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Protein

Prostaglandin E synthase 2

Gene

PTGES2

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2).2 Publications

Catalytic activityi

(5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate.1 Publication

Enzyme regulationi

Isomerase activity is increased by sulfhydril compounds. Dithiothreitol (DTT) is most effective, followed by glutathione (GSH) and 2-mercaptoethanol.1 Publication

Kineticsi

  1. KM=28 µM for PGH21 Publication
  2. KM=56 µM for PGH2 (for the GSH-heme complex-bound enzyme)1 Publication

    Pathwayi: prostaglandin biosynthesis

    This protein is involved in the pathway prostaglandin biosynthesis, which is part of Lipid metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway prostaglandin biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei148 – 1481Glutathione; via amide nitrogen and carbonyl oxygen1 Publication

    GO - Molecular functioni

    • electron carrier activity Source: InterPro
    • glutathione binding Source: UniProtKB
    • heme binding Source: UniProtKB
    • lyase activity Source: UniProtKB
    • prostaglandin-E synthase activity Source: UniProtKB-EC
    • protein disulfide oxidoreductase activity Source: InterPro

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Isomerase

    Keywords - Biological processi

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

    Enzyme and pathway databases

    BRENDAi5.3.99.3. 1793.
    SABIO-RKQ9N0A4.
    UniPathwayiUPA00662.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prostaglandin E synthase 2 (EC:5.3.99.31 Publication)
    Alternative name(s):
    Microsomal prostaglandin E synthase 2
    Short name:
    mPGES-2
    Cleaved into the following chain:
    Gene namesi
    Name:PTGES2
    Synonyms:PGES2
    ORF Names:QccE-11222
    OrganismiMacaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
    Taxonomic identifieri9541 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca

    Subcellular locationi

    • Golgi apparatus membrane By similarity; Single-pass membrane protein By similarity
    Prostaglandin E synthase 2 truncated form :
    • Cytoplasmperinuclear region By similarity

    • Note: Synthesized as a Golgi membrane-bound protein, which is further cleaved into the predominant soluble truncated form. The truncated form is cytoplasmic and is enriched in the perinuclear region.By similarity

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 5757LumenalSequence analysisAdd
    BLAST
    Transmembranei58 – 7417HelicalSequence analysisAdd
    BLAST
    Topological domaini75 – 377303CytoplasmicSequence analysisAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Golgi apparatus, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi110 – 1101C → S: Can bind glutathione-heme and exhibits PGH2 degradation activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 377377Prostaglandin E synthase 2PRO_0000013129Add
    BLAST
    Chaini88 – 377290Prostaglandin E synthase 2 truncated formBy similarityPRO_0000013130Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei95 – 951PhosphoserineBy similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei87 – 882CleavageBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ9N0A4.

    Interactioni

    Subunit structurei

    May interact with CEBPB. Interacts with EXOSC10 (By similarity). Homodimer.By similarity2 Publications

    Structurei

    Secondary structure

    1
    377
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi101 – 1066Combined sources
    Helixi111 – 12212Combined sources
    Beta strandi127 – 1315Combined sources
    Turni134 – 1363Combined sources
    Helixi138 – 1403Combined sources
    Beta strandi150 – 1556Combined sources
    Beta strandi158 – 1625Combined sources
    Helixi165 – 17814Combined sources
    Helixi182 – 1854Combined sources
    Helixi186 – 1883Combined sources
    Beta strandi191 – 1955Combined sources
    Beta strandi201 – 2055Combined sources
    Turni206 – 2094Combined sources
    Helixi215 – 2217Combined sources
    Helixi225 – 24016Combined sources
    Helixi243 – 2453Combined sources
    Helixi246 – 2505Combined sources
    Beta strandi251 – 2533Combined sources
    Helixi254 – 26714Combined sources
    Helixi272 – 29625Combined sources
    Helixi303 – 31816Combined sources
    Helixi332 – 34211Combined sources
    Turni343 – 3464Combined sources
    Helixi348 – 35710Combined sources
    Helixi360 – 37112Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Z9HX-ray2.60A/B/C/D88-377[»]
    2PBJX-ray2.80A/B/C/D88-377[»]
    ProteinModelPortaliQ9N0A4.
    SMRiQ9N0A4. Positions 100-373.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9N0A4.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini90 – 193104GlutaredoxinPROSITE-ProRule annotationAdd
    BLAST
    Domaini263 – 377115GST C-terminalAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni164 – 1652Glutathione binding

    Sequence similaritiesi

    Belongs to the GST superfamily.Curated
    Contains 1 glutaredoxin domain.PROSITE-ProRule annotation
    Contains 1 GST C-terminal domain.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOVERGENiHBG069136.

