2-
RT nonsteroidal antiinflammatory drugs and transcellular processing.";
RL J. Exp. Med. 192:1197-1204(2000).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=11192938;
RA Serhan C.N., Clish C.B., Brannon J., Colgan S.P., Gronert K., Chiang N.;
RT "Anti-microinflammatory lipid signals generated from dietary N-3 fatty
RT acids via cyclooxygenase-2 and transcellular processing: a novel mechanism
RT for NSAID and N-3 PUFA therapeutic actions.";
RL J. Physiol. Pharmacol. 51:643-654(2000).
RN [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11939906; DOI=10.1042/bj20011798;
RA Levin G., Duffin K.L., Obukowicz M.G., Hummert S.L., Fujiwara H.,
RA Needleman P., Raz A.;
RT "Differential metabolism of dihomo-gamma-linolenic acid and arachidonic
RT acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular
RT synthesis of prostaglandin E1 and prostaglandin E2.";
RL Biochem. J. 365:489-496(2002).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=12391014; DOI=10.1084/jem.20020760;
RA Serhan C.N., Hong S., Gronert K., Colgan S.P., Devchand P.R., Mirick G.,
RA Moussignac R.L.;
RT "Resolvins: a family of bioactive products of omega-3 fatty acid
RT transformation circuits initiated by aspirin treatment that counter
RT proinflammation signals.";
RL J. Exp. Med. 196:1025-1037(2002).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP S-NITROSYLATION AT CYS-526, AND MUTAGENESIS OF CYS-526; CYS-555 AND
RP CYS-561.
RX PubMed=16373578; DOI=10.1126/science.1119407;
RA Kim S.F., Huri D.A., Snyder S.H.;
RT "Inducible nitric oxide synthase binds, S-nitrosylates, and activates
RT cyclooxygenase-2.";
RL Science 310:1966-1970(2005).
RN [22]
RP GLYCOSYLATION AT ASN-580.
RX PubMed=17113084; DOI=10.1016/j.febslet.2006.10.073;
RA Sevigny M.B., Li C.F., Alas M., Hughes-Fulford M.;
RT "Glycosylation regulates turnover of cyclooxygenase-2.";
RL FEBS Lett. 580:6533-6536(2006).
RN [23]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=21206090; DOI=10.1172/jci42545;
RA Oh S.F., Pillai P.S., Recchiuti A., Yang R., Serhan C.N.;
RT "Pro-resolving actions and stereoselective biosynthesis of 18S E-series
RT resolvins in human leukocytes and murine inflammation.";
RL J. Clin. Invest. 121:569-581(2011).
RN [24]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22942274; DOI=10.1074/jbc.m112.381202;
RA Musee J., Marnett L.J.;
RT "Prostaglandin H synthase-2-catalyzed oxygenation of 2-arachidonoylglycerol
RT is more sensitive to peroxide tone than oxygenation of arachidonic acid.";
RL J. Biol. Chem. 287:37383-37394(2012).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=22068350; DOI=10.1194/jlr.m017822;
RA Tejera N., Boeglin W.E., Suzuki T., Schneider C.;
RT "COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic
RT acids in activated human leukocytes.";
RL J. Lipid Res. 53:87-94(2012).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION BY IL1B.
RX PubMed=26282205; DOI=10.1016/j.bbrc.2015.08.054;
RA Kuwata H., Hara S.;
RT "Inhibition of long-chain acyl-CoA synthetase 4 facilitates production of
RT 5, 11-dihydroxyeicosatetraenoic acid via the cyclooxygenase-2 pathway.";
RL Biochem. Biophys. Res. Commun. 465:528-533(2015).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=26236990; DOI=10.1038/nm.3911;
RA Dalli J., Chiang N., Serhan C.N.;
RT "Elucidation of novel 13-series resolvins that increase with atorvastatin
RT and clear infections.";
RL Nat. Med. 21:1071-1075(2015).
RN [28]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=27642067; DOI=10.1016/j.chembiol.2016.08.009;
RA Liu X., Moon S.H., Jenkins C.M., Sims H.F., Gross R.W.;
RT "Cyclooxygenase-2 Mediated Oxidation of 2-Arachidonoyl-Lysophospholipids
RT Identifies Unknown Lipid Signaling Pathways.";
RL Cell Chem. Biol. 23:1217-1227(2016).
RN [29]
RP REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
RX PubMed=10966456; DOI=10.1146/annurev.biochem.69.1.145;
RA Smith W.L., DeWitt D.L., Garavito R.M.;
RT "Cyclooxygenases: structural, cellular, and molecular biology.";
RL Annu. Rev. Biochem. 69:145-182(2000).
RN [30]
RP REVIEW ON FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19540099; DOI=10.1016/j.plefa.2009.05.020;
RA Le H.D., Meisel J.A., de Meijer V.E., Gura K.M., Puder M.;
RT "The essentiality of arachidonic acid and docosahexaenoic acid.";
RL Prostaglandins Leukot. Essent. Fatty Acids 81:165-170(2009).
RN [31]
RP REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL
RP CANCER.
RX PubMed=24605250; DOI=10.4292/wjgpt.v5.i1.40;
RA Sostres C., Gargallo C.J., Lanas A.;
RT "Aspirin, cyclooxygenase inhibition and colorectal cancer.";
RL World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014).
RN [32] {ECO:0007744|PDB:5KIR}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 19-569 IN COMPLEX WITH
RP PROTOPORPHYRIN IX AND ROFECOXIB, COFACTOR, GLYCOSYLATION AT ASN-130 AND
RP ASN-396, AND DISULFIDE BONDS.
RX PubMed=27710942; DOI=10.1107/s2053230x16014230;
RA Orlando B.J., Malkowski M.G.;
RT "Crystal structure of rofecoxib bound to human cyclooxygenase-2.";
RL Acta Crystallogr. F 72:772-776(2016).
RN [33] {ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A}
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 19-569 IN COMPLEX WITH
RP PROTOPORPHYRIN IX AND SALICYLIC ACID, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, MUTAGENESIS OF SER-516
RP AND GLY-519, ACTIVITY REGULATION, GLYCOSYLATION AT ASN-53; ASN-130 AND
RP ASN-396, AND DISULFIDE BONDS.
RX PubMed=26859324; DOI=10.1021/acs.biochem.5b01378;
RA Lucido M.J., Orlando B.J., Vecchio A.J., Malkowski M.G.;
RT "Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight
RT into the Formation of Products with Reversed Stereochemistry.";
RL Biochemistry 55:1226-1238(2016).
RN [34] {ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR, ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV}
RP X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) OF 19-569 IN COMPLEX WITH
RP PROTOPORPHYRIN IX AND FLUFENAMIC ACID, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, COFACTOR, SUBUNIT, GLYCOSYLATION AT ASN-53; ASN-130
RP AND ASN-396, DISULFIDE BONDS, AND MUTAGENESIS OF TYR-371 AND SER-516.
RX PubMed=27226593; DOI=10.1074/jbc.m116.725713;
RA Orlando B.J., Malkowski M.G.;
RT "Substrate-selective Inhibition of Cyclooxygeanse-2 by Fenamic Acid
RT Derivatives Is Dependent on Peroxide Tone.";
RL J. Biol. Chem. 291:15069-15081(2016).
RN [35]
RP VARIANT ALA-511.
RX PubMed=15308583; DOI=10.1093/carcin/bgh260;
RA Goodman J.E., Bowman E.D., Chanock S.J., Alberg A.J., Harris C.C.;
RT "Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms
RT and colon cancer risk.";
RL Carcinogenesis 25:2467-2472(2004).
CC -!- FUNCTION: Dual cyclooxygenase and peroxidase in the biosynthesis
CC pathway of prostanoids, a class of C20 oxylipins mainly derived from
CC arachidonate, with a particular role in the inflammatory response
CC (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578,
CC PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:11939906,
CC PubMed:19540099). The cyclooxygenase activity oxygenates arachidonate
CC (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2
CC (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy
CC endoperoxide PGH2, the precursor of all 2-series prostaglandins and
CC thromboxanes (PubMed:7947975, PubMed:7592599, PubMed:9261177,
CC PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593).
CC This complex transformation is initiated by abstraction of hydrogen at
CC carbon 13 (with S-stereochemistry), followed by insertion of molecular
CC O2 to form the endoperoxide bridge between carbon 9 and 11 that defines
CC prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase
CC activity) yields a hydroperoxy group in PGG2 that is then reduced to
CC PGH2 by two electrons (PubMed:7947975, PubMed:7592599, PubMed:9261177,
CC PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593).
CC Similarly catalyzes successive cyclooxygenation and peroxidation of
CC dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA,
CC C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-
CC series prostaglandins (PubMed:11939906, PubMed:19540099). In an
CC alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl
CC lysophopholipids to prostanoid lysophopholipids, which are then
CC hydrolyzed by intracellular phospholipases to release free prostanoids
CC (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the
CC glyceryl ester of PGH2, a process that can contribute to pain response
CC (PubMed:22942274). Generates lipid mediators from n-3 and n-6
CC polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism.
CC Oxygenates PUFAs to hydroperoxy compounds and then reduces them to
CC corresponding alcohols (PubMed:11034610, PubMed:11192938,
CC PubMed:9048568, PubMed:9261177). Plays a role in the generation of
CC resolution phase interaction products (resolvins) during both sterile
CC and infectious inflammation (PubMed:12391014). Metabolizes
CC docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-
CC series resolvins (RvDs) (PubMed:12391014). As a component of the
CC biosynthetic pathway of E-series resolvins (RvEs), converts
CC eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is
CC further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-
CC RvE2 (PubMed:21206090). In vascular endothelial cells, converts
CC docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-
CC series resolvins (RvTs) shown to activate macrophage phagocytosis
CC during bacterial infection (PubMed:26236990). In activated leukocytes,
CC contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to
CC diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350,
CC PubMed:26282205). During neuroinflammation, plays a role in neuronal
CC secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4
CC that regulates phagocytic microglia (By similarity).
CC {ECO:0000250|UniProtKB:Q05769, ECO:0000269|PubMed:11034610,
CC ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:11939906,
CC ECO:0000269|PubMed:12391014, ECO:0000269|PubMed:16373578,
CC ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:22068350,
CC ECO:0000269|PubMed:22942274, ECO:0000269|PubMed:26236990,
CC ECO:0000269|PubMed:26282205, ECO:0000269|PubMed:26859324,
CC ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27642067,
CC ECO:0000269|PubMed:7592599, ECO:0000269|PubMed:7947975,
CC ECO:0000269|PubMed:9048568, ECO:0000269|PubMed:9261177,
CC ECO:0000303|PubMed:19540099}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = A + H2O +
CC prostaglandin H2; Xref=Rhea:RHEA:23728, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57405; EC=1.14.99.1;
CC Evidence={ECO:0000269|PubMed:16373578, ECO:0000269|PubMed:22942274,
CC ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593,
CC ECO:0000269|PubMed:7592599, ECO:0000269|PubMed:7947975,
CC ECO:0000269|PubMed:9261177};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729;
CC Evidence={ECO:0000305|PubMed:16373578, ECO:0000305|PubMed:22942274,
CC ECO:0000305|PubMed:26859324, ECO:0000305|PubMed:27226593,
CC ECO:0000305|PubMed:7592599, ECO:0000305|PubMed:7947975,
CC ECO:0000305|PubMed:9261177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = prostaglandin G2;
CC Xref=Rhea:RHEA:42596, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:82629; Evidence={ECO:0000269|PubMed:22942274,
CC ECO:0000269|PubMed:7592599, ECO:0000269|PubMed:7947975,
CC ECO:0000269|PubMed:9261177};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597;
CC Evidence={ECO:0000305|PubMed:22942274, ECO:0000305|PubMed:7592599,
CC ECO:0000305|PubMed:7947975, ECO:0000305|PubMed:9261177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + prostaglandin G2 = A + H2O + prostaglandin H2;
CC Xref=Rhea:RHEA:42600, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57405, ChEBI:CHEBI:82629;
CC Evidence={ECO:0000269|PubMed:22942274, ECO:0000269|PubMed:7592599,
CC ECO:0000269|PubMed:7947975, ECO:0000269|PubMed:9261177};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601;
CC Evidence={ECO:0000305|PubMed:22942274, ECO:0000305|PubMed:7592599,
CC ECO:0000305|PubMed:7947975, ECO:0000305|PubMed:9261177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + 2 O2 = prostaglandin
