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 27-MAR-2024, entry version 230. 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 ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with CC a particular role in the inflammatory response (PubMed:7947975, CC PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, CC PubMed:26859324, PubMed:27226593, PubMed:11939906, PubMed:19540099). CC The cyclooxygenase activity oxygenates AA to the hydroperoxy CC endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity CC reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the CC precursor of all 2-series prostaglandins and thromboxanes CC (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, CC PubMed:22942274, PubMed:26859324, PubMed:27226593). This complex CC transformation is initiated by abstraction of hydrogen at carbon 13 CC (with S-stereochemistry), followed by insertion of molecular O2 to form CC 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). Can also use linoleate (LA, (9Z,12Z)- CC octadecadienoate, C18:2(n-6)) as substrate and produce CC hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, CC being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)- CC HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By CC similarity). 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:P79208, ECO:0000250|UniProtKB:Q05769, CC ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938, CC ECO:0000269|PubMed:11939906, ECO:0000269|PubMed:12391014, CC ECO:0000269|PubMed:16373578, ECO:0000269|PubMed:21206090, CC ECO:0000269|PubMed:22068350, ECO:0000269|PubMed:22942274, CC ECO:0000269|PubMed:26236990, ECO:0000269|PubMed:26282205, CC ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593, CC ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7592599, CC ECO:0000269|PubMed:7947975, ECO:0000269|PubMed:9048568, CC ECO:0000269|PubMed:9261177, 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 (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + 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 -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (9R)-hydroxy-(10E,12Z)- CC octadecadienoate + A + H2O; Xref=Rhea:RHEA:75447, ChEBI:CHEBI:13193, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:77895; CC Evidence={ECO:0000250|UniProtKB:P79208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75448; CC Evidence={ECO:0000250|UniProtKB:P79208}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (9S)-hydroxy-(10E,12Z)- CC octadecadienoate + A + H2O; Xref=Rhea:RHEA:75459, ChEBI:CHEBI:13193, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:77852; CC Evidence={ECO:0000250|UniProtKB:P79208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75460; CC Evidence={ECO:0000250|UniProtKB:P79208}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (13S)-hydroxy-(9Z,11E)- CC octadecadienoate + A + H2O; Xref=Rhea:RHEA:75451, ChEBI:CHEBI:13193, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:90850; CC Evidence={ECO:0000250|UniProtKB:P79208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75452; CC Evidence={ECO:0000250|UniProtKB:P79208}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (13R)-hydroxy-(9Z,11E)- CC octadecadienoate + A + H2O; Xref=Rhea:RHEA:75455, ChEBI:CHEBI:13193, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:136655; CC Evidence={ECO:0000250|UniProtKB:P79208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75456; CC Evidence={ECO:0000250|UniProtKB:P79208}; 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 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (in presence of sodium CC 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 CC 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine CC (oxidation to 11-HETE-LPC) {ECO:0000269|PubMed:27642067}; CC KM=30 uM for CC 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine CC (oxidation to 15-HETE-LPC) {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="https://atlasgeneticsoncology.org/gene/509/PTGS2"; 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 43. DR CORUM; P35354; -. DR DIP; DIP-28131N; -. DR IntAct; P35354; 8. DR MINT; P35354; -. 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; DB14060; NS-398. 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; DB13514; Pranoprofen. 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 GlyCosmos; P35354; 4 sites, 11 glycans. DR GlyGen; P35354; 6 sites, 11 N-linked glycans (3 sites). DR iPTMnet; P35354; -. DR PhosphoSitePlus; P35354; -. DR SwissPalm; P35354; -. DR BioMuta; PTGS2; -. DR DMDM; 3915797; -. DR CPTAC; CPTAC-5960; -. DR EPD; P35354; -. DR jPOST; P35354; -. DR MassIVE; P35354; -. DR MaxQB; P35354; -. DR PaxDb; 9606-ENSP00000356438; -. DR PeptideAtlas; P35354; -. DR ProteomicsDB; 55035; -. DR Pumba; P35354; -. DR Antibodypedia; 776; 1258 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 AGR; HGNC:9605; -. 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; 1086441at2759; -. DR PhylomeDB; P35354; -. DR TreeFam; TF329675; -. DR BioCyc; MetaCyc:HS01115-MONOMER; -. 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 1160 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 175 other cell types or tissues. DR ExpressionAtlas; P35354; baseline and differential. 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: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: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: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: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: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: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: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 CDD; cd00054; EGF_CA; 1. DR CDD; cd09816; prostaglandin_endoperoxide_synthase; 1. DR Gene3D; 1.10.640.10; Haem peroxidase domain superfamily, animal type; 1. DR Gene3D; 2.10.25.10; Laminin; 1. 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; PROSTAGLANDIN G/H SYNTHASE; 1. DR PANTHER; PTHR11903:SF8; PROSTAGLANDIN G_H SYNTHASE 2; 1. DR Pfam; PF03098; An_peroxidase; 1. DR PRINTS; PR00457; ANPEROXIDASE. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF48113; Heme-dependent peroxidases; 1. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS50292; PEROXIDASE_3; 1. DR Genevisible; P35354; HS. 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 FT one-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 //