PGES2_MACFA
ID PGES2_MACFA Reviewed; 377 AA.
AC Q9N0A4; Q5DI73;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Prostaglandin E synthase 2;
DE EC=5.3.99.3 {ECO:0000269|PubMed:11866447, ECO:0000269|PubMed:23426368};
DE AltName: Full=Microsomal prostaglandin E synthase 2;
DE Short=mPGES-2;
DE Contains:
DE RecName: Full=Prostaglandin E synthase 2 truncated form;
GN Name=PTGES2; Synonyms=PGES2; ORFNames=QccE-11222;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=11866447; DOI=10.1006/bbrc.2002.6531;
RA Tanikawa N., Ohmiya Y., Ohkubo H., Hashimoto K., Kangawa K., Kojima M.,
RA Ito S., Watanabe K.;
RT "Identification and characterization of a novel type of membrane-associated
RT prostaglandin E synthase.";
RL Biochem. Biophys. Res. Commun. 291:884-889(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 163-247.
RX PubMed=15774546; DOI=10.1093/humrep/deh784;
RA Duffy D.M., Seachord C.L., Dozier B.L.;
RT "Microsomal prostaglandin E synthase-1 (mPGES-1) is the primary form of
RT PGES expressed by the primate periovulatory follicle.";
RL Hum. Reprod. 20:1485-1492(2005).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 88-377 IN COMPLEX WITH
RP INDOMETHACIN, AND SUBUNIT.
RX PubMed=15854652; DOI=10.1016/j.jmb.2005.03.035;
RA Yamada T., Komoto J., Watanabe K., Ohmiya Y., Takusagawa F.;
RT "Crystal structure and possible catalytic mechanism of microsomal
RT prostaglandin E synthase type 2 (mPGES-2).";
RL J. Mol. Biol. 348:1163-1176(2005).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 88-377 IN COMPLEX WITH HEME AND
RP GLUTATHIONE.
RX PubMed=17585783; DOI=10.1021/bi700605m;
RA Yamada T., Takusagawa F.;
RT "PGH2 degradation pathway catalyzed by GSH-heme complex bound microsomal
RT prostaglandin E2 synthase type 2: the first example of a dual-function
RT enzyme.";
RL Biochemistry 46:8414-8424(2007).
RN [6]
RP FUNCTION, HEME-BINDING, CATALYTIC ACTIVITY, AND CAUTION.
RX PubMed=23426368; DOI=10.1074/jbc.m112.418475;
RA Takusagawa F.;
RT "Microsomal prostaglandin E synthase type 2 (mPGES2) is a glutathione-
RT dependent heme protein, and dithiothreitol dissociates the bound heme to
RT produce active prostaglandin E2 synthase in vitro.";
RL J. Biol. Chem. 288:10166-10175(2013).
CC -!- FUNCTION: Isomerase that catalyzes the conversion of PGH2 into the more
CC stable prostaglandin E2 (PGE2) (in vitro) (PubMed:11866447,
CC PubMed:23426368). The biological function and the GSH-dependent
CC property of PTGES2 is still under debate (PubMed:23426368). In vivo,
CC PTGES2 could form a complex with GSH and heme and would not participate
CC in PGE2 synthesis but would catalyze the degradation of prostaglandin
CC E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid
CC (HHT) and malondialdehyde (MDA) (PubMed:23426368).
CC {ECO:0000269|PubMed:11866447, ECO:0000269|PubMed:23426368}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = prostaglandin E2; Xref=Rhea:RHEA:12893,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:606564; EC=5.3.99.3;
CC Evidence={ECO:0000269|PubMed:11866447, ECO:0000269|PubMed:23426368};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12894;
CC Evidence={ECO:0000305|PubMed:23426368};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = (12S)-hydroxy-(5Z,8E,10E)-
CC heptadecatrienoate + malonaldehyde; Xref=Rhea:RHEA:48644,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:90694, ChEBI:CHEBI:566274;
CC Evidence={ECO:0000269|PubMed:23426368};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48645;
CC Evidence={ECO:0000305|PubMed:23426368};
CC -!- ACTIVITY REGULATION: Isomerase activity is increased by sulfhydril
CC compounds. Dithiothreitol (DTT) is most effective, followed by
CC glutathione (GSH) and 2-mercaptoethanol. {ECO:0000269|PubMed:11866447}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=28 uM for PGH2 {ECO:0000269|PubMed:11866447};
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC {ECO:0000269|PubMed:11866447}.
CC -!- SUBUNIT: Homodimer (PubMed:15854652). May interact with CEBPB.
CC Interacts with EXOSC10 (By similarity). {ECO:0000250|UniProtKB:Q9H7Z7,
CC ECO:0000269|PubMed:15854652}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9H7Z7}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9H7Z7}.
CC -!- SUBCELLULAR LOCATION: [Prostaglandin E synthase 2 truncated form]:
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q9H7Z7}.
CC Note=Synthesized as a Golgi membrane-bound protein, which is further
CC cleaved into the predominant soluble truncated form. The truncated form
CC is cytoplasmic and is enriched in the perinuclear region.
CC {ECO:0000250|UniProtKB:Q9H7Z7}.
CC -!- PTM: Synthesized as a Golgi membrane-associated protein, and the
CC proteolytic removal of the N-terminal hydrophobic domain leads to the
CC formation of a mature cytosolic enzyme. {ECO:0000250|UniProtKB:Q9H7Z7}.
CC -!- SIMILARITY: Belongs to the GST superfamily. {ECO:0000305}.