CC G3; Xref=Rhea:RHEA:50444, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:133133; Evidence={ECO:0000303|PubMed:19540099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50445;
CC Evidence={ECO:0000303|PubMed:19540099};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + prostaglandin G3 = A + H2O + prostaglandin H3;
CC Xref=Rhea:RHEA:50448, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:133133, ChEBI:CHEBI:133134;
CC Evidence={ECO:0000303|PubMed:19540099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50449;
CC Evidence={ECO:0000303|PubMed:19540099};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienoate + 2 O2 = prostaglandin G1;
CC Xref=Rhea:RHEA:50424, ChEBI:CHEBI:15379, ChEBI:CHEBI:71589,
CC ChEBI:CHEBI:133084; Evidence={ECO:0000269|PubMed:11939906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50425;
CC Evidence={ECO:0000305|PubMed:11939906};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + prostaglandin G1 = A + H2O + prostaglandin H1;
CC Xref=Rhea:RHEA:50432, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:90793, ChEBI:CHEBI:133084;
CC Evidence={ECO:0000269|PubMed:11939906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50433;
CC Evidence={ECO:0000305|PubMed:11939906};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphoethanolamine + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-
CC phosphoethanolamine; Xref=Rhea:RHEA:54204, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:76091, ChEBI:CHEBI:138098;
CC Evidence={ECO:0000269|PubMed:27642067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54205;
CC Evidence={ECO:0000305|PubMed:27642067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(prostaglandin G2)-sn-glycero-3-phosphoethanolamine + AH2 =
CC 2-(prostaglandin H2)-sn-glycero-3-phosphoethanolamine + A + H2O;
CC Xref=Rhea:RHEA:54208, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:138098, ChEBI:CHEBI:138099;
CC Evidence={ECO:0000269|PubMed:27642067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54209;
CC Evidence={ECO:0000305|PubMed:27642067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:54212, ChEBI:CHEBI:15379, ChEBI:CHEBI:76079,
CC ChEBI:CHEBI:138100; Evidence={ECO:0000269|PubMed:27642067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54213;
CC Evidence={ECO:0000305|PubMed:27642067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(prostaglandin G2)-sn-glycero-3-phosphocholine + AH2 = 2-
CC (prostaglandin H2)-sn-glycero-3-phosphocholine + A + H2O;
CC Xref=Rhea:RHEA:54216, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:138100, ChEBI:CHEBI:138101;
CC Evidence={ECO:0000269|PubMed:27642067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54217;
CC Evidence={ECO:0000305|PubMed:27642067};
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:9261177};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48857;
CC Evidence={ECO:0000305|PubMed:9261177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC + AH2 + O2 = 2-[(15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-
CC glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53684,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137584;
CC Evidence={ECO:0000269|PubMed:27642067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53685;
CC Evidence={ECO:0000305|PubMed:27642067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC + AH2 + O2 = 2-[(15R)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-
CC glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53680,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137583;
CC Evidence={ECO:0000269|PubMed:27642067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53681;
CC Evidence={ECO:0000305|PubMed:27642067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC + AH2 + O2 = 2-[(11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoyl]-sn-
CC glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53676,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137582;
CC Evidence={ECO:0000269|PubMed:27642067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53677;
CC Evidence={ECO:0000305|PubMed:27642067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = 9-hydroxy-(10E,12Z)-
CC octadecadienoate + A + H2O; Xref=Rhea:RHEA:50864, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:133820;
CC Evidence={ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50865;
CC Evidence={ECO:0000305|PubMed:11034610, ECO:0000305|PubMed:11192938};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = 13-hydroxy-(9Z,11E)-
CC octadecadienoate + A + H2O; Xref=Rhea:RHEA:50860, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:133819;
CC Evidence={ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50861;
CC Evidence={ECO:0000305|PubMed:11034610, ECO:0000305|PubMed:11192938};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (15R)-hydroxy-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:50856,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:78837;
CC Evidence={ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50857;
CC Evidence={ECO:0000305|PubMed:11034610, ECO:0000305|PubMed:11192938};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (11R)-hydroxy-
CC (5Z,8Z,12E,14Z)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:50852,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:78836;
CC Evidence={ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50853;
CC Evidence={ECO:0000305|PubMed:11034610, ECO:0000305|PubMed:11192938};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (11R)-
CC hydroxy-(5Z,8Z,12E,14Z,17Z)-eicosapentaenoate + A + H2O;
CC Xref=Rhea:RHEA:50848, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:90820; Evidence={ECO:0000269|PubMed:11034610,
CC ECO:0000269|PubMed:11192938};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50849;
CC Evidence={ECO:0000305|PubMed:11034610, ECO:0000305|PubMed:11192938};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18S)-
CC hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2O;
CC Xref=Rhea:RHEA:50200, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:132083; Evidence={ECO:0000269|PubMed:21206090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50201;
CC Evidence={ECO:0000305|PubMed:21206090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18R)-
CC hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2O;
CC Xref=Rhea:RHEA:48836, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:90818; Evidence={ECO:0000269|PubMed:11034610,
CC ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:21206090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48837;
CC Evidence={ECO:0000305|PubMed:11034610, ECO:0000305|PubMed:11192938,
CC ECO:0000305|PubMed:21206090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15R)-
CC hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2O;
CC Xref=Rhea:RHEA:48840, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:90819; Evidence={ECO:0000269|PubMed:11034610,
CC ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:21206090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48841;
CC Evidence={ECO:0000305|PubMed:11034610, ECO:0000305|PubMed:11192938,
CC ECO:0000305|PubMed:21206090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15S)-
CC hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2O;