    Family and domain databases

    Gene3Di1.20.1050.10. 2 hits.
    3.40.30.10. 1 hit.
    InterProiIPR002109. Glutaredoxin.
    IPR010987. Glutathione-S-Trfase_C-like.
    IPR004045. Glutathione_S-Trfase_N.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view]
    PfamiPF13417. GST_N_3. 1 hit.
    [Graphical view]
    SUPFAMiSSF47616. SSF47616. 1 hit.
    SSF52833. SSF52833. 1 hit.
    PROSITEiPS00195. GLUTAREDOXIN_1. 1 hit.
    PS51354. GLUTAREDOXIN_2. 1 hit.
    PS50405. GST_CTER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    Q9N0A4-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAPATRVVRA LWTGGCALAW RLGGRPQPLL PTQSRAGFAG AAGGQGPVAA
    60 70 80 90 100
    ARKGSPRLLG AAALALGGAL GLYHTARWHL HAQDLHAERS AVQLSLSSRL
    110 120 130 140 150
    QLTLYQYKTC PFCSKVRAFL DFHALPYQVV EVNPVLRAEI KFSSYRKVPI
    160 170 180 190 200
    LVAQEGESSQ QLNDSSVIIS ALKTYLVSGQ PLEEIITYYP AMKAVNDQGK
    210 220 230 240 250
    EVTEFGNKYW LMLNEKEAQQ VYSGKEARTE EMKWRQWADD WLVHLISPNV
    260 270 280 290 300
    YRTPTEALAS FDYIVREGKF GAVEGAVAKY MGAAAMYLIS KRLKSRHRLQ
    310 320 330 340 350
    DNVREDLYEA ADKWVAAVGK DRPFMGGQKP NLADLAVYGV LRVMEGLDAF
    360 370
    DDLMQHTHIQ PWYLRVERAI TEASPAH
    Length:377
    Mass (Da):41,916
    Last modified:October 1, 2000 - v1
    Checksum:iADE6A2814D178D60
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB046026 mRNA. Translation: BAB01608.1.
    AB169647 mRNA. Translation: BAE01728.1.
    AY805118 mRNA. Translation: AAW83056.1.
    UniGeneiMfa.2850.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB046026 mRNA. Translation: BAB01608.1.
    AB169647 mRNA. Translation: BAE01728.1.
    AY805118 mRNA. Translation: AAW83056.1.
    UniGeneiMfa.2850.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Z9HX-ray2.60A/B/C/D88-377[»]
    2PBJX-ray2.80A/B/C/D88-377[»]
    ProteinModelPortaliQ9N0A4.
    SMRiQ9N0A4. Positions 100-373.
    ModBaseiSearch...
    MobiDBiSearch...

    Proteomic databases

    PRIDEiQ9N0A4.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Phylogenomic databases

    HOVERGENiHBG069136.

    Enzyme and pathway databases

    UniPathwayiUPA00662.
    BRENDAi5.3.99.3. 1793.
    SABIO-RKQ9N0A4.

    Miscellaneous databases

    EvolutionaryTraceiQ9N0A4.

    Family and domain databases

    Gene3Di1.20.1050.10. 2 hits.
    3.40.30.10. 1 hit.
    InterProiIPR002109. Glutaredoxin.
    IPR010987. Glutathione-S-Trfase_C-like.
    IPR004045. Glutathione_S-Trfase_N.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view]
    PfamiPF13417. GST_N_3. 1 hit.
    [Graphical view]
    SUPFAMiSSF47616. SSF47616. 1 hit.
    SSF52833. SSF52833. 1 hit.
    PROSITEiPS00195. GLUTAREDOXIN_1. 1 hit.
    PS51354. GLUTAREDOXIN_2. 1 hit.
    PS50405. GST_CTER. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Identification and characterization of a novel type of membrane-associated prostaglandin E synthase."
      Tanikawa N., Ohmiya Y., Ohkubo H., Hashimoto K., Kangawa K., Kojima M., Ito S., Watanabe K.
      Biochem. Biophys. Res. Commun. 291:884-889(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
    2. "DNA sequences of macaque genes expressed in brain or testis and its evolutionary implications."
      International consortium for macaque cDNA sequencing and analysis
      Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain cortex.
    3. "Microsomal prostaglandin E synthase-1 (mPGES-1) is the primary form of PGES expressed by the primate periovulatory follicle."
      Duffy D.M., Seachord C.L., Dozier B.L.
      Hum. Reprod. 20:1485-1492(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 163-247.
    4. "Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2)."
      Yamada T., Komoto J., Watanabe K., Ohmiya Y., Takusagawa F.
      J. Mol. Biol. 348:1163-1176(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 88-377 IN COMPLEX WITH INDOMETHACIN, SUBUNIT.
    5. "PGH2 degradation pathway catalyzed by GSH-heme complex bound microsomal prostaglandin E2 synthase type 2: the first example of a dual-function enzyme."
      Yamada T., Takusagawa F.
      Biochemistry 46:8414-8424(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 88-377 IN COMPLEX WITH HEME AND GLUTATHIONE, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, MUTAGENESIS OF CYS-110.

    Entry informationi

    Entry nameiPGES2_MACFA
    AccessioniPrimary (citable) accession number: Q9N0A4
    Secondary accession number(s): Q5DI73
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 30, 2005
    Last sequence update: October 1, 2000
    Last modified: July 6, 2016
    This is version 90 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    Heme and GST are not required for prostaglandin synthase activity, but the protein copurifies with heme and GST when DTT is omitted during the purification procedure. According to PubMed:17585783, the GSH-heme complex-bound enzyme (mPGES-2h) may act as a lyase and catalyze the degradation of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid (HHT) and malondialdehyde (MDA), but experiments done with the human enzyme suggest that this activity is spurious and that the reaction is catalyzed by heme, since free heme can efficiently catalyze the formation of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT).Curated

    Keywords - Technical termi

    3D-structure

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.