UniProtKB - O14684 (PTGES_HUMAN)
Protein
Prostaglandin E synthase
Gene
PTGES
Organism
Homo sapiens (Human)
Status
Functioni
Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway. Catalyzes the glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli (PubMed:18682561, PubMed:10377395, PubMed:12672824, PubMed:12460774, PubMed:10869354, PubMed:12244105). Plays a key role in inflammation response, fever and pain (By similarity). Catalyzes also the oxidoreduction of endocannabinoids into prostaglandin glycerol esters and PGG2 into 15-hydroperoxy-PGE2 (PubMed:12244105, PubMed:12672824). In addition, displays low glutathione transferase and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively (PubMed:12672824).By similarity6 Publications
Catalytic activityi
- EC:5.3.99.39 PublicationsThis reaction proceeds in the forward4 Publications direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- 1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-S-glutathione + chloride + H+2 PublicationsEC:2.5.1.182 PublicationsThis reaction proceeds in the forward1 Publication direction.
Cofactori
glutathione5 Publications
Activity regulationi
Induced by interleukin IL1B.1 Publication
Kineticsi
kcat is 50 sec(-1) for prostaglandin H2 as substrate (PubMed:12672824). kcat is 75 sec(-1) for prostaglandin H2 as substrate (PubMed:12672824). kcat is 21 sec(-1) for glutathione as substrate (PubMed:12672824).1 Publication
- KM=75 µM for glutathione1 Publication
- KM=160 µM for prostaglandin H2 (at 37 degrees)1 Publication
- KM=71 µM for glutathione (at 37 degrees)1 Publication
- KM=160 µM for prostaglandin G2 (at 37 degrees)1 Publication
- KM=14 µM for prostaglandin H21 Publication
- KM=130 µM for prostaglandin H21 Publication
- Vmax=170 µmol/min/mg enzyme with prostaglandin H2 as substrate1 Publication
: prostaglandin biosynthesis Pathwayi
This protein is involved in the pathway prostaglandin biosynthesis, which is part of Lipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway prostaglandin biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 38 | GlutathioneCombined sources2 Publications | 1 | |
Sitei | 49 | Essential for protaglandin-E synthase activity2 Publications | 1 | |
Binding sitei | 113 | GlutathioneCombined sources2 Publications | 1 | |
Binding sitei | 117 | GlutathioneCombined sources2 Publications | 1 | |
Sitei | 126 | Essential for protaglandin-E synthase activity2 Publications | 1 |
GO - Molecular functioni
- glutathione binding Source: UniProtKB
- glutathione peroxidase activity Source: UniProtKB
- glutathione transferase activity Source: UniProtKB
- prostaglandin-D synthase activity Source: Ensembl
- prostaglandin-E synthase activity Source: UniProtKB
GO - Biological processi
- acute inflammatory response Source: Ensembl
- chronic inflammatory response Source: Ensembl
- cyclooxygenase pathway Source: Reactome
- negative regulation of cell population proliferation Source: Ensembl
- oxidation-reduction process Source: GO_Central
- positive regulation of prostaglandin secretion Source: Ensembl
- prostaglandin biosynthetic process Source: UniProtKB
- prostaglandin metabolic process Source: ProtInc
- regulation of fever generation Source: UniProtKB
- regulation of inflammatory response Source: UniProtKB
- response to calcium ion Source: Ensembl
- response to cytokine Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- response to organic cyclic compound Source: Ensembl
- response to retinoic acid Source: Ensembl
- sensory perception of pain Source: UniProtKB
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Isomerase, Oxidoreductase, Transferase |
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism |
Enzyme and pathway databases
BioCyci | MetaCyc:HS07518-MONOMER |
BRENDAi | 5.3.99.3, 2681 |
PathwayCommonsi | O14684 |
Reactomei | R-HSA-2162123, Synthesis of Prostaglandins (PG) and Thromboxanes (TX) |
SABIO-RKi | O14684 |
SIGNORi | O14684 |
UniPathwayi | UPA00662 |
Chemistry databases
SwissLipidsi | SLP:000001631 |
Names & Taxonomyi
Protein namesi | Recommended name: Prostaglandin E synthase (EC:5.3.99.37 Publications)Alternative name(s): Glutathione peroxidase PTGES (EC:1.11.1.-1 Publication) Glutathione transferase PTGES (EC:2.5.1.182 Publications) Microsomal glutathione S-transferase 1-like 11 Publication Short name: MGST1-L11 Publication Microsomal prostaglandin E synthase 11 Publication Short name: MPGES-11 Publication p53-induced gene 12 protein1 Publication |