CC Xref=Rhea:RHEA:50196, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:132087; Evidence={ECO:0000269|PubMed:21206090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50197;
CC Evidence={ECO:0000305|PubMed:21206090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + AH2 + O2 = 13R-
CC hydroxy-(7Z,10Z,14E,16Z,19Z)-docosapentaenoate + A + H2O;
CC Xref=Rhea:RHEA:48852, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77224,
CC ChEBI:CHEBI:90824; Evidence={ECO:0000269|PubMed:26236990};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48853;
CC Evidence={ECO:0000305|PubMed:26236990};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 13-
CC hydroxy-(4Z,7Z,10Z,14E,16Z,19Z)-docosahexaenoate + A + H2O;
CC Xref=Rhea:RHEA:48820, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:90815; Evidence={ECO:0000269|PubMed:12391014};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48821;
CC Evidence={ECO:0000305|PubMed:12391014};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 =
CC (5S,15R)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O;
CC Xref=Rhea:RHEA:48812, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632,
CC ChEBI:CHEBI:90812; Evidence={ECO:0000269|PubMed:22068350};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48813;
CC Evidence={ECO:0000305|PubMed:22068350};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 17R-
CC hydroxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + A + H2O;
CC Xref=Rhea:RHEA:48816, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:90814; Evidence={ECO:0000269|PubMed:12391014};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48817;
CC Evidence={ECO:0000305|PubMed:12391014};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 =
CC (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O;
CC Xref=Rhea:RHEA:48808, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632,
CC ChEBI:CHEBI:90813; Evidence={ECO:0000269|PubMed:22068350};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48809;
CC Evidence={ECO:0000305|PubMed:22068350};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 =
CC (5S,11R)-dihydroxy-(6E,8Z,12E,14Z)-eicosatetraenoate + A + H2O;
CC Xref=Rhea:RHEA:48804, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632,
CC ChEBI:CHEBI:90810; Evidence={ECO:0000269|PubMed:22068350,
CC ECO:0000269|PubMed:26282205};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48805;
CC Evidence={ECO:0000305|PubMed:22068350, ECO:0000305|PubMed:26282205};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + 2 O2 = 2-
CC glyceryl-prostaglandin G2; Xref=Rhea:RHEA:45288, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:52392, ChEBI:CHEBI:85165;
CC Evidence={ECO:0000269|PubMed:22942274};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45289;
CC Evidence={ECO:0000305|PubMed:22942274};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-glyceryl-prostaglandin G2 + AH2 = 2-glyceryl-prostaglandin
CC H2 + A + H2O; Xref=Rhea:RHEA:45292, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:85165,
CC ChEBI:CHEBI:85166; Evidence={ECO:0000269|PubMed:22942274};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45293;
CC Evidence={ECO:0000305|PubMed:22942274};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15R)-hydroperoxy-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:42284,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82626;
CC Evidence={ECO:0000269|PubMed:9048568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42285;
CC Evidence={ECO:0000305|PubMed:9048568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 11R-hydroperoxy-
CC (5Z,8Z,12E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:42280,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82628;
CC Evidence={ECO:0000269|PubMed:9048568};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42281;
CC Evidence={ECO:0000305|PubMed:9048568};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593,
CC ECO:0000269|PubMed:27710942};
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
CC {ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593,
CC ECO:0000269|PubMed:27710942};
CC -!- ACTIVITY REGULATION: The cyclooxygenase activity is inhibited by
CC nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin,
CC ibuprofen, flurbiprofen, celecoxib, flufenamic, mefenamic and
CC tolfenamic acids as well as by hydroperoxide scavenger erythrocyte
CC glutathione peroxidase GPX1 (PubMed:26859324, PubMed:27226593,
CC PubMed:7592599, PubMed:9048568). Aspirin triggers enzyme acetylation
CC turning off its ability to generate pro-inflammatory prostaglandins,
CC but switches on its capacity to produce anti-inflammatory lipid
CC mediators involved in inflammation resolution (PubMed:11034610,
CC PubMed:12391014). Aspirin enhances lipoxygenase-type activity toward
CC production of epimers with R stereochemistry such as 15R-HETE, 18R-
CC HEPE, 15R-HEPE and 17R-HDHA (PubMed:11034610, PubMed:11192938,
CC PubMed:22068350, PubMed:12391014, PubMed:9048568, PubMed:21206090).
CC Atorvastatin, a cholesterol-lowering drug, triggers enzyme S-
CC nitrosylation increasing production of 13-series resolvins (RvTs)
CC (PubMed:26236990). {ECO:0000269|PubMed:11034610,
CC ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:12391014,
CC ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:22068350,
CC ECO:0000269|PubMed:26236990, ECO:0000269|PubMed:9048568}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16.2 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (in absence of
CC sodium nitroprusside NO donor) {ECO:0000269|PubMed:16373578};
CC KM=12 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:26859324};
CC KM=17.0 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (in presence of
CC sodium nitroprusside NO donor) {ECO:0000269|PubMed:16373578};
CC KM=5.1 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (cyclooxygenase and
CC peroxidase activities) {ECO:0000269|PubMed:7947975};
CC KM=3.1 uM for (7Z,10Z,13Z,16Z,19Z)-docosapentaenoate
CC {ECO:0000269|PubMed:26236990};
CC KM=0.93 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (cyclooxygenase
CC activity) {ECO:0000269|PubMed:9048568};
CC KM=13 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (cyclooxygenase
CC activity in presence of aspirin) {ECO:0000269|PubMed:9048568};
CC KM=41 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (lipoxygenase
CC activity) {ECO:0000269|PubMed:9048568};
CC KM=15 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (lipoxygenase activity
CC in presence of aspirin) {ECO:0000269|PubMed:9048568};
CC KM=12.3 uM for 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphocholine (oxidation to 11-HETE-LPC)
CC {ECO:0000269|PubMed:27642067};
CC KM=30 uM for 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphocholine (oxidation to 15-HETE-LPC)
CC {ECO:0000269|PubMed:27642067};
CC Vmax=81.3 nmol/min/mg enzyme (in absence of sodium nitroprusside NO
CC donor) {ECO:0000269|PubMed:16373578};
CC Vmax=132 nmol/min/mg enzyme (in absence of sodium nitroprusside NO
CC donor) {ECO:0000269|PubMed:16373578};
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC {ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:26859324,
CC ECO:0000269|PubMed:27226593}.
