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 11-NOV-2015, entry version 171. DE RecName: Full=Prostaglandin G/H synthase 2; DE EC=1.14.99.1; DE AltName: Full=Cyclooxygenase-2; DE Short=COX-2; 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; Synonyms=COX2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Endothelial cell; RX PubMed=8473346; RA Jones D.A., Carlton D.P., McIntyre T.M., Zimmerman G.A., RA Prescott S.M.; RT "Molecular cloning of human prostaglandin endoperoxide synthase type RT II and 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; 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 RT sequenced by 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; RP ALA-511 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP CHARACTERIZATION. RX PubMed=7947975; DOI=10.1016/0167-4838(94)90148-1; RA Barnett J., Chow J., Ives D., Chiou M., Mackenzie R., Osen E., RA Nguyen B., 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 RT system."; RL Biochim. Biophys. Acta 1209:130-139(1994). RN [13] 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 [14] 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 [15] 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) RT polymorphisms and colon cancer risk."; RL Carcinogenesis 25:2467-2472(2004). RN [16] 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 [17] RP REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN RP COLORECTAL 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). CC -!- FUNCTION: Converts arachidonate to prostaglandin H2 (PGH2), a CC committed step in prostanoid synthesis. Constitutively expressed CC in some tissues in physiological conditions, such as the CC endothelium, kidney and brain, and in pathological conditions, CC such as in cancer. PTGS2 is responsible for production of CC inflammatory prostaglandins. Up-regulation of PTGS2 is also CC associated with increased cell adhesion, phenotypic changes, CC resistance to apoptosis and tumor angiogenesis. In cancer cells, CC PTGS2 is a key step in the production of prostaglandin E2 (PGE2), CC which plays important roles in modulating motility, proliferation CC and resistance to apoptosis. {ECO:0000269|PubMed:16373578}. CC -!- CATALYTIC ACTIVITY: Arachidonate + AH(2) + 2 O(2) = prostaglandin CC H(2) + A + H(2)O. {ECO:0000269|PubMed:16373578}. CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250}; CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per CC subunit. {ECO:0000250}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=16.2 uM for arachidonate (in absence of sodium nitroprusside CC NO donor) {ECO:0000269|PubMed:16373578}; CC KM=17.0 uM for arachidonate (in presence of sodium nitroprusside CC NO donor) {ECO:0000269|PubMed:16373578}; CC Vmax=81.3 nmol/min/mg enzyme (in absence of sodium nitroprusside CC NO donor) {ECO:0000269|PubMed:16373578}; CC Vmax=132 nmol/min/mg enzyme (in absence of sodium nitroprusside CC NO donor) {ECO:0000269|PubMed:16373578}; CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis. CC -!- SUBUNIT: Homodimer. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane CC protein. Endoplasmic reticulum membrane; Peripheral membrane CC protein. CC -!- INDUCTION: By cytokines and mitogens. CC -!- PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S- CC nitrosylation may take place on different Cys residues in addition CC to Cys-526. {ECO:0000269|PubMed:16373578}. CC -!- MISCELLANEOUS: The conversion of arachidonate to prostaglandin H2 CC is a 2 step reaction: a cyclooxygenase (COX) reaction which CC converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase CC reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The CC cyclooxygenase reaction occurs in a hydrophobic channel in the CC core of the enzyme. The peroxidase reaction occurs at a heme- CC containing active site located near the protein surface. The CC nonsteroidal anti-inflammatory drugs (NSAIDs) binding site CC 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. PGHS1 is expressed constitutively and generally CC produces prostanoids acutely in response to hormonal stimuli to CC fine-tune physiological processes requiring instantaneous, CC continuous regulation (e.g. hemostasis). PGHS2 is inducible and CC typically produces prostanoids that mediate responses to CC physiological stresses such as infection and inflammation. CC -!