Gene namesi | Name:PTGES Synonyms:MGST1L11 Publication, MPGES1, PGES, PIG121 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000148344.10 |
HGNCi | HGNC:9599, PTGES |
MIMi | 605172, gene |
neXtProti | NX_O14684 |
Subcellular locationi
Other locations
- Membrane 4 Publications; Multi-pass membrane protein 1 Publication
- perinuclear region 1 Publication
Note: Colocalizes with PTGS1/COX-1 and PTGS2/COX-2 in the perinuclear compartment.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: Reactome
Nucleus
- nuclear envelope lumen Source: Ensembl
Other locations
- integral component of membrane Source: UniProtKB
- membrane Source: ProtInc
- perinuclear region of cytoplasm Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 12 | Lumenal1 PublicationAdd BLAST | 12 | |
Transmembranei | 13 – 41 | Helical1 PublicationAdd BLAST | 29 | |
Topological domaini | 42 – 60 | Cytoplasmic1 PublicationAdd BLAST | 19 | |
Transmembranei | 61 – 90 | Helical1 PublicationAdd BLAST | 30 | |
Topological domaini | 91 – 95 | Lumenal1 Publication | 5 | |
Transmembranei | 96 – 119 | Helical1 PublicationAdd BLAST | 24 | |
Topological domaini | 120 – 123 | Cytoplasmic1 Publication | 4 | |
Transmembranei | 124 – 152 | Helical1 PublicationAdd BLAST | 29 |
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 36 | Q → E: Keeps about 40-50% of prostaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 49 | D → A: Loss of prostaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 49 | D → N: Loss of prostaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 66 | E → A: Reduces protaglandin-E synthase activity by 50%. 1 Publication | 1 | |
Mutagenesisi | 67 | R → A: Loss of prostaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 70 | R → A: Slightly reduced protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 70 | R → S: No effect on protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 72 | H → A: Reduces protaglandin-E synthase activity by 70%. 1 Publication | 1 | |
Mutagenesisi | 73 | R → A: Retains partial of protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 73 | R → L: Loss of protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 110 | R → A or S: Loss of protaglandin-E synthase activity. 2 Publications | 1 | |
Mutagenesisi | 110 | R → T: Retains 17.8% of protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 114 | T → V: Retains 21.3% activity of protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 117 | Y → A: Loss of protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 117 | Y → F: No effect on protaglandin-E synthase activity. 2 Publications | 1 | |
Mutagenesisi | 126 | R → A or L: Loss of prostaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 126 | R → K: Loss of prostaglandin-E synthase activity. Transforms prostaglandin-E synthase activity to prostaglandin-F(2alpha)synthase activity. 1 Publication | 1 | |
Mutagenesisi | 126 | R → Q: Loss of prostaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 127 | S → A: No effect on protaglandin-E synthase activity. 2 Publications | 1 | |
Mutagenesisi | 130 | Y → I: Loss of protaglandin-E synthase activity. 1 Publication | 1 | |
Mutagenesisi | 134 | Q → E: Keeps about 40-50% of prostaglandin-E synthase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9536 |
OpenTargetsi | ENSG00000148344 |
PharmGKBi | PA33948 |
Miscellaneous databases
Pharosi | O14684, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5658 |
DrugCentrali | O14684 |
GuidetoPHARMACOLOGYi | 1377 |
Polymorphism and mutation databases
BioMutai | PTGES |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000217745 | 1 – 152 | Prostaglandin E synthaseAdd BLAST | 152 |
Proteomic databases
EPDi | O14684 |
jPOSTi | O14684 |
MassIVEi | O14684 |
MaxQBi | O14684 |
PaxDbi | O14684 |
PeptideAtlasi | O14684 |
PRIDEi | O14684 |
ProteomicsDBi | 48167 |
TopDownProteomicsi | O14684 |
PTM databases
iPTMneti | O14684 |
PhosphoSitePlusi | O14684 |
SwissPalmi | O14684 |
Expressioni
Inductioni
Induced by the interleukin IL1B (PubMed:10377395, PubMed:10760517). Induced By p53/TP53 (PubMed:9305847).3 Publications
Gene expression databases
Bgeei | ENSG00000148344, Expressed in palpebral conjunctiva and 196 other tissues |
Genevisiblei | O14684, HS |
Organism-specific databases
HPAi | ENSG00000148344, Group enriched (ductus deferens, placenta, seminal vesicle) |
Interactioni
Subunit structurei
Homotrimer.