CC -!- INTERACTION:
CC P35354; Q86V38: ATN1; NbExp=3; IntAct=EBI-6662113, EBI-11954292;
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:9545330};
CC Peripheral membrane protein. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9545330}; Peripheral membrane protein. Nucleus
CC inner membrane {ECO:0000269|PubMed:9545330}; Peripheral membrane
CC protein. Nucleus outer membrane {ECO:0000269|PubMed:9545330};
CC Peripheral membrane protein. Note=Detected on the lumenal side of the
CC endoplasmic reticulum and nuclear envelope.
CC {ECO:0000269|PubMed:9545330}.
CC -!- INDUCTION: By cytokines and mitogens. Up-regulated by IL1B
CC (PubMed:26282205, PubMed:9545330). Up-regulated by lipopolysaccharide
CC (LPS) (PubMed:9545330). {ECO:0000269|PubMed:26282205,
CC ECO:0000269|PubMed:9545330}.
CC -!- PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-
CC nitrosylation may take place on different Cys residues in addition to
CC Cys-526. {ECO:0000269|PubMed:16373578}.
CC -!- PTM: Acetylated at Ser-565 by SPHK1. During neuroinflammation,
CC acetylation by SPHK1 promotes neuronal secretion of specialized
CC preresolving mediators (SPMs), especially 15-R-lipoxin A4, which
CC results in an increase of phagocytic microglia.
CC {ECO:0000250|UniProtKB:Q05769}.
CC -!- MISCELLANEOUS: The conversion of arachidonate to prostaglandin H2 is a
CC 2 step reaction: a cyclooxygenase (COX) reaction which converts
CC arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in
CC which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase
CC reaction occurs in a hydrophobic channel in the core of the enzyme. The
CC peroxidase reaction occurs at a heme-containing active site located
CC near the protein surface. The nonsteroidal anti-inflammatory drugs
CC (NSAIDs) binding site corresponds to the cyclooxygenase active site.
CC -!- MISCELLANEOUS: Conversion of arachidonate to prostaglandin H2 is
CC mediated by 2 different isozymes: the constitutive PTGS1 and the
CC inducible PTGS2. PTGS1 is expressed constitutively and generally
CC produces prostanoids acutely in response to hormonal stimuli to fine-
CC tune physiological processes requiring instantaneous, continuous
CC regulation (e.g. hemostasis). PTGS2 is inducible and typically produces
CC prostanoids that mediate responses to physiological stresses such as
CC infection and inflammation.
CC -!- MISCELLANEOUS: PTGS1 and PTGS2 are the targets of nonsteroidal anti-
CC inflammatory drugs (NSAIDs) including aspirin and ibuprofen
CC (PubMed:27710942, PubMed:26859324, PubMed:27226593). Aspirin is able to
CC produce an irreversible inactivation of the enzyme through a serine
CC acetylation (PubMed:26859324). Inhibition of the PGHSs with NSAIDs
CC acutely reduces inflammation, pain, and fever, and long-term use of
CC these drugs reduces fatal thrombotic events, as well as the development
CC of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme
CC responsible for production of inflammatory prostaglandins. New
CC generation PTGSs inhibitors strive to be selective for PTGS2, to avoid
CC side effects such as gastrointestinal complications and ulceration.
CC {ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593,
CC ECO:0000269|PubMed:27710942}.
CC -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PTGS2ID509ch1q31.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ptgs2/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ptgs2/";
CC ---------------------------------------------------------------------------
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DR EMBL; L15326; AAA35803.1; -; mRNA.
DR EMBL; M90100; AAA58433.1; -; mRNA.
DR EMBL; D28235; BAA05698.1; -; Genomic_DNA.
DR EMBL; U04636; AAA57317.1; -; Genomic_DNA.
DR EMBL; AY462100; AAR23927.1; -; mRNA.
DR EMBL; AY229989; AAO38056.1; -; Genomic_DNA.
DR EMBL; AY382629; AAQ75702.1; -; Genomic_DNA.
DR EMBL; AK292167; BAF84856.1; -; mRNA.
DR EMBL; AL033533; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91216.1; -; Genomic_DNA.
DR EMBL; BC013734; AAH13734.1; -; mRNA.
DR CCDS; CCDS1371.1; -.
DR PIR; A46150; A46150.
DR RefSeq; NP_000954.1; NM_000963.3.
DR PDB; 5F19; X-ray; 2.04 A; A/B=19-569.
DR PDB; 5F1A; X-ray; 2.38 A; A/B=19-570.
DR PDB; 5IKQ; X-ray; 2.41 A; A/B=19-569.
DR PDB; 5IKR; X-ray; 2.34 A; A/B=19-569.
DR PDB; 5IKT; X-ray; 2.45 A; A/B=19-569.
DR PDB; 5IKV; X-ray; 2.51 A; A/B=19-569.
DR PDB; 5KIR; X-ray; 2.70 A; A/B=19-569.
DR PDBsum; 5F19; -.
DR PDBsum; 5F1A; -.
DR PDBsum; 5IKQ; -.
DR PDBsum; 5IKR; -.
DR PDBsum; 5IKT; -.
DR PDBsum; 5IKV; -.
DR PDBsum; 5KIR; -.
DR AlphaFoldDB; P35354; -.
DR SMR; P35354; -.
DR BioGRID; 111715; 42.
DR CORUM; P35354; -.
DR DIP; DIP-28131N; -.
DR IntAct; P35354; 6.
DR STRING; 9606.ENSP00000356438; -.
