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O14684 (PTGES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prostaglandin E synthase

EC=5.3.99.3
Alternative name(s):
Microsomal glutathione S-transferase 1-like 1
Short name=MGST1-L1
Microsomal prostaglandin E synthase 1
Short name=MPGES-1
p53-induced gene 12 protein
Gene names
Name:PTGES
Synonyms:MGST1L1, MPGES1, PGES, PIG12
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length152 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Ref.11

Catalytic activity

(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. Ref.11

Cofactor

Glutathione. Ref.11

Subunit structure

Homotrimer. Ref.12

Subcellular location

Membrane; Multi-pass membrane protein Ref.11.

Induction

By p53/TP53. Ref.1

Sequence similarities

Belongs to the MAPEG family.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Prostaglandin biosynthesis
Prostaglandin metabolism
   Cellular componentMembrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionIsomerase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacute inflammatory response

Inferred from electronic annotation. Source: Ensembl

arachidonic acid metabolic process

Traceable author statement. Source: Reactome

chronic inflammatory response

Inferred from electronic annotation. Source: Ensembl

cyclooxygenase pathway

Traceable author statement. Source: Reactome

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

prostaglandin biosynthetic process

Inferred from direct assay Ref.11. Source: UniProtKB

prostaglandin metabolic process

Traceable author statement Ref.2. Source: ProtInc

response to calcium ion

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.2. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from direct assay Ref.11. Source: UniProtKB

membrane

Traceable author statement Ref.2. Source: ProtInc

nuclear envelope lumen

Inferred from electronic annotation. Source: Ensembl

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionglutathione binding

Inferred from direct assay Ref.11. Source: UniProtKB

prostaglandin-E synthase activity

Inferred from direct assay Ref.11. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 152152Prostaglandin E synthase
PRO_0000217745

Regions

Topological domain1 – 1212Lumenal Ref.11 Ref.12
Transmembrane13 – 4129Helical
Topological domain42 – 6019Cytoplasmic Ref.11 Ref.12
Transmembrane61 – 9030Helical
Topological domain91 – 955Lumenal Ref.11 Ref.12
Transmembrane96 – 11924Helical
Topological domain120 – 1234Cytoplasmic Ref.11 Ref.12
Transmembrane124 – 15229Helical
Region28 – 3811Glutathione binding
Region70 – 778Glutathione binding
Region110 – 1134Glutathione binding

Sites

Binding site1171Glutathione
Binding site1261Glutathione
Binding site1301Glutathione
Binding site1341Glutathione

Experimental info

Mutagenesis661E → A: Reduces enzyme activity by 50%. Ref.11
Mutagenesis671R → A: Loss of enzyme activity. Ref.11
Mutagenesis701R → A: Slightly reduced enzyme activity. Ref.11
Mutagenesis721H → A: Reduces enzyme activity by 70%. Ref.11
Mutagenesis1101R → A or S: Loss of enzyme activity. Ref.11
Mutagenesis1171Y → A: Loss of enzyme activity. Ref.11
Mutagenesis1171Y → F: No effect on enzyme activity. Ref.11
Sequence conflict551G → GG in AAC39534. Ref.1

Secondary structure

.............. 152
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O14684 [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: BF9B9ED81CA67A3D

FASTA15217,102
        10         20         30         40         50         60 
MPAHSLVMSS PALPAFLLCS TLLVIKMYVV AIITGQVRLR KKAFANPEDA LRHGGPQYCR 

        70         80         90        100        110        120 
SDPDVERCLR AHRNDMETIY PFLFLGFVYS FLGPNPFVAW MHFLVFLVGR VAHTVAYLGK 

