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Protein

Prostaglandin G/H synthase 2

Gene

Ptgs2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.5 Publications

Miscellaneous

The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site.
Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PGHS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PGHS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.
PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.

Catalytic activityi

Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.4 Publications

Cofactori

heme b3 PublicationsNote: Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.3 Publications

Activity regulationi

Inhibited by the nonsteroidal anti-inflammatory drugs aspirin, naproxen, diclofenac, meclofenamic acid, indomethacin and their analogs.2 Publications

Pathwayi: prostaglandin biosynthesis

This protein is involved in the pathway prostaglandin biosynthesis, which is part of Lipid metabolism.4 Publications
View all proteins of this organism that are known to be involved in the pathway prostaglandin biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei106SubstrateCombined sources1 Publication1
Active sitei193Proton acceptorPROSITE-ProRule annotation1 Publication1
Binding sitei341SubstrateCombined sources1 Publication1
Active sitei371For cyclooxygenase activity1 Publication1
Metal bindingi374Iron (heme axial ligand)Combined sources5 Publications1
Sitei516Aspirin-acetylated serine1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase, Peroxidase
Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.99.1 3474
ReactomeiR-MMU-197264 Nicotinamide salvaging
R-MMU-2142770 Synthesis of 15-eicosatetraenoic acid derivatives
R-MMU-2162123 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
R-MMU-9018677 Biosynthesis of DHA-derived SPMs
R-MMU-9018679 Biosynthesis of EPA-derived SPMs
R-MMU-9025094 Biosynthesis of DPAn-3 SPMs
R-MMU-9027604 Biosynthesis of electrophilic Omega-3 PUFA oxo-derivatives
UniPathwayi
UPA00662

Protein family/group databases

PeroxiBasei3360 MmPGHS02

Chemistry databases

SwissLipidsiSLP:000001129

Names & Taxonomyi

Protein namesi
Recommended name:
Prostaglandin G/H synthase 2 (EC:1.14.99.1)
Alternative name(s):
Cyclooxygenase-2
Short name:
COX-2
Glucocorticoid-regulated inflammatory cyclooxygenase
Gripghs
Macrophage activation-associated marker protein P71/73
PES-2
PHS II
Prostaglandin H2 synthase 2
Short name:
PGH synthase 2
Short name:
PGHS-2
Prostaglandin-endoperoxide synthase 2
TIS10 protein
Gene namesi
Name:Ptgs2
Synonyms:Cox-2, Cox2, Pghs-b, Tis10
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:97798 Ptgs2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Disruption phenotypei

Mutant mice exhibit defects in colonic mucosal wound repair.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi517L → A, F, P or T: Slightly reduced activity. 1 Publication1
Mutagenesisi580N → A: Loss of glycosylation site. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4321

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Add BLAST17
ChainiPRO_000002387618 – 604Prostaglandin G/H synthase 2Add BLAST587

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 32Combined sources7 Publications
Disulfide bondi22 ↔ 145Combined sources7 Publications
Disulfide bondi26 ↔ 42Combined sources7 Publications
Disulfide bondi44 ↔ 54Combined sources7 Publications
GlycosylationiCAR_00022253N-linked (GlcNAc...) asparagineCombined sources8 Publications1
GlycosylationiCAR_000223130N-linked (GlcNAc...) asparagineCombined sources8 Publications1
GlycosylationiCAR_000224396N-linked (GlcNAc...) asparagineCombined sources8 Publications1
Disulfide bondi555 ↔ 561Combined sources7 Publications
GlycosylationiCAR_000225580N-linked (GlcNAc...) asparagine2 Publications1

Post-translational modificationi

S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei592Not glycosylated1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, S-nitrosylation

Proteomic databases

PaxDbiQ05769
PeptideAtlasiQ05769
PRIDEiQ05769

PTM databases

GlyConnecti514
iPTMnetiQ05769
PhosphoSitePlusiQ05769
SwissPalmiQ05769
UniCarbKBiQ05769

Expressioni

Tissue specificityi

Following colon injury, expressed in the wound bed mesenchyme during the first phase of repair, probably by colonic mesenchymal stem cells (at protein level).1 Publication

Developmental stagei

During colonic wound repair, highly up-regulated (more than 1600-fold) in the mesenchyme of the wound bed 2 days after injury as compared to uninjured mucosa. Further increase in expression is observed at day 4 following injury (close to 2200-fold). Down-regulated at day 6 (only 93-fold increase as compared to uninjured mucosa).1 Publication

Inductioni

By cytokines and mitogens.

