PGES2_BOVIN
ID PGES2_BOVIN Reviewed; 372 AA.
AC Q66LN0; F1N1J6;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 3.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Prostaglandin E synthase 2;
DE EC=5.3.99.3 {ECO:0000269|PubMed:10446427, ECO:0000269|PubMed:11866447};
DE AltName: Full=Membrane-associated prostaglandin E synthase-2 {ECO:0000303|PubMed:10446427};
DE Short=mPGE synthase-2 {ECO:0000303|PubMed:10446427};
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP PROTEIN SEQUENCE OF 85-106, CATALYTIC ACTIVITY, FUNCTION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 135-191, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=15744024; DOI=10.1095/biolreprod.104.037036;
RA Parent J., Fortier M.A.;
RT "Expression and contribution of three different isoforms of prostaglandin E
RT synthase in the bovine endometrium.";
RL Biol. Reprod. 73:36-44(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10446427; DOI=10.1016/s1388-1981(99)00084-0;
RA Watanabe K., Kurihara K., Suzuki T.;
RT "Purification and characterization of membrane-bound prostaglandin E
RT synthase from bovine heart.";
RL Biochim. Biophys. Acta 1439:406-414(1999).
CC -!- FUNCTION: Isomerase that catalyzes the conversion of PGH2 into the more
CC stable prostaglandin E2 (PGE2) (in vitro) (PubMed:10446427,
CC PubMed:11866447). The biological function and the GSH-dependent
CC property of PTGES2 is still under debate (By similarity). 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) (By similarity).
CC {ECO:0000250|UniProtKB:Q9H7Z7, ECO:0000250|UniProtKB:Q9N0A4,
CC ECO:0000269|PubMed:10446427, ECO:0000269|PubMed:11866447}.
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:10446427, ECO:0000269|PubMed:11866447};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12894;
CC Evidence={ECO:0000305|PubMed:19393038};
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:0000250|UniProtKB:Q9H7Z7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48645;
CC Evidence={ECO:0000250|UniProtKB:Q9H7Z7};
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:10446427}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=28 uM for PGH2 {ECO:0000269|PubMed:11866447};
CC KM=24 uM for PGH2 {ECO:0000269|PubMed:10446427};
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC {ECO:0000269|PubMed:10446427, ECO:0000269|PubMed:11866447}.
CC -!- SUBUNIT: May interact with CEBPB. Interacts with EXOSC10 (By
CC similarity). Homodimer. {ECO:0000250|UniProtKB:Q8BWM0,
CC ECO:0000250|UniProtKB:Q9H7Z7}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:10446427};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Prostaglandin E synthase 2 truncated form]:
CC Cytoplasm {ECO:0000250|UniProtKB:Q9H7Z7}. Note=Synthesized as a Golgi
CC membrane-bound protein, which is further cleaved into the predominant
CC soluble truncated form. {ECO:0000250|UniProtKB:Q9H7Z7}.
CC -!- TISSUE SPECIFICITY: Detected in heart (at protein level)
CC (PubMed:10446427). Widely expressed. Expressed in heart > kidney >
CC muscle > testis > endometrium = ovary > myometrium = spleen = lung. In
CC endometrium, it is mainly expressed in luminal epithelial cells
CC followed by glandular epithelial cells, but expression is also present
CC in stromal cells at a lower level. {ECO:0000269|PubMed:10446427,
CC ECO:0000269|PubMed:15744024}.
CC -!- DEVELOPMENTAL STAGE: During the estrus cycle, it decreases from the
CC beginning of the cycle until days 13-15 and then increase until
CC ovulation (at protein level). {ECO:0000269|PubMed:15744024}.
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). Boiling the
CC enzyme leads to loss of prostaglandin synthase activity, but does not
CC eliminate the lyase activity. Besides, free heme can catalyze the
CC formation of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) (By
CC similarity). A more recent study demonstrates the GSH-dependent
CC property of PTGES2, DTT dissociates the bound heme to produce active
CC PGE2 synthase in vitro (By similarity). PTGES2 can only catalyzes PGE2
CC synthesis in the free state as an enzyme, while in vivo it forms a
CC complex with heme and does not participate in PGE2 synthesis (By
CC similarity). In agreement with this study, the in vivo evidence from
CC PTGES2 deficient mice do not show that this protein is responsible for
CC the PGE2 production under basal or pathophysiological conditions (By
CC similarity). {ECO:0000250|UniProtKB:Q8BWM0,
CC ECO:0000250|UniProtKB:Q9H7Z7, ECO:0000250|UniProtKB:Q9N0A4,
CC ECO:0000305}.
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DR EMBL; DAAA02032171; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY692441; AAU04848.1; -; mRNA.
DR RefSeq; NP_001160026.1; NM_001166554.1.
DR AlphaFoldDB; Q66LN0; -.
DR SMR; Q66LN0; -.
DR STRING; 9913.ENSBTAP00000021584; -.
DR PaxDb; Q66LN0; -.
DR PRIDE; Q66LN0; -.
DR GeneID; 493639; -.
DR KEGG; bta:493639; -.
DR CTD; 80142; -.
DR eggNOG; KOG3029; Eukaryota.
DR InParanoid; Q66LN0; -.
DR OrthoDB; 1042777at2759; -.
DR TreeFam; TF314304; -.
DR BRENDA; 5.3.99.3; 908.
DR UniPathway; UPA00662; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0036134; F:12-hydroxyheptadecatrienoic acid synthase activity; IEA:RHEA.
DR GO; GO:0043295; F:glutathione binding; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0016829; F:lyase activity; ISS: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 Cytoplasm; Direct protein sequencing; Endoplasmic reticulum;
KW Fatty acid biosynthesis; Fatty acid metabolism; Isomerase;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Microsome; Phosphoprotein;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..372
FT /note="Prostaglandin E synthase 2"
FT /id="PRO_0000013125"
FT CHAIN 86..372
FT /note="Prostaglandin E synthase 2 truncated form"
FT /evidence="ECO:0000269|PubMed:11866447"
FT /id="PRO_0000013126"
FT TOPO_DOM 1..54
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 55..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 72..372
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 87..190
FT /note="Glutaredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT DOMAIN 259..372
FT /note="GST C-terminal"
FT BINDING 145
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:Q9N0A4"
FT BINDING 161..162
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:Q9N0A4"
FT SITE 84..85
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:11866447"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H7Z7"
SQ SEQUENCE 372 AA; 41738 MW; A87152D6CA33CD22 CRC64;
MAHAVRALWP HGRALAWRLG DRPALGLHAQ SRAGFTGAAG GSGPAATARK GGPRLLGAAA
LALGGALGLY HTARWHLRAQ DLRAERSATQ LSLSSRLQLT LYQYKTCPFC SKVRAFLDFH
ALPYQVVEVN PVRRAEIKFS SYRKVPIVMA QEGESLQQLN DSSVIISALK TYLVSGQPLA
DIITYYPPMK AVNDQGKEVT EFCNKYWLML DEKEAQRMYG GKEARTEEMK WRQWADDWLV
HLISPNVYRT PAEALASFDY IVKEGNFGTV EGAMAKYMGA AAMYFISKRL KRRHHLRDDV
REDLYEAANK WVAAVGKDRP FMGGQKPNLA DLAVYGVLRV MEGLEAFDDL MRHTHIQPWY
LRVEKAIAEA PQ