CC -!- CAUTION: It is not known if heme and GST are required for prostaglandin
CC synthase activity. The protein copurifies with heme and GST when DTT is
CC omitted during the purification procedure. The GSH-heme complex-bound
CC enzyme has been proposed to act as a lyase and catalyze the degradation
CC of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-
CC heptadecatrienoic acid (HHT) and malondialdehyde (MDA) (By similarity).
CC Boiling the enzyme leads to loss of prostaglandin synthase activity,
CC but does not eliminate the lyase activity. Besides, free heme can
CC catalyze the formation of 12L-hydroxy-5,8,10-heptadecatrienoic acid
CC (HHT) (By similarity). A more recent study demonstrates the GSH-
CC dependent property of PTGES2, DTT dissociates the bound heme to produce
CC active PGE2 synthase in vitro (PubMed:23426368). PTGES2 can only
CC catalyzes PGE2 synthesis in the free state as an enzyme, while in vivo
CC it forms a complex with heme and does not participate in PGE2 synthesis
CC (PubMed:23426368). In agreement with this study, the in vivo evidence
CC from PTGES2 deficient mice do not show that this protein is responsible
CC for the PGE2 production under basal or pathophysiological conditions
CC (By similarity). {ECO:0000250|UniProtKB:Q8BWM0,
CC ECO:0000250|UniProtKB:Q9H7Z7, ECO:0000269|PubMed:23426368,
CC ECO:0000305}.
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DR EMBL; AB046026; BAB01608.1; -; mRNA.
DR EMBL; AB169647; BAE01728.1; -; mRNA.
DR EMBL; AY805118; AAW83056.1; -; mRNA.
DR PDB; 1Z9H; X-ray; 2.60 A; A/B/C/D=88-377.
DR PDB; 2PBJ; X-ray; 2.80 A; A/B/C/D=88-377.
DR PDBsum; 1Z9H; -.
DR PDBsum; 2PBJ; -.
DR AlphaFoldDB; Q9N0A4; -.
DR SMR; Q9N0A4; -.
DR STRING; 9541.XP_005582181.1; -.
DR eggNOG; KOG3029; Eukaryota.
DR BRENDA; 5.3.99.3; 1793.
DR SABIO-RK; Q9N0A4; -.
DR UniPathway; UPA00662; -.
DR EvolutionaryTrace; Q9N0A4; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0036134; F:12-hydroxyheptadecatrienoic acid synthase activity; IEA:RHEA.
DR GO; GO:0043295; F:glutathione binding; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0016829; F:lyase activity; IDA:UniProtKB.
DR GO; GO:0050220; F:prostaglandin-E synthase activity; IDA:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:InterPro.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB.
DR CDD; cd03197; GST_C_mPGES2; 1.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR004045; Glutathione_S-Trfase_N.
DR InterPro; IPR034334; PGES2.
DR InterPro; IPR034335; PGES2_C.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF13417; GST_N_3; 1.
DR SFLD; SFLDG01203; Prostaglandin_E_synthase_like1; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS00195; GLUTAREDOXIN_1; 1.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 1.
DR PROSITE; PS50405; GST_CTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism;
KW Golgi apparatus; Isomerase; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Phosphoprotein; Prostaglandin biosynthesis; Prostaglandin metabolism;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..377
FT /note="Prostaglandin E synthase 2"
FT /id="PRO_0000013129"
FT CHAIN 88..377
FT /note="Prostaglandin E synthase 2 truncated form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000013130"
FT CHAIN 89..375
FT /note="Prostaglandin E synthase 2 truncated form"
FT /evidence="ECO:0000250|UniProtKB:Q66LN0"
FT /id="PRO_0000451849"
FT TOPO_DOM 1..57
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..74
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 75..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 90..193
FT /note="Glutaredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT DOMAIN 263..377
FT /note="GST C-terminal"
FT BINDING 148
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:17585783"
FT BINDING 164..165
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:17585783"
FT SITE 87..88
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q66LN0"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7Z7"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:1Z9H"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:1Z9H"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:1Z9H"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:1Z9H"
FT STRAND 158..162
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 165..178
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:1Z9H"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:1Z9H"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:1Z9H"
FT TURN 206..209
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 215..221
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 225..240
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 246..250
FT /evidence="ECO:0007829|PDB:1Z9H"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 254..267
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 272..296
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 303..318
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 332..342
FT /evidence="ECO:0007829|PDB:1Z9H"
FT TURN 343..346
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 348..357
FT /evidence="ECO:0007829|PDB:1Z9H"
FT HELIX 360..371
FT /evidence="ECO:0007829|PDB:1Z9H"
SQ SEQUENCE 377 AA; 41916 MW; ADE6A2814D178D60 CRC64;
MAPATRVVRA LWTGGCALAW RLGGRPQPLL PTQSRAGFAG AAGGQGPVAA ARKGSPRLLG
AAALALGGAL GLYHTARWHL HAQDLHAERS AVQLSLSSRL QLTLYQYKTC PFCSKVRAFL
DFHALPYQVV EVNPVLRAEI KFSSYRKVPI LVAQEGESSQ QLNDSSVIIS ALKTYLVSGQ
PLEEIITYYP AMKAVNDQGK EVTEFGNKYW LMLNEKEAQQ VYSGKEARTE EMKWRQWADD
WLVHLISPNV YRTPTEALAS FDYIVREGKF GAVEGAVAKY MGAAAMYLIS KRLKSRHRLQ
DNVREDLYEA ADKWVAAVGK DRPFMGGQKP NLADLAVYGV LRVMEGLDAF DDLMQHTHIQ
PWYLRVERAI TEASPAH