DR BindingDB; P35354; -.
DR ChEMBL; CHEMBL230; -.
DR DrugBank; DB03477; 1-Phenylsulfonamide-3-Trifluoromethyl-5-Parabromophenylpyrazole.
DR DrugBank; DB06736; Aceclofenac.
DR DrugBank; DB13783; Acemetacin.
DR DrugBank; DB00316; Acetaminophen.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB13167; Alclofenac.
DR DrugBank; DB00041; Aldesleukin.
DR DrugBank; DB00233; Aminosalicylic acid.
DR DrugBank; DB01435; Antipyrine.
DR DrugBank; DB01419; Antrafenine.
DR DrugBank; DB01014; Balsalazide.
DR DrugBank; DB13501; Bendazac.
DR DrugBank; DB00963; Bromfenac.
DR DrugBank; DB11752; Bryostatin 1.
DR DrugBank; DB13346; Bufexamac.
DR DrugBank; DB00887; Bumetanide.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB06774; Capsaicin.
DR DrugBank; DB00821; Carprofen.
DR DrugBank; DB00482; Celecoxib.
DR DrugBank; DB00856; Chlorphenesin.
DR DrugBank; DB01401; Choline magnesium trisalicylate.
DR DrugBank; DB05095; Cimicoxib.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB00720; Clodronic acid.
DR DrugBank; DB00250; Dapsone.
DR DrugBank; DB00035; Desmopressin.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB09214; Dexketoprofen.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB00861; Diflunisal.
DR DrugBank; DB00154; Dihomo-gamma-linolenic acid.
DR DrugBank; DB11327; Dipyrithione.
DR DrugBank; DB01395; Drospirenone.
DR DrugBank; DB09215; Droxicam.
DR DrugBank; DB00749; Etodolac.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB01628; Etoricoxib.
DR DrugBank; DB00573; Fenoprofen.
DR DrugBank; DB09217; Firocoxib.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB02266; Flufenamic acid.
DR DrugBank; DB00712; Flurbiprofen.
DR DrugBank; DB01404; Ginseng.
DR DrugBank; DB11323; Glycol salicylate.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB00159; Icosapent.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB01009; Ketoprofen.
DR DrugBank; DB00465; Ketorolac.
DR DrugBank; DB00480; Lenalidomide.
DR DrugBank; DB04725; Licofelone.
DR DrugBank; DB06725; Lornoxicam.
DR DrugBank; DB09212; Loxoprofen.
DR DrugBank; DB01283; Lumiracoxib.
DR DrugBank; DB01397; Magnesium salicylate.
DR DrugBank; DB00939; Meclofenamic acid.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB00784; Mefenamic acid.
DR DrugBank; DB00814; Meloxicam.
DR DrugBank; DB11201; Menthyl salicylate.
DR DrugBank; DB00244; Mesalazine.
DR DrugBank; DB09285; Morniflumate.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB00461; Nabumetone.
DR DrugBank; DB00788; Naproxen.
DR DrugBank; DB06802; Nepafenac.
DR DrugBank; DB04552; Niflumic acid.
DR DrugBank; DB04743; Nimesulide.
DR DrugBank; DB06804; Nonoxynol-9.
DR DrugBank; DB11133; Omega-3 fatty acids.
DR DrugBank; DB13168; Omega-6 fatty acids.
DR DrugBank; DB00991; Oxaprozin.
DR DrugBank; DB08439; Parecoxib.
DR DrugBank; DB11071; Phenyl salicylate.
DR DrugBank; DB00812; Phenylbutazone.
DR DrugBank; DB00554; Piroxicam.
DR DrugBank; DB08910; Pomalidomide.
DR DrugBank; DB05804; Prasterone sulfate.
DR DrugBank; DB09288; Propacetamol.
DR DrugBank; DB03866; Prostaglandin G2.
DR DrugBank; DB02709; Resveratrol.
DR DrugBank; DB00884; Risedronic acid.
DR DrugBank; DB00533; Rofecoxib.
DR DrugBank; DB00936; Salicylic acid.
DR DrugBank; DB01399; Salsalate.
DR DrugBank; DB00360; Sapropterin.
DR DrugBank; DB05875; Sar9, Met (O2)11-Substance P.
DR DrugBank; DB06195; Seliciclib.
DR DrugBank; DB06436; Semaxanib.
DR DrugBank; DB00795; Sulfasalazine.
DR DrugBank; DB00605; Sulindac.
DR DrugBank; DB00870; Suprofen.
DR DrugBank; DB08819; Tafluprost.
DR DrugBank; DB09295; Talniflumate.
DR DrugBank; DB00469; Tenoxicam.
DR DrugBank; DB01041; Thalidomide.
DR DrugBank; DB01600; Tiaprofenic acid.
DR DrugBank; DB09216; Tolfenamic acid.
DR DrugBank; DB00500; Tolmetin.
DR DrugBank; DB00620; Triamcinolone.
DR DrugBank; DB11079; Trolamine salicylate.
DR DrugBank; DB00580; Valdecoxib.
DR DrugCentral; P35354; -.
DR GuidetoPHARMACOLOGY; 1376; -.
DR SwissLipids; SLP:000000830; -.
DR PeroxiBase; 3321; HsPGHS02.
DR GlyConnect; 1649; 9 N-Linked glycans (3 sites).
DR GlyGen; P35354; 6 sites, 11 N-linked glycans (3 sites).
DR iPTMnet; P35354; -.
DR PhosphoSitePlus; P35354; -.
DR BioMuta; PTGS2; -.
DR DMDM; 3915797; -.
DR EPD; P35354; -.
DR jPOST; P35354; -.
DR MassIVE; P35354; -.
DR MaxQB; P35354; -.
DR PaxDb; P35354; -.
DR PeptideAtlas; P35354; -.
DR PRIDE; P35354; -.
DR ProteomicsDB; 55035; -.
DR Antibodypedia; 776; 1028 antibodies from 49 providers.
DR CPTC; P35354; 1 antibody.
DR DNASU; 5743; -.