2 PublicationsBinary interactionsi
Hide detailsO14684
Protein-protein interaction databases
BioGRIDi | 114912, 21 interactors |
IntActi | O14684, 19 interactors |
STRINGi | 9606.ENSP00000342385 |
Chemistry databases
BindingDBi | O14684 |
Miscellaneous databases
RNActi | O14684, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O14684 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O14684 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 73 – 77 | Glutathione bindingCombined sources2 Publications | 5 | |
Regioni | 126 – 130 | Glutathione bindingCombined sources2 Publications | 5 |
Sequence similaritiesi
Belongs to the MAPEG family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502RZBK, Eukaryota |
GeneTreei | ENSGT00390000011980 |
HOGENOMi | CLU_105467_1_1_1 |
InParanoidi | O14684 |
OMAi | IKMYAVA |
PhylomeDBi | O14684 |
TreeFami | TF105327 |
Family and domain databases
Gene3Di | 1.20.120.550, 1 hit |
InterProi | View protein in InterPro IPR023352, MAPEG-like_dom_sf IPR001129, Membr-assoc_MAPEG IPR040162, MGST1-like |
PANTHERi | PTHR10689, PTHR10689, 1 hit |
Pfami | View protein in Pfam PF01124, MAPEG, 1 hit |
SUPFAMi | SSF161084, SSF161084, 1 hit |
i Sequence
Sequence statusi: Complete.
O14684-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPAHSLVMSS PALPAFLLCS TLLVIKMYVV AIITGQVRLR KKAFANPEDA
60 70 80 90 100
LRHGGPQYCR SDPDVERCLR AHRNDMETIY PFLFLGFVYS FLGPNPFVAW
110 120 130 140 150
MHFLVFLVGR VAHTVAYLGK LRAPIRSVTY TLAQLPCASM ALQILWEAAR
HL
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 55 | G → GG in AAC39534 (PubMed:9305847).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF010316 mRNA Translation: AAC39534.1 AF027740 mRNA Translation: AAB82299.1 AJ271802, AJ271803, AJ271804 Genomic DNA Translation: CAB72099.1 AK311947 mRNA Translation: BAG34888.1 EF543149 Genomic DNA Translation: ABQ01233.1 AL590369 Genomic DNA No translation available. AL592219 Genomic DNA No translation available. BC008280 mRNA Translation: AAH08280.1 |
CCDSi | CCDS6927.1 |
RefSeqi | NP_004869.1, NM_004878.4 |
Genome annotation databases
Ensembli | ENST00000340607; ENSP00000342385; ENSG00000148344 |
GeneIDi | 9536 |
KEGGi | hsa:9536 |
UCSCi | uc004byi.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF010316 mRNA Translation: AAC39534.1 AF027740 mRNA Translation: AAB82299.1 AJ271802, AJ271803, AJ271804 Genomic DNA Translation: CAB72099.1 AK311947 mRNA Translation: BAG34888.1 EF543149 Genomic DNA Translation: ABQ01233.1 AL590369 Genomic DNA No translation available. AL592219 Genomic DNA No translation available. BC008280 mRNA Translation: AAH08280.1 |
CCDSi | CCDS6927.1 |
RefSeqi | NP_004869.1, NM_004878.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3DWW | electron microscopy | 3.50 | A/B/C | 1-152 | [»] | |
4AL0 | X-ray | 1.16 | A | 1-152 | [»] | |
4AL1 | X-ray | 1.95 | A | 1-152 | [»] | |
4BPM | X-ray | 2.08 | A | 10-152 | [»] | |
4WAB | X-ray | 2.70 | A | 10-151 | [»] | |
4YK5 | X-ray | 1.42 | A | 2-152 | [»] | |
4YL0 | X-ray | 1.52 | A | 5-152 | [»] | |
4YL1 | X-ray | 1.41 | A | 5-152 | [»] | |