Gene expression databases

BgeeiENSMUSG00000032487 Expressed in 136 organ(s), highest expression level in cumulus cell
CleanExiMM_PTGS2
ExpressionAtlasiQ05769 baseline and differential
GenevisibleiQ05769 MM

Interactioni

Subunit structurei

Homodimer.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Nos1Q9Z0J44EBI-298933,EBI-397596

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202463, 6 interactors
DIPiDIP-31082N
IntActiQ05769, 2 interactors
STRINGi10090.ENSMUSP00000035065

Chemistry databases

BindingDBiQ05769

Structurei

Secondary structure

1604
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ05769
SMRiQ05769
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ05769

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 55EGF-likePROSITE-ProRule annotationAdd BLAST38

Sequence similaritiesi

Belongs to the prostaglandin G/H synthase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2408 Eukaryota
ENOG410XPZ3 LUCA
GeneTreeiENSGT00390000010743
HOGENOMiHOG000013149
HOVERGENiHBG000366
InParanoidiQ05769
KOiK11987
OMAiCNNVKGC
OrthoDBiEOG091G03CD
PhylomeDBiQ05769
TreeFamiTF329675

Family and domain databases

Gene3Di1.10.640.10, 1 hit
InterProiView protein in InterPro
IPR029576 COX-2
IPR000742 EGF-like_dom
IPR010255 Haem_peroxidase
IPR019791 Haem_peroxidase_animal
IPR037120 Haem_peroxidase_sf
PANTHERiPTHR11903:SF8 PTHR11903:SF8, 1 hit
PfamiView protein in Pfam
PF03098 An_peroxidase, 1 hit
PF00008 EGF, 1 hit
PRINTSiPR00457 ANPEROXIDASE
SUPFAMiSSF48113 SSF48113, 1 hit
PROSITEiView protein in PROSITE
PS50026 EGF_3, 1 hit
PS50292 PEROXIDASE_3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q05769-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLFRAVLLCA ALGLSQAANP CCSNPCQNRG ECMSTGFDQY KCDCTRTGFY
60 70 80 90 100
GENCTTPEFL TRIKLLLKPT PNTVHYILTH FKGVWNIVNN IPFLRSLIMK
110 120 130 140 150
YVLTSRSYLI DSPPTYNVHY GYKSWEAFSN LSYYTRALPP VADDCPTPMG
160 170 180 190 200
VKGNKELPDS KEVLEKVLLR REFIPDPQGS NMMFAFFAQH FTHQFFKTDH
210 220 230 240 250
KRGPGFTRGL GHGVDLNHIY GETLDRQHKL RLFKDGKLKY QVIGGEVYPP
260 270 280 290 300
TVKDTQVEMI YPPHIPENLQ FAVGQEVFGL VPGLMMYATI WLREHNRVCD
310 320 330 340 350
ILKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE
360 370 380 390 400
LLFNQQFQYQ NRIASEFNTL YHWHPLLPDT FNIEDQEYSF KQFLYNNSIL
410 420 430 440 450
LEHGLTQFVE SFTRQIAGRV AGGRNVPIAV QAVAKASIDQ SREMKYQSLN
460 470 480 490 500
EYRKRFSLKP YTSFEELTGE KEMAAELKAL YSDIDVMELY PALLVEKPRP
510 520 530 540 550
DAIFGETMVE LGAPFSLKGL MGNPICSPQY WKPSTFGGEV GFKIINTASI
560 570 580 590 600
QSLICNNVKG CPFTSFNVQD PQPTKTATIN ASASHSRLDD INPTVLIKRR

