ID Q8JH43_DANRE Unreviewed; 601 AA. AC Q8JH43; DT 01-OCT-2002, integrated into UniProtKB/TrEMBL. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 150. DE RecName: Full=Prostaglandin G/H synthase 2 {ECO:0000256|ARBA:ARBA00020406}; DE EC=1.14.99.1 {ECO:0000256|ARBA:ARBA00012440}; DE AltName: Full=Cyclooxygenase-2 {ECO:0000256|ARBA:ARBA00031216}; DE AltName: Full=PHS II {ECO:0000256|ARBA:ARBA00030839}; DE AltName: Full=Prostaglandin H2 synthase 2 {ECO:0000256|ARBA:ARBA00031793}; DE AltName: Full=Prostaglandin-endoperoxide synthase 2 {ECO:0000256|ARBA:ARBA00033144}; GN Name=ptgs2a {ECO:0000313|EMBL:AAH56736.1, GN ECO:0000313|RefSeq:NP_705943.1, ECO:0000313|ZFIN:ZDB-GENE-020530-2}; GN Synonyms=fj02a10 {ECO:0000313|RefSeq:NP_705943.1}, ptgs2 GN {ECO:0000313|EMBL:AAK33031.1, ECO:0000313|RefSeq:NP_705943.1}, unp1239 GN {ECO:0000313|RefSeq:NP_705943.1}, zCOX-2 GN {ECO:0000313|RefSeq:NP_705943.1}; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955 {ECO:0000313|EMBL:AAK33031.1}; RN [1] {ECO:0000313|EMBL:AAK33031.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=12011329; DOI=10.1073/pnas.112217799; RA Grosser T., Yusuff S., Cheskis E., Pack M.A., FitzGerald G.A.; RT "Developmental expression of functional cyclooxygenases in zebrafish."; RL Proc. Natl. Acad. Sci. U.S.A. 99:8418-8423(2002). RN [2] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=12093922; RA Prescott S.M., Yost H.J.; RT "The COXes of Danio: from mechanistic model to experimental therapeutics."; RL Proc. Natl. Acad. Sci. U.S.A. 99:9084-9086(2002). RN [3] {ECO:0000313|EMBL:AAH56736.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney {ECO:0000313|EMBL:AAH56736.1}; RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=15576635; DOI=10.1161/01.ATV.0000152355.97808.10; RA Pini B., Grosser T., Lawson J.A., Price T.S., Pack M.A., FitzGerald G.A.; RT "Prostaglandin E synthases in zebrafish."; RL Arterioscler. Thromb. Vasc. Biol. 25:315-320(2005). RN [5] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=15936346; RA Cha Y.I., Kim S.H., Solnica-Krezel L., Dubois R.N.; RT "Cyclooxygenase-1 signaling is required for vascular tube formation during RT development."; RL Dev. Biol. 282:274-283(2005). RN [6] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=16109975; RA Woods I.G., Wilson C., Friedlander B., Chang P., Reyes D.K., Nix R., RA Kelly P.D., Chu F., Postlethwait J.H., Talbot W.S.; RT "The zebrafish gene map defines ancestral vertebrate chromosomes."; RL Genome Res. 15:1307-1314(2005). RN [7] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=16391234; DOI=10.1101/gad.1374506; RA Cha Y.I., Kim S.H., Sepich D., Buchanan F.G., Solnica-Krezel L., RA DuBois R.N.; RT "Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein- RT coupled EP4 receptor during vertebrate gastrulation."; RL Genes Dev. 20:77-86(2006). RN [8] {ECO:0000313|Proteomes:UP000000437} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=23594743; DOI=10.1038/nature12111; RG Genome Reference Consortium Zebrafish; RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I., RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J., RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y., RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B., RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S., RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D., RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B., RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M., RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M., RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J., RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D., RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K., RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R., RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M., RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D., RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M., RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M., RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D., RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J., RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I., RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M., RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M., RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B., RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P., RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R., RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I., RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H., RA Rogers J., Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the human RT genome."; RL Nature 496:498-503(2013). RN [9] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=30213642; RA Li J.J., Zhang Y., Han L.W., Tian Q.P., He Q.X., Wang X.M., Sun C., Han J., RA Liu K.C.; RT "Tenacissoside H exerts an anti-inflammatory effect by regulating the nf- RT kappab and p38 pathways in zebrafish."; RL Fish Shellfish Immunol. 83:205-212(2018). RN [10] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=30237797; RA Nayak S., Khozin-Goldberg I., Cohen G., Zilberg D.; RT "Dietary Supplementation With omega6 LC-PUFA-Rich Algae Modulates Zebrafish RT Immune Function and Improves Resistance to Streptococcal Infection."; RL Front. Immunol. 9:1960-1960(2018). RN [11] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=30685088; RA Li W., Jin D., Zhong T.P.; RT "Photoreceptor cell development requires prostaglandin signaling in the RT zebrafish retina."; RL Biochem. Biophys. Res. Commun. 510:230-235(2019). RN [12] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=30389644; RA Jiang M., Gong Q.Y., Lai S.S., Cheng Z.X., Chen Z.G., Zheng J., Peng B.; RT "Phenylalanine enhances innate immune response to clear ceftazidime- RT resistant Vibrio alginolyticus in Danio rerio."; RL Fish Shellfish Immunol. 84:912-919(2019). RN [13] {ECO:0000313|RefSeq:NP_705943.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=30455348; RA Hwang J.S., Kim K.H., Park J., Kim S.M., Cho H., Lee Y., Han I.O.; RT "Glucosamine improves survival in a mouse model of sepsis and attenuates RT sepsis-induced lung injury and inflammation."; RL J. Biol. Chem. 294:608-622(2019). RN [14] {ECO:0000313|RefSeq:NP_705943.1} RP IDENTIFICATION. RG RefSeq; RL Submitted (NOV-2023) to UniProtKB. 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:0000256|ARBA:ARBA00036409}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75456; CC Evidence={ECO:0000256|ARBA:ARBA00036409}; 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:0000256|ARBA:ARBA00036358}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75452; CC Evidence={ECO:0000256|ARBA:ARBA00036358}; 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:0000256|ARBA:ARBA00036313}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75448; CC Evidence={ECO:0000256|ARBA:ARBA00036313}; 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:0000256|ARBA:ARBA00035976}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75460; CC Evidence={ECO:0000256|ARBA:ARBA00035976}; CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; CC Evidence={ECO:0000256|ARBA:ARBA00001970}; CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis. CC {ECO:0000256|ARBA:ARBA00004702}. CC -!- SUBUNIT: Homodimer. {ECO:0000256|ARBA:ARBA00011738}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000256|ARBA:ARBA00004406}; Peripheral membrane protein CC {ECO:0000256|ARBA:ARBA00004406}. Membrane CC {ECO:0000256|ARBA:ARBA00004170}; Peripheral membrane protein CC {ECO:0000256|ARBA:ARBA00004170}. Microsome membrane CC {ECO:0000256|ARBA:ARBA00004174}; Peripheral membrane protein CC {ECO:0000256|ARBA:ARBA00004174}. CC -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family. CC {ECO:0000256|ARBA:ARBA00008928}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00076}. 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; BC056736; AAH56736.1; -; mRNA. DR EMBL; AY028585; AAK33031.1; -; mRNA. DR RefSeq; NP_705943.1; NM_153657.1. DR PeroxiBase; 3364; DrPGHS02. DR GeneID; 246227; -. DR KEGG; dre:246227; -. DR AGR; ZFIN:ZDB-GENE-020530-2; -. DR CTD; 246227; -. DR ZFIN; ZDB-GENE-020530-2; ptgs2a. DR OrthoDB; 1086441at2759; -. DR UniPathway; UPA00662; -. DR Proteomes; UP000000437; Chromosome 2. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0020037; F:heme binding; IEA:InterPro. 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; IDA:ZFIN. DR GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; IBA:GO_Central. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:ZFIN. DR GO; GO:0019371; P:cyclooxygenase pathway; IBA:GO_Central. DR GO; GO:1990402; P:embryonic liver development; IMP:ZFIN. DR GO; GO:0031017; P:exocrine pancreas development; IMP:ZFIN. DR GO; GO:0048793; P:pronephros development; IMP:ZFIN. DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro. DR GO; GO:0048545; P:response to steroid hormone; IEP:ZFIN. 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. PE 2: Evidence at transcript level; KW Dioxygenase {ECO:0000256|ARBA:ARBA00022964}; KW EGF-like domain {ECO:0000256|PROSITE-ProRule:PRU00076}; KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824}; KW Fatty acid biosynthesis {ECO:0000256|ARBA:ARBA00023160}; KW Fatty acid metabolism {ECO:0000256|ARBA:ARBA00022832}; KW Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|PIRSR:PIRSR619791-2}; KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRSR:PIRSR619791-2}; KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516}; KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098}; KW Metal-binding {ECO:0000256|PIRSR:PIRSR619791-2}; KW Microsome {ECO:0000256|ARBA:ARBA00022848}; KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002}; KW Peroxidase {ECO:0000256|ARBA:ARBA00022559}; KW Prostaglandin biosynthesis {ECO:0000256|ARBA:ARBA00022585}; KW Prostaglandin metabolism {ECO:0000256|ARBA:ARBA00022501}; KW Reference proteome {ECO:0000313|Proteomes:UP000000437}; KW Signal {ECO:0000256|SAM:SignalP, ECO:0000313|RefSeq:NP_705943.1}. FT SIGNAL 1..20 FT /evidence="ECO:0000256|SAM:SignalP" FT CHAIN 21..601 FT /note="Prostaglandin G/H synthase 2" FT /evidence="ECO:0000256|SAM:SignalP, FT ECO:0000313|RefSeq:NP_705943.1" FT /id="PRO_5035036345" FT DOMAIN 20..58 FT /note="EGF-like" FT /evidence="ECO:0000259|PROSITE:PS50026" FT ACT_SITE 189 FT /note="Proton acceptor" FT /evidence="ECO:0000256|PIRSR:PIRSR619791-1" FT ACT_SITE 367 FT /note="For cyclooxygenase activity" FT /evidence="ECO:0000256|PIRSR:PIRSR619791-1" FT BINDING 109 FT /ligand="substrate" FT /evidence="ECO:0000256|PIRSR:PIRSR619791-2" FT BINDING 370 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:0000256|PIRSR:PIRSR619791-2" SQ SEQUENCE 601 AA; 68673 MW; A5852C56521DD0C1 CRC64; MNKLVCLVLL SSIWIFPGEG YDPCCAQPCQ NQGVCLSKGA DAYECDCTRT GYYGENCTTP ELLTRIKSAL KPRPNVVHHI LTHYKSIWDI INSISYLRDG IMRYILLSRS HLVESPPTYN ADYGYKSWEA YSNLSYYTRT LAPLPQNCPT PDLPNAKQVV EQVLLRKQFI PDPQRSSLMF AFFAQHFSHQ FFKSDFKKGP AFTKALGHGV DLGHIYGETL EVQHKLRLFK DGKLKYQVVD GEVYPPLVKD VQVEMHYPPH IPEEQKFAVG HEAFGLVPGL MMYATIWLRE HNRVCDIMKQ EHPDWDDERI FQTTRLILIG ETIKIVIEDY VQHLSGYNFK LKFDPELIFS ERFQYQNRIA AEFNTLYHWH PLLPDNFQIQ DQIYGYHQFV FNNSIVTTHG IRNMVDSFTK QTAGRVSGGR NLPPAVQGVA VKVLEQTRQM RYQSFNAYRR RFNMKPYSSF EEMTGDKDLA AQLKELYGHV DKVELYPGLL VEKSRPNSVF GETMVEMGAP YSLKGLMGNA ICSPEYWKPS TFGGKVGFDI VNSASLKKLV CLNISGPCPM VSFQVPDVKF QSSENVNSSS VHSTVNNINP TVVLNERSSE L //