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P35355

- PGH2_RAT

UniProt

P35355 - PGH2_RAT

Protein

Prostaglandin G/H synthase 2

Gene

Ptgs2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    Functioni

    Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.

    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. heme binding Source: UniProtKB
    2. lipid binding Source: RGD
    3. metal ion binding Source: UniProtKB-KW
    4. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: RGD
    5. peroxidase activity Source: UniProtKB-KW
    6. prostaglandin-endoperoxide synthase activity Source: UniProtKB
    7. protein binding Source: RGD

    GO - Biological processi

    1. anagen Source: Ensembl
    2. angiogenesis Source: RGD
    3. bone mineralization Source: MGI
    4. brown fat cell differentiation Source: Ensembl
    5. cellular response to ATP Source: RGD
    6. cellular response to hypoxia Source: Ensembl
    7. cellular response to mechanical stimulus Source: RGD
    8. cellular response to UV Source: RGD
    9. cyclooxygenase pathway Source: UniProtKB
    10. decidualization Source: RGD
    11. embryo implantation Source: RGD
    12. hair cycle Source: RGD
    13. inflammatory response Source: RGD
    14. learning Source: RGD
    15. maintenance of blood-brain barrier Source: RGD
    16. memory Source: RGD
    17. negative regulation of calcium ion transport Source: RGD
    18. negative regulation of cell cycle Source: RGD
    19. negative regulation of cell proliferation Source: RGD
    20. negative regulation of smooth muscle contraction Source: RGD
    21. negative regulation of synaptic transmission, dopaminergic Source: RGD
    22. ovulation Source: RGD
    23. positive regulation of apoptotic process Source: RGD
    24. positive regulation of brown fat cell differentiation Source: Ensembl
    25. positive regulation of cell death Source: RGD
    26. positive regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
    27. positive regulation of cell proliferation Source: RGD
    28. positive regulation of fever generation Source: BHF-UCL
    29. positive regulation of fibroblast growth factor production Source: BHF-UCL
    30. positive regulation of NF-kappaB import into nucleus Source: RGD
    31. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
    32. positive regulation of platelet-derived growth factor production Source: BHF-UCL
    33. positive regulation of smooth muscle cell proliferation Source: RGD
    34. positive regulation of smooth muscle contraction Source: RGD
    35. positive regulation of synaptic plasticity Source: RGD
    36. positive regulation of synaptic transmission, glutamatergic Source: RGD
    37. positive regulation of transforming growth factor beta production Source: BHF-UCL
    38. positive regulation of vasoconstriction Source: RGD
    39. positive regulation vascular endothelial growth factor production Source: BHF-UCL
    40. prostaglandin biosynthetic process Source: RGD
    41. regulation of blood pressure Source: UniProtKB
    42. response to cytokine Source: RGD
    43. response to drug Source: RGD
    44. response to estradiol Source: RGD
    45. response to fatty acid Source: RGD
    46. response to fructose Source: RGD
    47. response to glucocorticoid Source: RGD
    48. response to lipopolysaccharide Source: RGD
    49. response to lithium ion Source: RGD
    50. response to manganese ion Source: RGD
    51. response to organic cyclic compound Source: RGD
    52. response to organic substance Source: RGD
    53. response to organonitrogen compound Source: RGD
    54. response to oxidative stress Source: InterPro
    55. response to radiation Source: RGD
    56. response to tumor necrosis factor Source: RGD
    57. response to vitamin D Source: RGD
    58. sensory perception of pain Source: RGD

    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_194948. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    REACT_198846. Synthesis of 15-eicosatetraenoic acid derivatives.
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei3975. RnoPGHS02-A.

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 13

    Organism-specific databases

    RGDi620349. Ptgs2.

    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
    5. protein complex Source: RGD

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 17171 PublicationAdd
    BLAST
    Chaini18 – 604587Prostaglandin G/H synthase 2PRO_0000023879Add
    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

    Proteomic databases

    PaxDbiP35355.
    PRIDEiP35355.