STEL
Length:604
Mass (Da):69,013
Last modified:June 1, 1994 - v1
Checksum:iDFE1658295C92064
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WPT2A0A087WPT2_MOUSE
Prostaglandin G/H synthase 2
Ptgs2
62Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti98I → T in AAA39924 (PubMed:1712772).Curated1
Sequence conflicti142A → R in AAA39918 (PubMed:1419907).Curated1
Sequence conflicti301I → L no nucleotide entry (PubMed:1744122).Curated1
Sequence conflicti585H → R in AAA39918 (PubMed:1419907).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64291 mRNA Translation: AAA39924.1
M94967 mRNA Translation: AAA39918.1
M82866
, M82862, M82863, M82864, M82865 Genomic DNA Translation: AAA40448.1
M88242 mRNA Translation: AAA37740.1
AK049923 mRNA Translation: BAC33986.1
AK144956 mRNA Translation: BAE26154.1
AK166221 mRNA Translation: BAE38639.1
AK172161 mRNA Translation: BAE42855.1
CH466520 Genomic DNA Translation: EDL39487.1
CCDSiCCDS15353.1
PIRiA49010
RefSeqiNP_035328.2, NM_011198.4
UniGeneiMm.292547

Genome annotation databases

EnsembliENSMUST00000035065; ENSMUSP00000035065; ENSMUSG00000032487
GeneIDi19225
KEGGimmu:19225
UCSCiuc007cxv.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64291 mRNA Translation: AAA39924.1
M94967 mRNA Translation: AAA39918.1
M82866
, M82862, M82863, M82864, M82865 Genomic DNA Translation: AAA40448.1
M88242 mRNA Translation: AAA37740.1
AK049923 mRNA Translation: BAC33986.1
AK144956 mRNA Translation: BAE26154.1
AK166221 mRNA Translation: BAE38639.1
AK172161 mRNA Translation: BAE42855.1
CH466520 Genomic DNA Translation: EDL39487.1
CCDSiCCDS15353.1
PIRiA49010
RefSeqiNP_035328.2, NM_011198.4
UniGeneiMm.292547

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CVUX-ray2.40A/B18-569[»]
1CX2X-ray3.00A/B/C/D18-604[»]
1DCXmodel-A/B18-569[»]
1DD0model-A/B18-569[»]
1DDXX-ray3.00A/B/C/D18-569[»]
1PXXX-ray2.90A/B/C/D1-604[»]
3HS5X-ray2.10A/B20-604[»]
3HS6X-ray2.40A/B20-604[»]
3HS7X-ray2.65A/B20-604[»]
3KRKX-ray2.40A/B20-604[»]
3LN0X-ray2.20A/B/C/D18-604[»]
3LN1X-ray2.40A/B/C/D18-604[»]
3MDLX-ray2.20A/B20-599[»]
3MQEX-ray2.80A/B/C/D18-604[»]
3NT1X-ray1.73A/B18-604[»]
3NTBX-ray2.27A/B/C/D18-604[»]
3NTGX-ray2.19A/B/C/D18-569[»]
3OLTX-ray2.45A/B20-604[»]
3OLUX-ray2.35A/B20-604[»]
3PGHX-ray2.50A/B/C/D18-604[»]
3Q7DX-ray2.40A/B18-604[»]
3QH0X-ray2.10A/B1-604[»]
3QMOX-ray3.00A/B1-604[»]
3RR3X-ray2.84A/B/C/D18-577[»]
3TZIX-ray2.15A/B20-604[»]
4COXX-ray2.90A/B/C/D18-604[»]
4E1GX-ray2.10A/B1-604[»]
4FM5X-ray2.81A/B/C/D1-604[»]
4M10X-ray2.01A/B/C/D18-604[»]
4M11X-ray2.45A/B/C/D18-569[»]
4OTJX-ray2.11A/B/C/D18-604[»]
4OTYX-ray2.35A/B18-604[»]
4PH9X-ray1.81A/B20-568[»]
4RRWX-ray2.57A/B/C/D18-604[»]
4RRXX-ray2.78A/B18-604[»]
4RRYX-ray2.43A/B/C/D18-604[»]
4RRZX-ray2.57A/B/C/D18-604[»]
4RS0X-ray2.81A18-604[»]
4RUTX-ray2.16A/B/C/D18-604[»]
4Z0LX-ray2.29A/B/C/D18-604[»]
5COXX-ray3.00A/B/C/D18-604[»]
5FDQX-ray1.90A/B20-604[»]
5JVYX-ray2.36A/B20-568[»]
5JVZX-ray2.62A/B20-569[»]
5JW1X-ray2.82A/B20-569[»]
5W58X-ray2.27A18-604[»]
6COXX-ray2.80A/B18-604[»]
ProteinModelPortaliQ05769
SMRiQ05769
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202463, 6 interactors
DIPiDIP-31082N
IntActiQ05769, 2 interactors
STRINGi10090.ENSMUSP00000035065

