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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.10
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.10
Cofactor	Glutathione. Ref.10
Subunit structure	Homotrimer.
Subcellular location	Membrane; Multi-pass membrane protein Ref.10.
Induction	By p53/TP53. Ref.1
Sequence similarities	Belongs to the MAPEG family.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid synthesis Prostaglandin biosynthesis
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	Isomerase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	prostaglandin biosynthetic process Inferred from direct assay Ref.10. Source: UniProtKB signal transduction Non-traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from direct assay Ref.10. Source: UniProtKB
Molecular function	glutathione binding Inferred from direct assay Ref.10. Source: UniProtKB prostaglandin-E synthase activity Inferred from direct assay Ref.10. 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.10
	Transmembrane	13 – 41	29	Helical
	Topological domain	42 – 60	19	Cytoplasmic Ref.10
	Transmembrane	61 – 90	30	Helical
	Topological domain	91 – 95	5	Lumenal Ref.10
	Transmembrane	96 – 119	24	Helical
	Topological domain	120 – 123	4	Cytoplasmic Ref.10
	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.10
	Mutagenesis	67	1	R → A: Loss of enzyme activity. Ref.10
	Mutagenesis	70	1	R → A: Slightly reduced enzyme activity. Ref.10
	Mutagenesis	72	1	H → A: Reduces enzyme activity by 70%. Ref.10
	Mutagenesis	110	1	R → A or S: Loss of enzyme activity. Ref.10
	Mutagenesis	117	1	Y → A: Loss of enzyme activity. Ref.10
	Mutagenesis	117	1	Y → F: No effect on enzyme activity. Ref.10
	Sequence conflict	55	1	G → GG in AAC39534. Ref.1

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: 9305847] [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: 10377395] [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: 10760517] [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: 14702039] [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: 15164053] [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: 15489334] [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: 12460774] [Abstract] Cited for: ENZYME KINETICS.
[9]	"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: 12672824] [Abstract] Cited for: STRUCTURE BY ELECTRON CRYOMICROSCOPY.
[10]	"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: 18682561] [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.
+	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	[»]

ProteinModelPortal

O14684.

SMR

O14684. Positions 11-152.

ModBase

Search...

Protein-protein interaction databases

STRING

O14684.

Proteomic databases

PeptideAtlas

O14684.

PRIDE

O14684.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340607; ENSP00000342385; ENSG00000148344.

GeneID

9536.

KEGG

hsa:9536.

UCSC

uc004byi.1. human.

Organism-specific databases

CTD

9536.

GeneCards

GC09M132500.

H-InvDB

HIX0008455.

HGNC

HGNC:9599. PTGES.

HPA

HPA045064.

MIM

605172. gene.

neXtProt

NX_O14684.

PharmGKB

PA33948.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18031.

HOGENOM

HBG715550.

HOVERGEN

HBG052470.

InParanoid

O14684.

OMA

LPCASMA.

OrthoDB

EOG4SBF09.

PhylomeDB

O14684.

Enzyme and pathway databases

BRENDA

5.3.99.3. 2681.

Gene expression databases

ArrayExpress

O14684.

CleanEx

HS_PTGES.

Genevestigator

O14684.

GermOnline

ENSG00000148344. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:1.20.120.550. G3DSA:1.20.120.550. 1 hit.

KO

K05309.

Pfam

PF01124. MAPEG. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

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:	January 25, 2012
This is version 89 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.