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O02768

- PGH2_RABIT

UniProt

O02768 - PGH2_RABIT

Protein

Prostaglandin G/H synthase 2

Gene

PTGS2

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      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
    Binding sitei106 – 1061SubstrateBy similarity
    Active sitei193 – 1931Proton acceptorPROSITE-ProRule annotation
    Binding sitei341 – 3411SubstrateBy similarity
    Active sitei371 – 3711For cyclooxygenase activityBy similarity
    Binding sitei371 – 3711SubstrateBy similarity
    Metal bindingi374 – 3741Iron (heme axial ligand)PROSITE-ProRule annotation
    Sitei516 – 5161Aspirin-acetylated serineBy similarity

    GO - Molecular functioni

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

    GO - Biological processi

    1. anagen Source: Ensembl
    2. brown fat cell differentiation Source: Ensembl
    3. cellular response to hypoxia Source: Ensembl
    4. cyclooxygenase pathway Source: UniProtKB
    5. positive regulation of brown fat cell differentiation Source: Ensembl
    6. positive regulation of fever generation Source: Ensembl
    7. prostaglandin biosynthetic process Source: UniProtKB
    8. regulation of blood pressure Source: UniProtKB
    9. regulation of cell proliferation Source: Ensembl
    10. 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

    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei4130. OcuPGHS02.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prostaglandin G/H synthase 2 (EC:1.14.99.1)
    Alternative name(s):
    Cyclooxygenase-2
    Short name:
    COX-2
    PHS II
    Prostaglandin H2 synthase 2
    Short name:
    PGH synthase 2
    Short name:
    PGHS-2
    Prostaglandin-endoperoxide synthase 2
    Gene namesi
    Name:PTGS2
    Synonyms:COX-2, COX2
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    ProteomesiUP000001811: Chromosome 16

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. neuron projection Source: Ensembl
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717By similarityAdd
    BLAST
    Chaini18 – 604587Prostaglandin G/H synthase 2PRO_0000023878Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi21 ↔ 32By similarity
    Disulfide bondi22 ↔ 145By similarity
    Disulfide bondi26 ↔ 42By similarity
    Disulfide bondi44 ↔ 54By similarity
    Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi396 – 3961N-linked (GlcNAc...)Sequence Analysis
    Modified residuei526 – 5261S-nitrosocysteineBy similarity
    Disulfide bondi555 ↔ 561By similarity
    Glycosylationi580 – 5801N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526 By similarity.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, S-nitrosylation

    Expressioni

    Tissue specificityi

    Highest expression in kidney and urinary bladder.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    STRINGi9986.ENSOCUP00000014415.

    Structurei

    3D structure databases

    ProteinModelPortaliO02768.
    SMRiO02768. Positions 18-568.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini18 – 5538EGF-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

    Signal

    Phylogenomic databases

    eggNOGiNOG39991.
    GeneTreeiENSGT00390000010743.
    HOGENOMiHOG000013149.
    HOVERGENiHBG000366.
    OMAiICNNVKG.
    OrthoDBiEOG7RFTHC.
    TreeFamiTF329675.

    Family and domain databases

    Gene3Di1.10.640.10. 1 hit.
    InterProiIPR029576. COX-2.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view]
    PANTHERiPTHR11903:SF8. PTHR11903:SF8. 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]

    Sequencei

    Sequence statusi: Complete.

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

    O02768-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLARALLLCA AVALSHAANP CCSNPCQNRG VCMTMGFDQY KCDCTRTGFY    50
    GENCSTPEFL TRIKLLLKPT PDTVHYILTH FKGVWNIVNS IPFLRNSIMK 100
    YVLTSRSHMI DSPPTYNVHY NYKSWEAFSN LSYYTRALPP VADDCPTPMG 150
    VKGKKELPDS KDVVEKLLLR RKFIPDPQGT NMMFAFFAQH FTHQFFKTDL 200
    KRGPAFTKGL GHGVDLNHIY GETLDRQHKL RLFKDGKMKY QVIDGEVYPP 250
    TVKDTQVEMI YPPHIPAHLQ FAVGQEVFGL VPGLMMYATI WLREHNRVCD 300
    VLKQEHPEWD DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
    LLFNQQFQYQ NRIAAEFNTL YHWHPLLPDT FQIDDQQYNY QQFLYNNSIL 400
    LEHGLTQFVE SFTRQIAGRV AGGRNVPPAV QKVAKASIDQ SRQMKYQSLN 450
    EYRKRFLLKP YESFEELTGE KEMAAELEAL YGDIDAVELY PALLVERPRP 500
    DAIFGESMVE MGAPFSLKGL MGNPICSPNY WKPSTFGGEV GFKIVNTASI 550
    QSLICNNVKG CPFTSFNVPD PQLTKTVTIN ASASHSRLED INPTVLLKGR 600
    STEL 604
    Length:604
    Mass (Da):69,007
    Last modified:July 1, 1997 - v1
    Checksum:iC52F9F5BC1F493D7
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U97696 mRNA. Translation: AAB71222.1.
    RefSeqiNP_001075857.1. NM_001082388.1.
    UniGeneiOcu.2173.

    Genome annotation databases

    EnsembliENSOCUT00000016770; ENSOCUP00000014415; ENSOCUG00000016771.
    GeneIDi100009248.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U97696 mRNA. Translation: AAB71222.1 .
    RefSeqi NP_001075857.1. NM_001082388.1.
    UniGenei Ocu.2173.

    3D structure databases

    ProteinModelPortali O02768.
    SMRi O02768. Positions 18-568.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9986.ENSOCUP00000014415.

    Chemistry

    BindingDBi O02768.
    ChEMBLi CHEMBL1293198.

    Protein family/group databases

    PeroxiBasei 4130. OcuPGHS02.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSOCUT00000016770 ; ENSOCUP00000014415 ; ENSOCUG00000016771 .
    GeneIDi 100009248.

    Organism-specific databases

    CTDi 5743.

    Phylogenomic databases

    eggNOGi NOG39991.
    GeneTreei ENSGT00390000010743.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    OMAi ICNNVKG.
    OrthoDBi EOG7RFTHC.
    TreeFami TF329675.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .

    Family and domain databases

    Gene3Di 1.10.640.10. 1 hit.
    InterProi IPR029576. COX-2.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view ]
    PANTHERi PTHR11903:SF8. PTHR11903:SF8. 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. "Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells."
      Guan Y., Chang M., Cho W., Zhang Y., Redha R., Davis L., Chang S., Dubois R.N., Hao C.M., Breyer M.
      Am. J. Physiol. 273:F18-F26(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: New Zealand white.

    Entry informationi

    Entry nameiPGH2_RABIT
    AccessioniPrimary (citable) accession number: O02768
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 117 of the entry and version 1 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