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Q8HZR1

- PGH1_CANFA

UniProt

Q8HZR1 - PGH1_CANFA

Protein

Prostaglandin G/H synthase 1

Gene

PTGS1

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 89 (01 Oct 2014)
      Sequence version 2 (14 May 2014)
      Previous versions | rss
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    Functioni

    Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells By similarity.By similarity

    Catalytic activityi

    Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.

    Cofactori

    Binds 1 heme B (iron-protoporphyrin IX) group per subunit.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei210 – 2101Proton acceptorPROSITE-ProRule annotation
    Active sitei388 – 3881For cyclooxygenase activityBy similarity
    Metal bindingi391 – 3911Iron (heme axial ligand)PROSITE-ProRule annotation
    Sitei533 – 5331Aspirin-acetylated serineBy similarity

    GO - Molecular functioni

    1. dioxygenase activity Source: UniProtKB-KW
    2. heme binding Source: InterPro
    3. metal ion binding Source: UniProtKB-KW
    4. peroxidase activity Source: UniProtKB-KW
    5. prostaglandin-endoperoxide synthase activity Source: UniProtKB-EC

    GO - Biological processi

    1. prostaglandin biosynthetic process Source: UniProtKB-UniPathway
    2. response to oxidative stress Source: InterPro

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase, Peroxidase

    Keywords - Biological processi

    Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_174506. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei3362. CfaPGHS01.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prostaglandin G/H synthase 1 (EC:1.14.99.1)
    Alternative name(s):
    Cyclooxygenase-1
    Short name:
    COX-1
    Prostaglandin H2 synthase 1
    Short name:
    PGH synthase 1
    Short name:
    PGHS-1
    Short name:
    PHS 1
    Prostaglandin-endoperoxide synthase 1
    Gene namesi
    Name:PTGS1
    Synonyms:COX1
    OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
    Taxonomic identifieri9615 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
    ProteomesiUP000002254: Chromosome 9

    Subcellular locationi

    Microsome membrane By similarity; Peripheral membrane protein 1 Publication. Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein 1 Publication

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2727Sequence AnalysisAdd
    BLAST
    Chaini28 – 603576Prostaglandin G/H synthase 1PRO_0000429170Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi39 ↔ 50By similarity
    Disulfide bondi40 ↔ 162By similarity
    Disulfide bondi44 ↔ 60By similarity
    Disulfide bondi62 ↔ 72By similarity
    Glycosylationi71 – 711N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi107 – 1071N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi147 – 1471N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi572 ↔ 578By similarity

    Post-translational modificationi

    N-glycosylated. N-linked glycosylation is necessary for enzymatic activity.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ8HZR0.

    Expressioni

    Tissue specificityi

    Brain cortex. Isoform 2 is expressed in the cerebral cortex and heart.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ8HZR1.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini35 – 7339EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the prostaglandin G/H synthase family.Curated
    Contains 1 EGF-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Signal

    Phylogenomic databases

    eggNOGiNOG39991.
    GeneTreeiENSGT00390000010743.
    HOGENOMiHOG000013149.
    HOVERGENiHBG000366.
    InParanoidiQ8HZR1.
    KOiK00509.

    Family and domain databases

    Gene3Di1.10.640.10. 1 hit.
    InterProiIPR029580. COX-1.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view]
    PANTHERiPTHR11903:SF6. PTHR11903:SF6. 1 hit.
    PfamiPF03098. An_peroxidase. 2 hits.
    [Graphical view]
    PRINTSiPR00457. ANPEROXIDASE.
    SMARTiSM00181. EGF. 1 hit.
    [Graphical view]
    SUPFAMiSSF48113. SSF48113. 1 hit.
    PROSITEiPS50026. EGF_3. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: Q8HZR1-1) [UniParc]FASTAAdd to Basket

    Also known as: COX-1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSRGSRLHRW PLLLLLLLLL PPPPVLPAEA RTPAPVNPCC YYPCQHQGIC    50
    VRFGLDRYQC DCTRTGYSGP NCTIPELWTW LRNSLRPSPS FLHFLLTHGR 100
    WFWEFINATF IRDMLMRLVL TARSNLIPSP PTYNIAHDYI SWESFSNVSY 150
    YTRVLPSVPQ DCPTPMGTKG KKQLPDAQLL GRRFLLRRKF IPDPQGTNLM 200
    FAFFAQHFTH QFFKTSGKMG PGFTKALGHG VDLGHIYGDN LDRQYQLRLF 250
    KDGKLKYQVL DGEMYPPSVE EAPVLMHYPR GILPQSQMAV GQEVFGLLPG 300
    LMLYATLWLR EHNRVCDLLK AEHPTWGDEQ LFQTARLILI GETIKIVIEE 350
    YVQQLSGYFL QLKFDPELLF SAQFQYRNRI AMEFNQLYHW HPLMPDSFWV 400
    GSQEYSYEQF LFNTSMLTHY GIEALVDAFS RQSAGRIGGG RNIDHHVLHV 450
    AVETIKESRE LRLQPFNEYR KRFGMRPYMS FQELTGEKEM AAELEELYGD 500
    IDALEFYPGL LLEKCHPNSI FGESMIEIGA PFSLKGLLGN PICSPEYWKP 550
    STFGGEMGFN MVKTATLKKL VCLNTKTCPY VSFRVPDPHQ DGGPGVERPS 600
    TEL 603
    Length:603
    Mass (Da):69,305
    Last modified:May 14, 2014 - v2
    Checksum:i435B3E3A3D5DCCA6
    GO
    Isoform 2 (identifier: Q8HZR1-2) [UniParc]FASTAAdd to Basket