       130        140        150 
LRAPIRSVTY TLAQLPCASM ALQILWEAAR HL 

« Hide

References

« Hide 'large scale' references
[1]"A model for p53-induced apoptosis."
Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B.
Nature 389:300-306(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION BY TP53.
Tissue: Colon cancer.
[2]"Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target."
Jakobsson P.-J., Thoren S., Morgenstern R., Samuelsson B.
Proc. Natl. Acad. Sci. U.S.A. 96:7220-7225(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Human glutathione dependent prostaglandin E synthase: gene structure and regulation."
Forsberg L., Leeb L., Thoren S., Morgenstern R., Jakobsson P.J.
FEBS Lett. 471:78-82(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary gland.
[5]SeattleSNPs variation discovery resource
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[8]"Purification and characterization of recombinant microsomal prostaglandin E synthase-1."
Ouellet M., Falgueyret J.-P., Ear P.H., Pen A., Mancini J.A., Riendeau D., Percival M.D.
Protein Expr. Purif. 26:489-495(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME KINETICS.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination."
Thoren S., Weinander R., Saha S., Jegerschold C., Pettersson P.L., Samuelsson B., Hebert H., Hamberg M., Morgenstern R., Jakobsson P.-J.
J. Biol. Chem. 278:22199-22209(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY ELECTRON CRYOMICROSCOPY.
[11]"Structural basis for induced formation of the inflammatory mediator prostaglandin E2."
Jegerschold C., Pawelzik S.C., Purhonen P., Bhakat P., Gheorghe K.R., Gyobu N., Mitsuoka K., Morgenstern R., Jakobsson P.J., Hebert H.
Proc. Natl. Acad. Sci. U.S.A. 105:11110-11115(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.5 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, TRANSMEMBRANE TOPOLOGY, MUTAGENESIS OF GLU-66; ARG-67; ARG-70; HIS-72; ARG-110 AND TYR-117.
[12]"Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily."
Sjogren T., Nord J., Ek M., Johansson P., Liu G., Geschwindner S.
Proc. Natl. Acad. Sci. U.S.A. 110:3806-3811(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.16 ANGSTROMS) IN COMPLEXES WITH GLUTATIONE, SUBUNIT, PROBABLE TOPOLOGY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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, AL592219 Genomic DNA. Translation: CAI14506.1.
AL592219, AL590369 Genomic DNA. Translation: CAI16116.1.
BC008280 mRNA. Translation: AAH08280.1.
RefSeqNP_004869.1. NM_004878.4.
UniGeneHs.146688.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3DWWelectron microscopy3.50A/B/C1-152[»]
4AL0X-ray1.16A1-152[»]
4AL1X-ray1.95A1-152[»]
ProteinModelPortalO14684.
SMRO14684. Positions 7-152.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114912. 2 interactions.
STRING9606.ENSP00000342385.

Chemistry

BindingDBO14684.
ChEMBLCHEMBL5658.

Proteomic databases

PaxDbO14684.
PeptideAtlasO14684.
PRIDEO14684.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340607; ENSP00000342385; ENSG00000148344.
GeneID9536.
KEGGhsa:9536.
UCSCuc004byi.3. human.

Organism-specific databases

CTD9536.
GeneCardsGC09M132500.
HGNCHGNC:9599. PTGES.
HPAHPA045064.
MIM605172. gene.
neXtProtNX_O14684.
PharmGKBPA33948.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG67817.
HOGENOMHOG000231759.
HOVERGENHBG052470.
InParanoidO14684.
KOK15729.
OMALLVIKMY.
OrthoDBEOG7288T0.
PhylomeDBO14684.
TreeFamTF105327.

Enzyme and pathway databases

BioCycMetaCyc:HS07518-MONOMER.
BRENDA5.3.99.3. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

BgeeO14684.
CleanExHS_PTGES.
GenevestigatorO14684.

Family and domain databases

Gene3D1.20.120.550. 1 hit.
InterProIPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]
PfamPF01124. MAPEG. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPTGES. human.
EvolutionaryTraceO14684.
GeneWikiPTGES.
GenomeRNAi9536.
NextBio35754.
PROO14684.
SOURCESearch...

Entry information

Entry namePTGES_HUMAN
AccessionPrimary (citable) accession number: O14684
Secondary accession number(s): O14900, Q5SZC0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: April 16, 2014
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM