GenomeNet

Database: UniProt/SWISS-PROT
Entry: PGH1_CANLF
LinkDB: PGH1_CANLF
Original site: PGH1_CANLF 
ID   PGH1_CANLF              Reviewed;         603 AA.
AC   Q8HZR1; F1PBX3; Q8HZR0;
DT   14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT   14-MAY-2014, sequence version 2.
DT   22-NOV-2017, entry version 112.
DE   RecName: Full=Prostaglandin G/H synthase 1;
DE            EC=1.14.99.1;
DE   AltName: Full=Cyclooxygenase-1;
DE            Short=COX-1;
DE   AltName: Full=Prostaglandin H2 synthase 1;
DE            Short=PGH synthase 1;
DE            Short=PGHS-1;
DE            Short=PHS 1;
DE   AltName: Full=Prostaglandin-endoperoxide synthase 1;
DE   Flags: Precursor;
GN   Name=PTGS1; Synonyms=COX1;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae;
OC   Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING,
RP   GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Brain cortex;
RX   PubMed=12242329; DOI=10.1073/pnas.162468699;
RA   Chandrasekharan N.V., Dai H., Roos K.L., Evanson N.K., Tomsik J.,
RA   Elton T.S., Simmons D.L.;
RT   "COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and
RT   other analgesic/antipyretic drugs: cloning, structure, and
RT   expression.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:13926-13931(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Boxer;
RX   PubMed=16341006; DOI=10.1038/nature04338;
RA   Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA   Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C.,
RA   Mauceli E., Xie X., Breen M., Wayne R.K., Ostrander E.A.,
RA   Ponting C.P., Galibert F., Smith D.R., deJong P.J., Kirkness E.F.,
RA   Alvarez P., Biagi T., Brockman W., Butler J., Chin C.-W., Cook A.,
RA   Cuff J., Daly M.J., DeCaprio D., Gnerre S., Grabherr M., Kellis M.,
RA   Kleber M., Bardeleben C., Goodstadt L., Heger A., Hitte C., Kim L.,
RA   Koepfli K.-P., Parker H.G., Pollinger J.P., Searle S.M.J.,
RA   Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA   Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA   Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L.,
RA   Bachantsang P., Barry A., Bayul T., Benamara M., Berlin A.,
RA   Bessette D., Blitshteyn B., Bloom T., Blye J., Boguslavskiy L.,
RA   Bonnet C., Boukhgalter B., Brown A., Cahill P., Calixte N.,
RA   Camarata J., Cheshatsang Y., Chu J., Citroen M., Collymore A.,
RA   Cooke P., Dawoe T., Daza R., Decktor K., DeGray S., Dhargay N.,
RA   Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L., Duffey N.,
RA   Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA   Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K.,
RA   Foley C., Franke A., Friedrich D., Gage D., Garber M., Gearin G.,
RA   Giannoukos G., Goode T., Goyette A., Graham J., Grandbois E.,
RA   Gyaltsen K., Hafez N., Hagopian D., Hagos B., Hall J., Healy C.,
RA   Hegarty R., Honan T., Horn A., Houde N., Hughes L., Hunnicutt L.,
RA   Husby M., Jester B., Jones C., Kamat A., Kanga B., Kells C.,
RA   Khazanovich D., Kieu A.C., Kisner P., Kumar M., Lance K., Landers T.,
RA   Lara M., Lee W., Leger J.-P., Lennon N., Leuper L., LeVine S., Liu J.,
RA   Liu X., Lokyitsang Y., Lokyitsang T., Lui A., Macdonald J., Major J.,
RA   Marabella R., Maru K., Matthews C., McDonough S., Mehta T.,
RA   Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T., Miller K.,
RA   Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A., Naylor J.,
RA   Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA   Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K.,
RA   Osman S., Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F.,
RA   Priest M., Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C.,
RA   Rege F., Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S.,
RA   Sharpe T., Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J.,
RA   Smith C., Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S.,
RA   Stone C., Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S.,
RA   Thoulutsang D., Thoulutsang Y., Topham K., Topping I., Tsamla T.,
RA   Vassiliev H., Venkataraman V., Vo A., Wangchuk T., Wangdi T.,
RA   Weiand M., Wilkinson J., Wilson A., Yadav S., Yang S., Yang X.,
RA   Young G., Yu Q., Zainoun J., Zembek L., Zimmer A., Lander E.S.;
RT   "Genome sequence, comparative analysis and haplotype structure of the
RT   domestic dog.";
RL   Nature 438:803-819(2005).