DR Ensembl; ENST00000367468.10; ENSP00000356438.5; ENSG00000073756.13.
DR Ensembl; ENST00000680451.1; ENSP00000506242.1; ENSG00000073756.13.
DR GeneID; 5743; -.
DR KEGG; hsa:5743; -.
DR MANE-Select; ENST00000367468.10; ENSP00000356438.5; NM_000963.4; NP_000954.1.
DR UCSC; uc001gsb.4; human.
DR CTD; 5743; -.
DR DisGeNET; 5743; -.
DR GeneCards; PTGS2; -.
DR HGNC; HGNC:9605; PTGS2.
DR HPA; ENSG00000073756; Tissue enhanced (bone marrow, seminal vesicle, urinary bladder).
DR MIM; 600262; gene.
DR neXtProt; NX_P35354; -.
DR OpenTargets; ENSG00000073756; -.
DR PharmGKB; PA293; -.
DR VEuPathDB; HostDB:ENSG00000073756; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00390000010743; -.
DR HOGENOM; CLU_022428_0_0_1; -.
DR InParanoid; P35354; -.
DR OMA; NVHYGYK; -.
DR OrthoDB; 180654at2759; -.
DR PhylomeDB; P35354; -.
DR TreeFam; TF329675; -.
DR BioCyc; MetaCyc:HS01115-MON; -.
DR BRENDA; 1.14.99.1; 2681.
DR PathwayCommons; P35354; -.
DR Reactome; R-HSA-197264; Nicotinamide salvaging.
DR Reactome; R-HSA-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-9018677; Biosynthesis of DHA-derived SPMs.
DR Reactome; R-HSA-9018679; Biosynthesis of EPA-derived SPMs.
DR Reactome; R-HSA-9025094; Biosynthesis of DPAn-3 SPMs.
DR Reactome; R-HSA-9027604; Biosynthesis of electrophilic Omega-3 PUFA oxo-derivatives.
DR SABIO-RK; P35354; -.
DR SignaLink; P35354; -.
DR SIGNOR; P35354; -.
DR UniPathway; UPA00662; -.
DR BioGRID-ORCS; 5743; 3 hits in 1072 CRISPR screens.
DR ChiTaRS; PTGS2; human.
DR GeneWiki; Prostaglandin-endoperoxide_synthase_2; -.
DR GeneWiki; PTGS2; -.
DR GenomeRNAi; 5743; -.
DR Pharos; P35354; Tclin.
DR PRO; PR:P35354; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P35354; protein.
DR Bgee; ENSG00000073756; Expressed in seminal vesicle and 173 other tissues.
DR ExpressionAtlas; P35354; baseline and differential.
DR Genevisible; P35354; HS.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
DR GO; GO:0005640; C:nuclear outer membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IBA:GO_Central.
DR GO; GO:0004601; F:peroxidase activity; NAS:UniProtKB.
DR GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0071318; P:cellular response to ATP; IEA:Ensembl.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
DR GO; GO:0071284; P:cellular response to lead ion; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0071471; P:cellular response to non-ionic osmotic stress; IEA:Ensembl.
DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl.
DR GO; GO:0019371; P:cyclooxygenase pathway; IDA:UniProtKB.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl.
DR GO; GO:0042633; P:hair cycle; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0035633; P:maintenance of blood-brain barrier; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0045786; P:negative regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:1902219; P:negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress; IEA:Ensembl.
DR GO; GO:0045986; P:negative regulation of smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0032227; P:negative regulation of synaptic transmission, dopaminergic; IEA:Ensembl.
DR GO; GO:0030728; P:ovulation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISS:BHF-UCL.
DR GO; GO:0031622; P:positive regulation of fever generation; ISS:BHF-UCL.
DR GO; GO:0090271; P:positive regulation of fibroblast growth factor production; ISS:BHF-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0090362; P:positive regulation of platelet-derived growth factor production; ISS:BHF-UCL.
DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; NAS:BHF-UCL.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0031915; P:positive regulation of synaptic plasticity; IEA:Ensembl.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0071636; P:positive regulation of transforming growth factor beta production; ISS:BHF-UCL.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:BHF-UCL.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0032310; P:prostaglandin secretion; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; NAS:UniProtKB.
DR GO; GO:0150077; P:regulation of neuroinflammatory response; ISS:UniProtKB.
DR GO; GO:1990776; P:response to angiotensin; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0009750; P:response to fructose; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0010226; P:response to lithium ion; IEA:Ensembl.
DR GO; GO:0010042; P:response to manganese ion; IEA:Ensembl.