Chemistry databases

BindingDBiQ05769
ChEMBLiCHEMBL4321
SwissLipidsiSLP:000001129

Protein family/group databases

PeroxiBasei3360 MmPGHS02

PTM databases

GlyConnecti514
iPTMnetiQ05769
PhosphoSitePlusiQ05769
SwissPalmiQ05769
UniCarbKBiQ05769

Proteomic databases

PaxDbiQ05769
PeptideAtlasiQ05769
PRIDEiQ05769

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035065; ENSMUSP00000035065; ENSMUSG00000032487
GeneIDi19225
KEGGimmu:19225
UCSCiuc007cxv.1 mouse

Organism-specific databases

CTDi5743
MGIiMGI:97798 Ptgs2

Phylogenomic databases

eggNOGiKOG2408 Eukaryota
ENOG410XPZ3 LUCA
GeneTreeiENSGT00390000010743
HOGENOMiHOG000013149
HOVERGENiHBG000366
InParanoidiQ05769
KOiK11987
OMAiCNNVKGC
OrthoDBiEOG091G03CD
PhylomeDBiQ05769
TreeFamiTF329675

Enzyme and pathway databases

UniPathwayi
UPA00662

BRENDAi1.14.99.1 3474
ReactomeiR-MMU-197264 Nicotinamide salvaging
R-MMU-2142770 Synthesis of 15-eicosatetraenoic acid derivatives
R-MMU-2162123 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
R-MMU-9018677 Biosynthesis of DHA-derived SPMs
R-MMU-9018679 Biosynthesis of EPA-derived SPMs
R-MMU-9025094 Biosynthesis of DPAn-3 SPMs
R-MMU-9027604 Biosynthesis of electrophilic Omega-3 PUFA oxo-derivatives

Miscellaneous databases

EvolutionaryTraceiQ05769
PROiPR:Q05769
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032487 Expressed in 136 organ(s), highest expression level in cumulus cell
CleanExiMM_PTGS2
ExpressionAtlasiQ05769 baseline and differential
GenevisibleiQ05769 MM

Family and domain databases

Gene3Di1.10.640.10, 1 hit
InterProiView protein in InterPro
IPR029576 COX-2
IPR000742 EGF-like_dom
IPR010255 Haem_peroxidase
IPR019791 Haem_peroxidase_animal
IPR037120 Haem_peroxidase_sf
PANTHERiPTHR11903:SF8 PTHR11903:SF8, 1 hit
PfamiView protein in Pfam
PF03098 An_peroxidase, 1 hit
PF00008 EGF, 1 hit
PRINTSiPR00457 ANPEROXIDASE
SUPFAMiSSF48113 SSF48113, 1 hit
PROSITEiView protein in PROSITE
PS50026 EGF_3, 1 hit
PS50292 PEROXIDASE_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPGH2_MOUSE
AccessioniPrimary (citable) accession number: Q05769
Secondary accession number(s): Q543K3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: September 12, 2018
This is version 194 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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