    PTM databases

    PhosphoSiteiP35355.

    Expressioni

    Tissue specificityi

    Expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus.

    Inductioni

    By cytokines and mitogens.

    Gene expression databases

    GenevestigatoriP35355.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi248163. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliP35355.
    SMRiP35355. Positions 18-569.
    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.
    InParanoidiP35355.
    KOiK11987.
    OMAiICNNVKG.
    OrthoDBiEOG7RFTHC.
    PhylomeDBiP35355.
    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. 1 hit.
    [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.

    P35355-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLFRAVLLCA ALALSHAANP CCSNPCQNRG ECMSIGFDQY KCDCTRTGFY    50
    GENCTTPEFL TRIKLLLKPT PNTVHYILTH FKGVWNIVNN IPFLRNSIMR 100
    YVLTSRSHLI DSPPTYNVHY GYKSWEAFSN LSYYTRALPP VADDCPTPMG 150
    VKGNKELPDS KEVLEKVLLR REFIPDPQGT NMMFAFFAQH FTHQFFKTDQ 200
    KRGPGFTRGL GHGVDLNHVY GETLDRQHKL RLFQDGKLKY QVIGGEVYPP 250
    TVKDTQVDMI YPPHVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 300
    ILKQEHPEWD DERLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
    LLFNQQFQYQ NRIASEFNTL YHWHPLLPDT FNIEDQEYTF KQFLYNNSIL 400
    LEHGLAHFVE SFTRQIAGRV AGGRNVPIAV QAVAKASIDQ SREMKYQSLN 450
    EYRKRFSLKP YTSFEELTGE KEMAAELKAL YHDIDAMELY PALLVEKPRP 500
    DAIFGETMVE LGAPFSLKGL MGNPICSPQY WKPSTFGGEV GFRIINTASI 550
    QSLICNNVKG CPFASFNVQD PQPTKTATIN ASASHSRLDD INPTVLIKRR 600
    STEL 604
    Length:604
    Mass (Da):69,164
    Last modified:June 1, 1994 - v1
    Checksum:i98E418825D98FF0C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti11 – 133ALA → CPG(PubMed:8274023)Curated
    Sequence conflicti11 – 133ALA → CPG(PubMed:10816563)Curated
    Sequence conflicti58 – 581E → R(PubMed:8274023)Curated
    Sequence conflicti58 – 581E → R(PubMed:10816563)Curated
    Sequence conflicti66 – 661L → P(PubMed:8274023)Curated
    Sequence conflicti66 – 661L → P(PubMed:10816563)Curated
    Sequence conflicti96 – 983NSI → IQS(PubMed:8274023)Curated
    Sequence conflicti96 – 983NSI → IQS(PubMed:10816563)Curated
    Sequence conflicti339 – 3391S → R(PubMed:8274023)Curated
    Sequence conflicti339 – 3391S → R(PubMed:10816563)Curated
    Sequence conflicti344 – 3441K → Q(PubMed:8274023)Curated
    Sequence conflicti344 – 3441K → Q(PubMed:10816563)Curated
    Sequence conflicti350 – 3501E → D(PubMed:8274023)Curated
    Sequence conflicti350 – 3501E → D(PubMed:10816563)Curated
    Sequence conflicti368 – 3681N → K(PubMed:8274023)Curated
    Sequence conflicti368 – 3681N → K(PubMed:10816563)Curated
    Sequence conflicti573 – 5731P → A(PubMed:8274023)Curated
    Sequence conflicti573 – 5731P → A(PubMed:10816563)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L25925 mRNA. Translation: AAA16477.1.
    U04300 mRNA. Translation: AAA20246.1.
    U03389 mRNA. Translation: AAA03466.1.
    S67722 mRNA. Translation: AAB29401.1.
    AF233596 mRNA. Translation: AAF36986.1.
    PIRiJC2030.
    RefSeqiNP_058928.3. NM_017232.3.
    UniGeneiRn.217585.
    Rn.44369.

