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Database: UniProt/SWISS-PROT
Entry: PGH1_MOUSE
LinkDB: PGH1_MOUSE
Original site: PGH1_MOUSE 
ID   PGH1_MOUSE              Reviewed;         602 AA.
AC   P22437;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1991, sequence version 1.
DT   13-FEB-2019, entry version 183.
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=Cox-1, Cox1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2108169;
RA   Dewitt D.L., El-Harith E.A., Kraemer S.A., Andrews M.J., Yao E.F.,
RA   Armstrong R.L., Smith W.L.;
RT   "The aspirin and heme-binding sites of ovine and murine prostaglandin
RT   endoperoxide synthases.";
RL   J. Biol. Chem. 265:5192-5198(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
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   [3]
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, Liver, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
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. 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
CC       cells.
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   -!- 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.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane
CC       protein. Endoplasmic reticulum membrane; Peripheral membrane
CC       protein.
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; M34141; AAA39913.1; -; mRNA.
DR   EMBL; BC005573; AAH05573.1; -; mRNA.
DR   CCDS; CCDS15970.1; -.
DR   PIR; A35564; A35564.
DR   RefSeq; NP_032995.1; NM_008969.4.
DR   RefSeq; XP_006497853.1; XM_006497790.3.
DR   RefSeq; XP_006497854.1; XM_006497791.3.
DR   RefSeq; XP_011237338.1; XM_011239036.2.
DR   RefSeq; XP_017171985.1; XM_017316496.1.
DR   UniGene; Mm.275434; -.
DR   ProteinModelPortal; P22437; -.
DR   SMR; P22437; -.
DR   BioGrid; 202462; 2.
DR   IntAct; P22437; 3.
DR   MINT; P22437; -.
DR   STRING; 10090.ENSMUSP00000059977; -.
DR   BindingDB; P22437; -.
DR   ChEMBL; CHEMBL2649; -.
DR   PeroxiBase; 3361; MmPGHS01.
DR   PhosphoSitePlus; P22437; -.
DR   PaxDb; P22437; -.
DR   PeptideAtlas; P22437; -.
DR   PRIDE; P22437; -.
DR   Ensembl; ENSMUST00000062069; ENSMUSP00000059977; ENSMUSG00000047250.
DR   GeneID; 19224; -.
DR   KEGG; mmu:19224; -.
DR   UCSC; uc008jll.2; mouse.
DR   CTD; 5742; -.
DR   MGI; MGI:97797; Ptgs1.
DR   eggNOG; KOG2408; Eukaryota.
DR   eggNOG; ENOG410XPZ3; LUCA.
DR   GeneTree; ENSGT00390000010743; -.
DR   HOGENOM; HOG000013149; -.
DR   HOVERGEN; HBG000366; -.
DR   InParanoid; P22437; -.
DR   KO; K00509; -.
DR   OMA; MPDSFKV; -.
DR   OrthoDB; 324380at2759; -.
DR   PhylomeDB; P22437; -.
DR   TreeFam; TF329675; -.
DR   Reactome; R-MMU-140180; COX reactions.
DR   Reactome; R-MMU-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR   UniPathway; UPA00662; -.
DR   ChiTaRS; Ptgs1; mouse.
DR   PRO; PR:P22437; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   Bgee; ENSMUSG00000047250; Expressed in 264 organ(s), highest expression level in uterus.
DR   ExpressionAtlas; P22437; baseline and differential.
DR   Genevisible; P22437; MM.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR   GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0001750; C:photoreceptor outer segment; IDA:MGI.
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; ISO:MGI.
DR   GO; GO:0019371; P:cyclooxygenase pathway; ISO:MGI.
DR   GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR   GO; GO:0030216; P:keratinocyte differentiation; NAS:UniProtKB.
DR   GO; GO:0007612; P:learning; ISO:MGI.
DR   GO; GO:0035633; P:maintenance of permeability of blood-brain barrier; ISO:MGI.
DR   GO; GO:0007613; P:memory; ISO:MGI.
DR   GO; GO:0097756; P:negative regulation of blood vessel diameter; ISO:MGI.
DR   GO; GO:0032811; P:negative regulation of epinephrine secretion; ISO:MGI.
DR   GO; GO:0010700; P:negative regulation of norepinephrine secretion; ISO:MGI.
DR   GO; GO:0045987; P:positive regulation of smooth muscle contraction; ISO:MGI.
DR   GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; IMP:MGI.
DR   GO; GO:0006693; P:prostaglandin metabolic process; IMP:MGI.
DR   GO; GO:0008217; P:regulation of blood pressure; IMP:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR   GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR   Gene3D; 1.10.640.10; -; 1.
DR   InterPro; IPR029580; COX-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:SF6; PTHR11903:SF6; 1.
DR   Pfam; PF03098; An_peroxidase; 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   Complete proteome; Dioxygenase; Disulfide bond; EGF-like domain;
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   Prostaglandin biosynthesis; Prostaglandin metabolism;
KW   Reference proteome; Signal.
FT   SIGNAL        1     26
FT   CHAIN        27    602       Prostaglandin G/H synthase 1.
FT                                /FTId=PRO_0000023869.
FT   DOMAIN       34     72       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   ACT_SITE    209    209       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   ACT_SITE    387    387       For cyclooxygenase activity.
FT                                {ECO:0000250}.
FT   METAL       390    390       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   SITE        532    532       Aspirin-acetylated serine.
FT   CARBOHYD     70     70       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    106    106       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    146    146       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     38     49       {ECO:0000250}.
FT   DISULFID     39    161       {ECO:0000250}.
FT   DISULFID     43     59       {ECO:0000250}.
FT   DISULFID     61     71       {ECO:0000250}.
FT   DISULFID    571    577       {ECO:0000250}.
SQ   SEQUENCE   602 AA;  69042 MW;  634C0E602045C3A0 CRC64;
     MSRRSLSLWF PLLLLLLLPP TPSVLLADPG VPSPVNPCCY YPCQNQGVCV RFGLDNYQCD
     CTRTGYSGPN CTIPEIWTWL RNSLRPSPSF THFLLTHGYW LWEFVNATFI REVLMRLVLT
     VRSNLIPSPP TYNSAHDYIS WESFSNVSYY TRILPSVPKD CPTPMGTKGK KQLPDVQLLA
     QQLLLRREFI PAPQGTNILF AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDNL
     ERQYHLRLFK DGKLKYQVLD GEVYPPSVEQ ASVLMRYPPG VPPERQMAVG QEVFGLLPGL
     MLFSTIWLRE HNRVCDLLKE EHPTWDDEQL FQTTRLILIG ETIKIVIEEY VQHLSGYFLQ
     LKFDPELLFR AQFQYRNRIA MEFNHLYHWH PLMPNSFQVG SQEYSYEQFL FNTSMLVDYG
     VEALVDAFSR QRAGRIGGGR NFDYHVLHVA VDVIKESREM RLQPFNEYRK RFGLKPYTSF
     QELTGEKEMA AELEELYGDI DALEFYPGLL LEKCQPNSIF GESMIEMGAP FSLKGLLGNP
     ICSPEYWKPS TFGGDVGFNL VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVLVRRST
     EL
//
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