- MISCELLANEOUS: PTGS1 and PTGS2 are the targets of nonsteroidal CC anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. CC Aspirin is able to produce an irreversible inactivation of the CC enzyme through a serine acetylation. Inhibition of the PGHSs with CC NSAIDs acutely reduces inflammation, pain, and fever, and long- CC term use of these drugs reduces fatal thrombotic events, as well CC as the development of colon cancer and Alzheimer's disease. PTGS2 CC is the principal isozyme responsible for production of CC inflammatory prostaglandins. New generation PTGSs inhibitors CC strive to be selective for PTGS2, to avoid side effects such as CC gastrointestinal complications and ulceration. CC -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 EGF-like domain. {ECO:0000255|PROSITE- CC ProRule:PRU00076}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and 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 --------------------------------------------------------------------------- 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; CAB41240.1; -; 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 UniGene; Hs.196384; -. DR PDB; 1V0X; Model; -; A=1-604. DR PDBsum; 1V0X; -. DR ProteinModelPortal; P35354; -. DR SMR; P35354; 18-568. DR BioGrid; 111715; 28. DR DIP; DIP-28131N; -. DR IntAct; P35354; 2. DR MINT; MINT-203337; -. DR STRING; 9606.ENSP00000356438; -. DR BindingDB; P35354; -. DR ChEMBL; CHEMBL2094253; -. DR DrugBank; DB00316; Acetaminophen. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB00041; Aldesleukin. DR DrugBank; DB00233; Aminosalicylic Acid. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB01419; Antrafenine. DR DrugBank; DB01014; Balsalazide. DR DrugBank; DB00963; Bromfenac. DR DrugBank; DB00887; Bumetanide. DR DrugBank; DB00821; Carprofen. DR DrugBank; DB00482; Celecoxib. DR DrugBank; DB00856; Chlorphenesin. DR DrugBank; DB00515; Cisplatin. DR DrugBank; DB00720; Clodronate. DR DrugBank; DB00250; Dapsone. DR DrugBank; DB00035; Desmopressin. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB00861; Diflunisal. DR DrugBank; DB00154; Dihomo-gamma-linolenic acid. DR DrugBank; DB01395; Drospirenone. DR DrugBank; DB00005; Etanercept. DR DrugBank; DB00749; Etodolac. DR DrugBank; DB00773; Etoposide. DR DrugBank; DB01628; Etoricoxib. DR DrugBank; DB00573; Fenoprofen. DR DrugBank; DB00712; Flurbiprofen. DR DrugBank; DB01404; Ginseng. 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; DB06725; Lornoxicam. DR DrugBank; DB01283; Lumiracoxib. DR DrugBank; DB01397; Magnesium salicylate. DR DrugBank; DB00939; Meclofenamic acid. DR DrugBank; DB00784; Mefenamic acid. DR DrugBank; DB00814; Meloxicam. DR DrugBank; DB00244; Mesalazine. DR DrugBank; DB00461; Nabumetone. DR DrugBank; DB00788; Naproxen. DR DrugBank; DB06802; Nepafenac. DR DrugBank; DB04552; Niflumic Acid. DR DrugBank; DB06804; Nonoxynol-9. DR DrugBank; DB00991; Oxaprozin. DR DrugBank; DB00812; Phenylbutazone. DR DrugBank; DB00554; Piroxicam. DR DrugBank; DB08910; Pomalidomide. DR DrugBank; DB00884; Risedronate. DR DrugBank; DB01398; Salicylate-sodium. DR DrugBank; DB00936; Salicylic acid. DR DrugBank; DB01399; Salsalate. DR DrugBank; DB00795; Sulfasalazine. DR DrugBank; DB00605; Sulindac. DR DrugBank; DB00870; Suprofen. DR DrugBank; DB08819; Tafluprost. DR DrugBank; DB00469; Tenoxicam. DR DrugBank; DB00360; Tetrahydrobiopterin. DR DrugBank; DB01041; Thalidomide. DR DrugBank; DB01600; Tiaprofenic acid. DR DrugBank; DB00500; Tolmetin. DR DrugBank; DB00620; Triamcinolone. DR DrugBank; DB01401; Trisalicylate-choline. DR GuidetoPHARMACOLOGY; 1376; -. DR PeroxiBase; 3321; HsPGHS02. DR PhosphoSite; P35354; -. DR BioMuta; PTGS2; -. DR DMDM; 3915797; -. DR MaxQB; P35354; -. DR PaxDb; P35354; -. DR PRIDE; P35354; -. DR DNASU; 5743; -. DR Ensembl; ENST00000367468; ENSP00000356438; ENSG00000073756. DR GeneID; 5743; -. DR KEGG; hsa:5743; -. DR UCSC; uc001gsb.3; human. DR CTD; 5743; -. DR GeneCards; PTGS2; -. DR HGNC; HGNC:9605; PTGS2. DR HPA; CAB000113; -. DR HPA; HPA001335; -. DR MIM; 600262; gene. DR neXtProt; NX_P35354; -. DR PharmGKB; PA293; -. DR eggNOG; KOG2408; Eukaryota. DR eggNOG; ENOG410XPZ3; LUCA. DR GeneTree; ENSGT00390000010743; -. DR HOGENOM; HOG000013149; -. DR HOVERGEN; HBG000366; -. DR InParanoid; P35354; -. DR KO; K11987; -. DR OMA; CNNVKGC; -. DR OrthoDB; EOG7RFTHC; -. DR PhylomeDB; P35354; -. DR TreeFam; TF329675; -. DR BioCyc; MetaCyc:HS01115-MONOMER; -. DR BRENDA; 1.14.99.1; 2681. 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 SABIO-RK; P35354; -. DR UniPathway; UPA00662; -. DR GeneWiki; Prostaglandin-endoperoxide_synthase_2; -. DR GeneWiki; PTGS2; -. DR GenomeRNAi; 5743; -. DR NextBio; 22358; -. DR PRO; PR:P35354; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; P35354; -. DR CleanEx; HS_PTGS2; -. 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:0043005; C:neuron projection; IDA:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0043234; C:protein complex; IEA:Ensembl. DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; TAS:Reactome. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0020037; F:heme binding; ISS:UniProtKB. DR GO; GO:0008289; F:lipid binding; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004601; F:peroxidase activity; NAS:UniProtKB. DR GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome. 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:0071456; P:cellular response to hypoxia; IEP:UniProtKB. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl. DR GO; GO:0019371; P:cyclooxygenase pathway; IDA:BHF-UCL. 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:0019372; P:lipoxygenase pathway; TAS:Reactome. DR GO; GO:0035633; P:maintenance of blood-brain barrier; IEA:Ensembl. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0006928; P:movement of cell or subcellular component; TAS:ProtInc. DR GO; GO:0019674; P:NAD metabolic process; TAS:Reactome. 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 proliferation; 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:0006769; P:nicotinamide metabolic process; TAS:Reactome. 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:0042346; P:positive regulation of NF-kappaB import into nucleus; IEA:Ensembl. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:BHF-UCL. 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: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; ISS:UniProtKB. DR GO; GO:0006693; P:prostaglandin metabolic process; TAS:ProtInc. 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:0042493; P:response to drug; 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: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:0019233; P:sensory perception of pain; IEA:Ensembl. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006766; P:vitamin metabolic process; TAS:Reactome. DR GO; GO:0006767; P:water-soluble vitamin metabolic process; TAS:Reactome. DR Gene3D; 1.10.640.10; -; 1. DR InterPro; IPR029576; COX-2. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR010255; Haem_peroxidase. DR InterPro; IPR019791; Haem_peroxidase_animal. DR PANTHER; PTHR11903:SF8; PTHR11903:SF8; 1. DR Pfam; PF03098; An_peroxidase; 1. DR Pfam; PF00008; EGF; 1. DR PRINTS; PR00457; ANPEROXIDASE. DR SMART; SM00181; EGF; 1. 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; Complete proteome; Dioxygenase; Disulfide bond; KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism; KW Glycoprotein; Heme; Iron; Lipid biosynthesis; Lipid metabolism; KW Membrane; Metal-binding; Microsome; Oxidoreductase; Peroxidase; KW Polymorphism; Prostaglandin biosynthesis; Prostaglandin metabolism; KW Reference proteome; S-nitrosylation; Signal. FT SIGNAL 1 17 {ECO:0000255}. FT CHAIN 18 604 Prostaglandin G/H synthase 2. FT /FTId=PRO_0000023875. FT DOMAIN 18 55 EGF-like. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT ACT_SITE 193 193 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00298}. FT ACT_SITE 371 371 For cyclooxygenase activity. FT {ECO:0000250}. FT METAL 374 374 Iron (heme axial ligand). FT {ECO:0000255|PROSITE-ProRule:PRU00298}. FT BINDING 106 106 Substrate. {ECO:0000250}. FT BINDING 341 341 Substrate. {ECO:0000250}. FT BINDING 371 371 Substrate. {ECO:0000250}. FT SITE 516 516 Aspirin-acetylated serine. {ECO:0000250}. FT MOD_RES 526 526 S-nitrosocysteine. FT {ECO:0000305|PubMed:16373578}. FT CARBOHYD 53 53 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 130 130 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 396 396 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 580 580 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:17113084}. FT DISULFID 21 32 {ECO:0000250}. FT DISULFID 22 145 {ECO:0000250}. FT DISULFID 26 42 {ECO:0000250}. FT DISULFID 44 54 {ECO:0000250}. FT DISULFID 555 561 {ECO:0000250}. FT VARIANT 228 228 R -> H (in dbSNP:rs3218622). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_016262. FT VARIANT 428 428 P -> A (in dbSNP:rs4648279). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_016263. FT VARIANT 488 488 E -> G (in dbSNP:rs5272). FT /FTId=VAR_011980. FT VARIANT 511 511 V -> A (in dbSNP:rs5273). FT {ECO:0000269|PubMed:15308583, FT ECO:0000269|Ref.6}. FT /FTId=VAR_011981. FT VARIANT 587 587 G -> R (in dbSNP:rs3218625). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_016264. FT MUTAGEN 526 526 C->S: Prevents activation by nitric oxid FT (NO). {ECO:0000269|PubMed:16373578}. FT MUTAGEN 555 555 C->S: Abolishes enzyme activity. FT {ECO:0000269|PubMed:16373578}. FT MUTAGEN 561 561 C->S: Does not affect activation by FT nitric oxid (NO). FT {ECO:0000269|PubMed:16373578}. FT CONFLICT 165 165 E -> G (in Ref. 2; AAA58433). FT {ECO:0000305}. FT CONFLICT 438 438 I -> T (in Ref. 1; AAA35803). FT {ECO:0000305}. 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 //