CC   -!- FUNCTION: Converts arachidonate to prostaglandin H2 (PGH2), a
CC       committed step in prostanoid synthesis. Involved in the
CC       constitutive production of prostanoids in particular in the
CC       stomach and platelets. In gastric epithelial cells, it is a key
CC       step in the generation of prostaglandins, such as prostaglandin E2
CC       (PGE2), which plays an important role in cytoprotection. In
CC       platelets, it is involved in the generation of thromboxane A2
CC       (TXA2), which promotes platelet activation and aggregation,
CC       vasoconstriction and proliferation of vascular smooth muscle cells
CC       (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY: Arachidonate + AH(2) + 2 O(2) = prostaglandin
CC       H(2) + A + H(2)O.
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   -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000250}; Peripheral
CC       membrane protein {ECO:0000269|PubMed:12242329}. Endoplasmic
CC       reticulum membrane {ECO:0000269|PubMed:12242329}; Peripheral
CC       membrane protein {ECO:0000269|PubMed:12242329}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=1; Synonyms=COX-1;
CC         IsoId=Q8HZR1-1; Sequence=Displayed;
CC       Name=2; Synonyms=COX-3;
CC         IsoId=Q8HZR1-2; Sequence=VSP_054856;
CC       Name=3; Synonyms=PCOX-1a;
CC         IsoId=Q8HZR1-3; Sequence=VSP_054856, VSP_054857;
CC         Note=No enzymatic activity. Membrane-bound.;
CC       Name=4; Synonyms=PCOX-1b;
CC         IsoId=Q8HZR1-4; Sequence=VSP_054857;
CC   -!- TISSUE SPECIFICITY: Brain cortex. Isoform 2 is expressed in the
CC       cerebral cortex and heart.
CC   -!- PTM: N-glycosylated. N-linked glycosylation is necessary for
CC       enzymatic activity. {ECO:0000269|PubMed:12242329}.
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}.
DR   EMBL; AF535138; AAN33049.1; -; mRNA.
DR   EMBL; AF535139; AAN38739.1; -; mRNA.
DR   EMBL; AAEX03006907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001003023.1; NM_001003023.2.
DR   UniGene; Cfa.61; -.
DR   SMR; Q8HZR1; -.
DR   STRING; 9615.ENSCAFP00000030067; -.
DR   BindingDB; Q8HZR1; -.
DR   ChEMBL; CHEMBL4133; -.
DR   PeroxiBase; 3362; CfaPGHS01.
DR   PaxDb; Q8HZR1; -.
DR   Ensembl; ENSCAFT00000032279; ENSCAFP00000030061; ENSCAFG00000020263. [Q8HZR1-3]
DR   Ensembl; ENSCAFT00000032287; ENSCAFP00000030067; ENSCAFG00000020263. [Q8HZR1-1]
DR   GeneID; 403544; -.
DR   KEGG; cfa:403544; -.
DR   CTD; 5742; -.
DR   eggNOG; KOG2408; Eukaryota.
DR   eggNOG; ENOG410XPZ3; LUCA.
DR   GeneTree; ENSGT00390000010743; -.
DR   HOGENOM; HOG000013149; -.
DR   HOVERGEN; HBG000366; -.
DR   KO; K00509; -.
DR   OMA; FKTSGKM; -.
DR   OrthoDB; EOG091G03CD; -.
DR   Reactome; R-CFA-140180; COX reactions.
DR   Reactome; R-CFA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR   UniPathway; UPA00662; -.
DR   Proteomes; UP000002254; Chromosome 9.
DR   Bgee; ENSCAFG00000020263; -.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR   GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0001750; C:photoreceptor outer segment; IEA:Ensembl.
DR   GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019371; P:cyclooxygenase pathway; IEA:Ensembl.
DR   GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR   GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0042127; P:regulation of cell proliferation; IEA:Ensembl.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR   Gene3D; 1.10.640.10; -; 1.