DR GO; GO:0009624; P:response to nematode; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR029576; COX-2.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR PANTHER; PTHR11903:SF8; PTHR11903:SF8; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00008; EGF; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Dioxygenase; Disulfide bond;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Glycoprotein; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Nucleus; Oxidoreductase; Peroxidase;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW S-nitrosylation; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..604
FT /note="Prostaglandin G/H synthase 2"
FT /id="PRO_0000023875"
FT DOMAIN 18..55
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT ACT_SITE 193
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT ACT_SITE 371
FT /note="For cyclooxygenase activity"
FT /evidence="ECO:0000250|UniProtKB:Q05769"
FT BINDING 106
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q05769"
FT BINDING 341
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q05769"
FT BINDING 374
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT SITE 516
FT /note="Aspirin-acetylated serine"
FT /evidence="ECO:0000269|PubMed:26859324"
FT MOD_RES 526
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000305|PubMed:16373578"
FT MOD_RES 565
FT /note="O-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q05769"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0007744|PDB:5F19,
FT ECO:0007744|PDB:5F1A, ECO:0007744|PDB:5IKQ,
FT ECO:0007744|PDB:5IKT"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27710942,
FT ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A,
FT ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR,
FT ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV,
FT ECO:0007744|PDB:5KIR"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27710942,
FT ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A,
FT ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR,
FT ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV,
FT ECO:0007744|PDB:5KIR"
FT CARBOHYD 580
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17113084"
FT DISULFID 21..32
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27710942,
FT ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A,
FT ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR,
FT ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV,
FT ECO:0007744|PDB:5KIR"
FT DISULFID 22..145
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27710942,
FT ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A,
FT ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR,
FT ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV,
FT ECO:0007744|PDB:5KIR"
FT DISULFID 26..42
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27710942,
FT ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A,
FT ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR,
FT ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV,
FT ECO:0007744|PDB:5KIR"
FT DISULFID 44..54
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27710942,
FT ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A,
FT ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR,
FT ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV,
FT ECO:0007744|PDB:5KIR"
FT DISULFID 555..561
FT /evidence="ECO:0000269|PubMed:26859324,
FT ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27710942,
FT ECO:0007744|PDB:5F19, ECO:0007744|PDB:5F1A,
FT ECO:0007744|PDB:5IKQ, ECO:0007744|PDB:5IKR,
FT ECO:0007744|PDB:5IKT, ECO:0007744|PDB:5IKV,
FT ECO:0007744|PDB:5KIR"
FT VARIANT 228
FT /note="R -> H (in dbSNP:rs3218622)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_016262"
FT VARIANT 428
FT /note="P -> A (in dbSNP:rs4648279)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_016263"
FT VARIANT 488
FT /note="E -> G (in dbSNP:rs5272)"
FT /id="VAR_011980"
FT VARIANT 511
FT /note="V -> A (in dbSNP:rs5273)"
FT /evidence="ECO:0000269|PubMed:15308583, ECO:0000269|Ref.6"
FT /id="VAR_011981"
FT VARIANT 587
FT /note="G -> R (in dbSNP:rs3218625)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_016264"
FT MUTAGEN 189
FT /note="Q->N: Increases two-electron hydroperoxide
FT reduction. Has no effect on cyclooxygenase activity."
FT /evidence="ECO:0000269|PubMed:9261177"
FT MUTAGEN 189
FT /note="Q->R: Impairs two-electron hydroperoxide reduction
FT and cyclooxygenase activity."
FT /evidence="ECO:0000269|PubMed:9261177"
FT MUTAGEN 189
FT /note="Q->V: Impairs two-electron hydroperoxide reduction."
FT /evidence="ECO:0000269|PubMed:9261177"
FT MUTAGEN 193
FT /note="H->A: Reduces two-electron hydroperoxide reduction
FT and cyclooxygenase activity. Catalyzes predominantly one-
FT electron hydroperoxide reduction."
FT /evidence="ECO:0000269|PubMed:9261177"
FT MUTAGEN 371
FT /note="Y->A: Decreased protein stability. Increased
FT decrease of protein stability; when associated with A-516."
FT /evidence="ECO:0000269|PubMed:27226593"
FT MUTAGEN 516
FT /note="S->A: No effect on protein stability. Increased
FT decrease of protein stability; when associated with A-371."
FT /evidence="ECO:0000269|PubMed:27226593"
FT MUTAGEN 516
FT /note="S->T: Decreased enzyme activity with arachidonic
FT acid. Loss of cyclooxygenase activity; when associated with
FT V-519."
FT /evidence="ECO:0000269|PubMed:26859324"
FT MUTAGEN 519
FT /note="G->V: Loss of cyclooxygenase activity. Loss of
FT cyclooxygenase activity; when associated with T-516."
FT /evidence="ECO:0000269|PubMed:26859324"
FT MUTAGEN 526
FT /note="C->S: Prevents activation by nitric oxid (NO)."
FT /evidence="ECO:0000269|PubMed:16373578"
FT MUTAGEN 555
FT /note="C->S: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:16373578"
FT MUTAGEN 561
FT /note="C->S: Does not affect activation by nitric oxid
FT (NO)."
FT /evidence="ECO:0000269|PubMed:16373578"
FT CONFLICT 165
FT /note="E -> G (in Ref. 2; AAA58433)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="I -> T (in Ref. 1; AAA35803)"
FT /evidence="ECO:0000305"
FT TURN 20..23
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:5F19"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:5F19"
FT TURN 51..54
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 59..66
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 71..78
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 92..107
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 125..129
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 135..138
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 182..192
FT /evidence="ECO:0007829|PDB:5F19"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:5F19"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 252..255
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:5F19"
FT TURN 276..279
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 282..305
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 311..332
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 334..339
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 349..352
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 365..370
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 379..383
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 398..414
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 420..424
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 431..443
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 449..455
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 464..468
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 472..481
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 484..486
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 489..495
FT /evidence="ECO:0007829|PDB:5F19"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 506..521
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:5F19"
FT TURN 528..530
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 533..536
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 539..546
FT /evidence="ECO:0007829|PDB:5F19"
FT HELIX 550..557
FT /evidence="ECO:0007829|PDB:5F19"
SQ SEQUENCE 604 AA; 68996 MW; 72FBD699F6128519 CRC64;
MLARALLLCA VLALSHTANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY GENCSTPEFL
TRIKLFLKPT PNTVHYILTH FKGFWNVVNN IPFLRNAIMS YVLTSRSHLI DSPPTYNADY
GYKSWEAFSN LSYYTRALPP VPDDCPTPLG VKGKKQLPDS NEIVEKLLLR RKFIPDPQGS
NMMFAFFAQH FTHQFFKTDH KRGPAFTNGL GHGVDLNHIY GETLARQRKL RLFKDGKMKY
QIIDGEMYPP TVKDTQAEMI YPPQVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD
VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNKQFQYQ
NRIAAEFNTL YHWHPLLPDT FQIHDQKYNY QQFIYNNSIL LEHGITQFVE SFTRQIAGRV
AGGRNVPPAV QKVSQASIDQ SRQMKYQSFN EYRKRFMLKP YESFEELTGE KEMSAELEAL
YGDIDAVELY PALLVEKPRP DAIFGETMVE VGAPFSLKGL MGNVICSPAY WKPSTFGGEV
GFQIINTASI QSLICNNVKG CPFTSFSVPD PELIKTVTIN ASSSRSGLDD INPTVLLKER
STEL