4YL3 | X-ray | 1.41 | A | 5-152 | [»] | |
5BQG | X-ray | 1.44 | A | 2-152 | [»] | |
5BQH | X-ray | 1.60 | A | 2-152 | [»] | |
5BQI | X-ray | 1.88 | A | 2-152 | [»] | |
5K0I | X-ray | 1.30 | A | 2-152 | [»] | |
5T36 | X-ray | 1.40 | A | 2-152 | [»] | |
5T37 | X-ray | 1.76 | A | 2-152 | [»] | |
5TL9 | X-ray | 1.20 | A | 2-152 | [»] | |
SMRi | O14684 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114912, 21 interactors |
IntActi | O14684, 19 interactors |
STRINGi | 9606.ENSP00000342385 |
Chemistry databases
BindingDBi | O14684 |
ChEMBLi | CHEMBL5658 |
DrugCentrali | O14684 |
GuidetoPHARMACOLOGYi | 1377 |
SwissLipidsi | SLP:000001631 |
PTM databases
iPTMneti | O14684 |
PhosphoSitePlusi | O14684 |
SwissPalmi | O14684 |
Polymorphism and mutation databases
BioMutai | PTGES |
Proteomic databases
EPDi | O14684 |
jPOSTi | O14684 |
MassIVEi | O14684 |
MaxQBi | O14684 |
PaxDbi | O14684 |
PeptideAtlasi | O14684 |
PRIDEi | O14684 |
ProteomicsDBi | 48167 |
TopDownProteomicsi | O14684 |
Protocols and materials databases
Antibodypediai | 17900, 209 antibodies |
Genome annotation databases
Ensembli | ENST00000340607; ENSP00000342385; ENSG00000148344 |
GeneIDi | 9536 |
KEGGi | hsa:9536 |
UCSCi | uc004byi.4, human |
Organism-specific databases
CTDi | 9536 |
DisGeNETi | 9536 |
EuPathDBi | HostDB:ENSG00000148344.10 |
GeneCardsi | PTGES |
HGNCi | HGNC:9599, PTGES |
HPAi | ENSG00000148344, Group enriched (ductus deferens, placenta, seminal vesicle) |
MIMi | 605172, gene |
neXtProti | NX_O14684 |
OpenTargetsi | ENSG00000148344 |
PharmGKBi | PA33948 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RZBK, Eukaryota |
GeneTreei | ENSGT00390000011980 |
HOGENOMi | CLU_105467_1_1_1 |
InParanoidi | O14684 |
OMAi | IKMYAVA |
PhylomeDBi | O14684 |
TreeFami | TF105327 |
Enzyme and pathway databases
UniPathwayi | UPA00662 |
BioCyci | MetaCyc:HS07518-MONOMER |
BRENDAi | 5.3.99.3, 2681 |
PathwayCommonsi | O14684 |
Reactomei | R-HSA-2162123, Synthesis of Prostaglandins (PG) and Thromboxanes (TX) |
SABIO-RKi | O14684 |
SIGNORi | O14684 |
Miscellaneous databases
BioGRID-ORCSi | 9536, 2 hits in 846 CRISPR screens |
ChiTaRSi | PTGES, human |
EvolutionaryTracei | O14684 |
GeneWikii | PTGES |
GenomeRNAii | 9536 |
Pharosi | O14684, Tchem |
PROi | PR:O14684 |
RNActi | O14684, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000148344, Expressed in palpebral conjunctiva and 196 other tissues |
Genevisiblei | O14684, HS |
Family and domain databases
Gene3Di | 1.20.120.550, 1 hit |
InterProi | View protein in InterPro IPR023352, MAPEG-like_dom_sf IPR001129, Membr-assoc_MAPEG IPR040162, MGST1-like |
PANTHERi | PTHR10689, PTHR10689, 1 hit |
Pfami | View protein in Pfam PF01124, MAPEG, 1 hit |
SUPFAMi | SSF161084, SSF161084, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PTGES_HUMAN | |
Accessioni | O14684Primary (citable) accession number: O14684 Secondary accession number(s): O14900, Q5SZC0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | May 30, 2000 | |
Last modified: | December 2, 2020 | |
This is version 161 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families