O14684 (PTGES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	152 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Prostaglandin biosynthesis Prostaglandin metabolism
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	Isomerase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acute inflammatory response Inferred from electronic annotation. Source: Compara chronic inflammatory response Inferred from electronic annotation. Source: Compara cyclooxygenase pathway Traceable author statement. Source: Reactome negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to calcium ion Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara response to retinoic acid Inferred from electronic annotation. Source: Compara signal transduction Non-traceable author statement Ref.2. Source: ProtInc
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from direct assay Ref.11. Source: UniProtKB nuclear envelope lumen Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	glutathione 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 152

152

Prostaglandin E synthase

PRO_0000217745

Regions

Topological domain

1 – 12

12

Lumenal Ref.11 Ref.12

Transmembrane

13 – 41

29

Helical

Topological domain

42 – 60

19

Cytoplasmic Ref.11 Ref.12

Transmembrane

61 – 90

30

Helical

Topological domain

91 – 95

5

Lumenal Ref.11 Ref.12

Transmembrane

96 – 119

24

Helical

Topological domain

120 – 123

4

Cytoplasmic Ref.11 Ref.12

Transmembrane

124 – 152

29

Helical

Region

28 – 38

11

Glutathione binding

Region

70 – 77

8

Glutathione binding

Region

110 – 113

4

Glutathione binding

Sites

Binding site

117

1

Glutathione

Binding site

126

1

Glutathione

Binding site

130

1

Glutathione

Binding site

134

1

Glutathione

Experimental info

Mutagenesis

66

1

E → A: Reduces enzyme activity by 50%. Ref.11

Mutagenesis

67

1

R → A: Loss of enzyme activity. Ref.11

Mutagenesis

70

1

R → A: Slightly reduced enzyme activity. Ref.11

Mutagenesis

72

1

H → A: Reduces enzyme activity by 70%. Ref.11

Mutagenesis

110

1

R → A or S: Loss of enzyme activity. Ref.11

Mutagenesis

117

1

Y → A: Loss of enzyme activity. Ref.11

Mutagenesis

117

1

Y → F: No effect on enzyme activity. Ref.11

Sequence conflict

55

1

G → GG in AAC39534. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

152

Helix Strand Turn

Details...

Helix

13 – 41

29

Beta strand

44 – 46

3

Helix

47 – 52

6

Helix

56 – 58

3

Helix

63 – 90

28

Helix

96 – 118

23

Helix

125 – 150

26

Sequences

	Sequence		Length	Mass (Da)
	O14684 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: BF9B9ED81CA67A3D	FASTA	152	17,102
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00297858.

RefSeq

NP_004869.1. NM_004878.4.

UniGene

Hs.146688.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

O14684.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000342385.

Proteomic databases

PaxDb

O14684.

PeptideAtlas

O14684.

PRIDE

O14684.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340607; ENSP00000342385; ENSG00000148344.

GeneID

9536.

KEGG

hsa:9536.

UCSC

uc004byi.3. human.

Organism-specific databases

CTD

9536.

GeneCards

GC09M132500.

HGNC

HGNC:9599. PTGES.

HPA

HPA045064.

MIM

605172. gene.

neXtProt

NX_O14684.

PharmGKB

PA33948.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG67817.

HOGENOM

HOG000231759.

HOVERGEN

HBG052470.

InParanoid

O14684.

KO

K15729.

OMA

LLVIKMY.

OrthoDB

EOG4SBF09.

PhylomeDB

O14684.

Enzyme and pathway databases

BioCyc

MetaCyc:HS07518-MONOMER.

BRENDA

5.3.99.3. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

O14684.

CleanEx

HS_PTGES.

Genevestigator

O14684.

GermOnline

ENSG00000148344. Homo sapiens.

Family and domain databases

Gene3D

1.20.120.550. 1 hit.

InterPro

IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]

Pfam

PF01124. MAPEG. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O14684.

ChEMBL

CHEMBL5658.

ChiTaRS

PTGES. human.

EvolutionaryTrace

O14684.

GenomeRNAi

9536.

NextBio

35754.

SOURCE

Search...

Entry information

Entry name

PTGES_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.