DR   InterPro; IPR029580; COX-1.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR010255; Haem_peroxidase.
DR   InterPro; IPR019791; Haem_peroxidase_animal.
DR   InterPro; IPR037120; Haem_peroxidase_sf.
DR   PANTHER; PTHR11903:SF6; PTHR11903:SF6; 1.
DR   Pfam; PF03098; An_peroxidase; 1.
DR   Pfam; PF00008; EGF; 1.
DR   PRINTS; PR00457; ANPEROXIDASE.
DR   SUPFAM; SSF48113; SSF48113; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   PROSITE; PS50292; PEROXIDASE_3; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Complete proteome; Dioxygenase; Disulfide bond;
KW   EGF-like domain; Endoplasmic reticulum; Fatty acid biosynthesis;
KW   Fatty acid metabolism; Glycoprotein; Heme; Iron; Lipid biosynthesis;
KW   Lipid metabolism; Membrane; Metal-binding; Microsome; Oxidoreductase;
KW   Peroxidase; Prostaglandin biosynthesis; Prostaglandin metabolism;
KW   Reference proteome; Signal.
FT   SIGNAL        1     27       {ECO:0000255}.
FT   CHAIN        28    603       Prostaglandin G/H synthase 1.
FT                                /FTId=PRO_0000429170.
FT   DOMAIN       35     73       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   ACT_SITE    210    210       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   ACT_SITE    388    388       For cyclooxygenase activity.
FT                                {ECO:0000250}.
FT   METAL       391    391       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   SITE        533    533       Aspirin-acetylated serine. {ECO:0000250}.
FT   CARBOHYD     71     71       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    107    107       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    147    147       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     39     50       {ECO:0000250}.
FT   DISULFID     40    162       {ECO:0000250}.
FT   DISULFID     44     60       {ECO:0000250}.
FT   DISULFID     62     72       {ECO:0000250}.
FT   DISULFID    572    578       {ECO:0000250}.
FT   VAR_SEQ       3      3       R -> REFDPEAPRNPLRLPGEPRMPGPALTSRSAG (in
FT                                isoform 2 and isoform 3).
FT                                {ECO:0000303|PubMed:12242329}.
FT                                /FTId=VSP_054856.
FT   VAR_SEQ     122    340       Missing (in isoform 3 and isoform 4).
FT                                {ECO:0000303|PubMed:12242329}.
FT                                /FTId=VSP_054857.
FT   CONFLICT    597    597       E -> Q (in Ref. 1; AAN33049/AAN38739).
FT                                {ECO:0000305}.
SQ   SEQUENCE   603 AA;  69305 MW;  435B3E3A3D5DCCA6 CRC64;
     MSRGSRLHRW PLLLLLLLLL PPPPVLPAEA RTPAPVNPCC YYPCQHQGIC VRFGLDRYQC
     DCTRTGYSGP NCTIPELWTW LRNSLRPSPS FLHFLLTHGR WFWEFINATF IRDMLMRLVL
     TARSNLIPSP PTYNIAHDYI SWESFSNVSY YTRVLPSVPQ DCPTPMGTKG KKQLPDAQLL
     GRRFLLRRKF IPDPQGTNLM FAFFAQHFTH QFFKTSGKMG PGFTKALGHG VDLGHIYGDN
     LDRQYQLRLF KDGKLKYQVL DGEMYPPSVE EAPVLMHYPR GILPQSQMAV GQEVFGLLPG
     LMLYATLWLR EHNRVCDLLK AEHPTWGDEQ LFQTARLILI GETIKIVIEE YVQQLSGYFL
     QLKFDPELLF SAQFQYRNRI AMEFNQLYHW HPLMPDSFWV GSQEYSYEQF LFNTSMLTHY
     GIEALVDAFS RQSAGRIGGG RNIDHHVLHV AVETIKESRE LRLQPFNEYR KRFGMRPYMS
     FQELTGEKEM AAELEELYGD IDALEFYPGL LLEKCHPNSI FGESMIEIGA PFSLKGLLGN
     PICSPEYWKP STFGGEMGFN MVKTATLKKL VCLNTKTCPY VSFRVPDPHQ DGGPGVERPS
     TEL
//
DBGET integrated database retrieval system