    Genome annotation databases

    EnsembliENSRNOT00000003567; ENSRNOP00000003567; ENSRNOG00000002525.
    GeneIDi29527.
    KEGGirno:29527.
    UCSCiRGD:620349. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L25925 mRNA. Translation: AAA16477.1 .
    U04300 mRNA. Translation: AAA20246.1 .
    U03389 mRNA. Translation: AAA03466.1 .
    S67722 mRNA. Translation: AAB29401.1 .
    AF233596 mRNA. Translation: AAF36986.1 .
    PIRi JC2030.
    RefSeqi NP_058928.3. NM_017232.3.
    UniGenei Rn.217585.
    Rn.44369.

    3D structure databases

    ProteinModelPortali P35355.
    SMRi P35355. Positions 18-569.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 248163. 1 interaction.

    Chemistry

    BindingDBi P35355.
    ChEMBLi CHEMBL2095157.

    Protein family/group databases

    PeroxiBasei 3975. RnoPGHS02-A.

    PTM databases

    PhosphoSitei P35355.

    Proteomic databases

    PaxDbi P35355.
    PRIDEi P35355.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000003567 ; ENSRNOP00000003567 ; ENSRNOG00000002525 .
    GeneIDi 29527.
    KEGGi rno:29527.
    UCSCi RGD:620349. rat.

    Organism-specific databases

    CTDi 5743.
    RGDi 620349. Ptgs2.

    Phylogenomic databases

    eggNOGi NOG39991.
    GeneTreei ENSGT00390000010743.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    InParanoidi P35355.
    KOi K11987.
    OMAi ICNNVKG.
    OrthoDBi EOG7RFTHC.
    PhylomeDBi P35355.
    TreeFami TF329675.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    Reactomei REACT_194948. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    REACT_198846. Synthesis of 15-eicosatetraenoic acid derivatives.

    Miscellaneous databases

    NextBioi 609492.
    PROi P35355.

    Gene expression databases

    Genevestigatori P35355.

    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. 1 hit.
    [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 and expression of rat prostaglandin endoperoxide synthase (cyclooxygenase)-2 cDNA."
      Kennedy B.P., Chan C.C., Culp S.A., Cromlish W.A.
      Biochem. Biophys. Res. Commun. 197:494-500(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids."
      Yamagata K., Andreasson K.I., Kaufmann W.E., Barnes C.A., Worley P.F.
      Neuron 11:371-386(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells."
      Dubois R.N., Tsujii M., Bishop P., Awad J.A., Makita K., Lanahan A.
      Am. J. Physiol. 266:G822-G827(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Wistar.
      Tissue: Intestine.
    4. "Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression."
      Feng L., Sun W., Xia Y., Tang W.W., Chanmugam P., Soyoola E., Wilson C.B., Hwang D.
      Arch. Biochem. Biophys. 307:361-368(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Fischer 344.
    5. "Immediate-early MEK-1-dependent stabilization of rat smooth muscle cell cyclooxygenase-2 mRNA by Galpha(q)-coupled receptor signaling."
      Xu K., Robida A.M., Murphy T.J.
      J. Biol. Chem. 275:23012-23019(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    6. "Purification and characterization of a novel, distinct isoform of prostaglandin endoperoxide synthase induced by human chorionic gonadotropin in granulosa cells of rat preovulatory follicles."
      Sirois J., Richards J.S.
      J. Biol. Chem. 267:6382-6388(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 18-43.
    7. "Cyclooxygenases: structural, cellular, and molecular biology."
      Smith W.L., DeWitt D.L., Garavito R.M.
      Annu. Rev. Biochem. 69:145-182(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
    8. "Aspirin, cyclooxygenase inhibition and colorectal cancer."
      Sostres C., Gargallo C.J., Lanas A.
      World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.

    Entry informationi

    Entry nameiPGH2_RAT
    AccessioniPrimary (citable) accession number: P35355
    Secondary accession number(s): Q64379, Q925V4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 143 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, Direct protein sequencing, 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