    Also known as: COX-3

    The sequence of this isoform differs from the canonical sequence as follows:
         3-3: R → REFDPEAPRNPLRLPGEPRMPGPALTSRSAG

    Show »
    Length:633
    Mass (Da):72,504
    Checksum:iD338221B976BC6BE
    GO
    Isoform 3 (identifier: Q8HZR1-3) [UniParc]FASTAAdd to Basket

    Also known as: PCOX-1a

    The sequence of this isoform differs from the canonical sequence as follows:
         3-3: R → REFDPEAPRNPLRLPGEPRMPGPALTSRSAG
         122-340: Missing.

    Note: No enzymatic activity. Membrane-bound.

    Show »
    Length:414
    Mass (Da):47,512
    Checksum:i75B160CE739015AE
    GO
    Isoform 4 (identifier: Q8HZR1-4) [UniParc]FASTAAdd to Basket

    Also known as: PCOX-1b

    The sequence of this isoform differs from the canonical sequence as follows:
         122-340: Missing.

    Show »
    Length:384
    Mass (Da):44,313
    Checksum:i3545A960000ADF22
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti597 – 5971E → Q in AAN33049. (PubMed:12242329)Curated
    Sequence conflicti597 – 5971E → Q in AAN38739. (PubMed:12242329)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei3 – 31R → REFDPEAPRNPLRLPGEPRM PGPALTSRSAG in isoform 2 and isoform 3. 1 PublicationVSP_054856
    Alternative sequencei122 – 340219Missing in isoform 3 and isoform 4. 1 PublicationVSP_054857Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF535138 mRNA. Translation: AAN33049.1.
    AF535139 mRNA. Translation: AAN38739.1.
    AAEX03006907 Genomic DNA. No translation available.
    RefSeqiNP_001003023.1. NM_001003023.2.
    UniGeneiCfa.61.

    Genome annotation databases

    EnsembliENSCAFT00000032279; ENSCAFP00000030061; ENSCAFG00000020263. [Q8HZR1-3]
    ENSCAFT00000032287; ENSCAFP00000030067; ENSCAFG00000020263. [Q8HZR1-1]
    GeneIDi403544.
    KEGGicfa:403544.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF535138 mRNA. Translation: AAN33049.1 .
    AF535139 mRNA. Translation: AAN38739.1 .
    AAEX03006907 Genomic DNA. No translation available.
    RefSeqi NP_001003023.1. NM_001003023.2.
    UniGenei Cfa.61.

    3D structure databases

    ProteinModelPortali Q8HZR1.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    ChEMBLi CHEMBL4133.

    Protein family/group databases

    PeroxiBasei 3362. CfaPGHS01.

    Proteomic databases

    PaxDbi Q8HZR0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSCAFT00000032279 ; ENSCAFP00000030061 ; ENSCAFG00000020263 . [Q8HZR1-3 ]
    ENSCAFT00000032287 ; ENSCAFP00000030067 ; ENSCAFG00000020263 . [Q8HZR1-1 ]
    GeneIDi 403544.
    KEGGi cfa:403544.

    Organism-specific databases

    CTDi 5742.

    Phylogenomic databases

    eggNOGi NOG39991.
    GeneTreei ENSGT00390000010743.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    InParanoidi Q8HZR1.
    KOi K00509.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    Reactomei REACT_174506. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

    Miscellaneous databases

    NextBioi 20817054.

    Family and domain databases

    Gene3Di 1.10.640.10. 1 hit.
    InterProi IPR029580. COX-1.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view ]
    PANTHERi PTHR11903:SF6. PTHR11903:SF6. 1 hit.
    Pfami PF03098. An_peroxidase. 2 hits.
    [Graphical view ]
    PRINTSi PR00457. ANPEROXIDASE.
    SMARTi SM00181. EGF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48113. SSF48113. 1 hit.
    PROSITEi PS50026. EGF_3. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression."
      Chandrasekharan N.V., Dai H., Roos K.L., Evanson N.K., Tomsik J., Elton T.S., Simmons D.L.
      Proc. Natl. Acad. Sci. U.S.A. 99:13926-13931(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING, GLYCOSYLATION, SUBCELLULAR LOCATION.
      Tissue: Brain cortex.
    2. "Genome sequence, comparative analysis and haplotype structure of the domestic dog."
      Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B., Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E., Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F., Smith D.R.
      , deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W., Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S., Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A., Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P., Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A., Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P., Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P., Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B., Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A., Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M., Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S., Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L., Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S., Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C., Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G., Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N., Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A., Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A., Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M., Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L., LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A., Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S., Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T., Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A., Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N., Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S., Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M., Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F., Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T., Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C., Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C., Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D., Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H., Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J., Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J., Zembek L., Zimmer A., Lander E.S.
      Nature 438:803-819(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Boxer.

    Entry informationi

    Entry nameiPGH1_CANFA
    AccessioniPrimary (citable) accession number: Q8HZR1
    Secondary accession number(s): F1PBX3, Q8HZR0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 14, 2014
    Last sequence update: May 14, 2014
    Last modified: October 1, 2014
    This is version 89 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site.
    Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PGHS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PGHS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.
    PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3