PTGS2 - Prostaglandin G/H synthase 2 - human protein (Function)
 
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PTGS2 »  Prostaglandin G/H synthase 2   [ EC 1.14.99.1 ]
 
Protein also known as:  Prostaglandin-endoperoxide synthase 2.
Gene name:  PTGS2
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 1484 1
GENE REF ISO

Function

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Overview 
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.  
2
  • UniProtKB
GO molecular function 
Enzyme bindingdefinition[GO:0019899]  
1
  • UniProtKB
Heme bindingdefinition[GO:0020037]  
1
  • Ortholog Curator
Lipid bindingdefinition[GO:0008289] silver  
1
  • Ortholog Compara
Metal ion bindingdefinition[GO:0046872]  
1
  • UniProtKB KW
Peroxidase activitydefinition[GO:0004601]  
1
  • UniProtKB
Prostaglandin-endoperoxide synthase activitydefinition[GO:0004666]  
2
  • UniProtKB
  • BHF-UCL
Protein homodimerization activitydefinition[GO:0042803] silver  
1
  • Ortholog Compara
GO biological process 
Angiogenesisdefinition[GO:0001525] silver  
1
  • Ortholog Compara
Bone mineralizationdefinition[GO:0030282] silver  
1
  • Ortholog Compara
Brown fat cell differentiationdefinition[GO:0050873] silver  
1
  • Ortholog Compara
Cellular component movementdefinition[GO:0006928]  
1
  • PINC
Cellular response to ATPdefinition[GO:0071318] silver  
1
  • Ortholog Compara
Cellular response to hypoxiadefinition[GO:0071456]  
1
  • UniProtKB
Cellular response to mechanical stimulusdefinition[GO:0071260] silver  
1
  • Ortholog Compara
Cellular response to UVdefinition[GO:0034644] silver  
1
  • Ortholog Compara
Cyclooxygenase pathwaydefinition[GO:0019371]  
1
  • BHF-UCL
Decidualizationdefinition[GO:0046697] silver  
1
  • Ortholog Compara
Embryo implantationdefinition[GO:0007566] silver  
1
  • Ortholog Compara
Hair cycledefinition[GO:0042633] silver  
1
  • Ortholog Compara
Inflammatory responsedefinition[GO:0006954] silver  
1
  • Ortholog Compara
Learningdefinition[GO:0007612] silver  
1
  • Ortholog Compara
Maintenance of blood-brain barrierdefinition[GO:0035633] silver  
1
  • Ortholog Compara
Memorydefinition[GO:0007613] silver  
1
  • Ortholog Compara
Negative regulation of calcium ion transportdefinition[GO:0051926] silver  
1
  • Ortholog Compara
Negative regulation of cell cycledefinition[GO:0045786] silver  
1
  • Ortholog Compara
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
1
  • Ortholog Compara
Negative regulation of smooth muscle contractiondefinition[GO:0045986] silver  
1
  • Ortholog Compara
Negative regulation of synaptic transmission, dopaminergicdefinition[GO:0032227] silver  
1
  • Ortholog Compara
Ovulationdefinition[GO:0030728] silver  
1
  • Ortholog Compara
Oxidation-reduction processdefinition[GO:0055114]  
1
  • UniProtKB KW
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
1
  • Ortholog Compara
Positive regulation of brown fat cell differentiationdefinition[GO:0090336]  
1
  • BHF-UCL
Positive regulation of cell migration involved in sprouting angiogenesisdefinition[GO:0090050]  
1
  • BHF-UCL
Positive regulation of fever generationdefinition[GO:0031622]  
1
  • Ortholog Curator
Positive regulation of fibroblast growth factor productiondefinition[GO:0090271]  
1
  • BHF-UCL
Positive regulation of NF-kappaB import into nucleusdefinition[GO:0042346] silver  
1
  • Ortholog Compara
Positive regulation of nitric oxide biosynthetic processdefinition[GO:0045429]  
1
  • BHF-UCL
Positive regulation of platelet-derived growth factor productiondefinition[GO:0090362]  
1
  • Ortholog Curator
Positive regulation of prostaglandin biosynthetic processdefinition[GO:0031394]  
1
  • BHF-UCL
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661] silver  
1
  • Ortholog Compara
Positive regulation of smooth muscle contractiondefinition[GO:0045987] silver  
1
  • Ortholog Compara
Positive regulation of synaptic plasticitydefinition[GO:0031915] silver  
1
  • Ortholog Compara
Positive regulation of synaptic transmission, glutamatergicdefinition[GO:0051968] silver  
1
  • Ortholog Compara
Positive regulation of transforming growth factor beta productiondefinition[GO:0071636]  
1
  • BHF-UCL
Positive regulation of vasoconstrictiondefinition[GO:0045907] silver  
1
  • Ortholog Compara
Positive regulation vascular endothelial growth factor productiondefinition[GO:0010575]  
1
  • BHF-UCL
Prostaglandin biosynthetic processdefinition[GO:0001516]  
2
  • BHF-UCL
  • Ortholog Curator
Prostaglandin metabolic processdefinition[GO:0006693]  
1
  • PINC
Regulation of blood pressuredefinition[GO:0008217]  
1
  • Ortholog Curator
Regulation of inflammatory responsedefinition[GO:0050727]  
1
  • UniProtKB
Response to drugdefinition[GO:0042493] silver  
1
  • Ortholog Compara
Response to estradioldefinition[GO:0032355] silver  
1
  • Ortholog Compara
Response to fatty aciddefinition[GO:0070542] silver  
1
  • Ortholog Compara
Response to fructosedefinition[GO:0009750] silver  
1
  • Ortholog Compara
Response to glucocorticoiddefinition[GO:0051384] silver  
1
  • Ortholog Compara
Response to lipopolysaccharidedefinition[GO:0032496] silver  
1
  • Ortholog Compara
Response to lithium iondefinition[GO:0010226] silver  
1
  • Ortholog Compara
Response to manganese iondefinition[GO:0010042] silver  
1
  • Ortholog Compara
Response to oxidative stressdefinition[GO:0006979] silver  
1
  • InterPro 2 GO
Response to tumor necrosis factordefinition[GO:0034612] silver  
1
  • Ortholog Compara
Response to vitamin Ddefinition[GO:0033280] silver  
1
  • Ortholog Compara
Sensory perception of paindefinition[GO:0019233] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 1.14.99.1: Arachidonate + AH(2) + 2 O(2) prostaglandin H(2) + A + H(2)O.  
2
  • UniProtKB
It requires the following cofactor
 heme b : Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.  
1
  • UniProtKB
 
More information is available from:
Pathways 
This protein is involved in the following pathway
Lipid metabolism; prostaglandin biosynthesis  
1
  • UniProtKB
According to KEGG, this protein belongs to the following pathways:
Arachidonic acid metabolism  hsa00590+5743  
Leishmaniasis  hsa05140+5743  
Metabolic pathways  hsa01100+5743  
Pathways in cancer  hsa05200+5743  
Small cell lung cancer  hsa05222+5743  
VEGF signaling pathway  hsa04370+5743  
According to Reactome, this protein belongs to the following pathways:
Nicotinamide salvaging  REACT_11213  
Synthesis of 15-eicosatetraenoic acid derivatives  REACT_150422  
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)  REACT_150149  
 
More information is available from:
Note 
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.  
1
  • UniProtKB
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.  
1
  • UniProtKB
 

Biophysicochemical properties

Kinetic parameters
KM 16.2 uM for arachidonate (in absence of sodium nitroprusside NO donor)
KM 17.0 uM for arachidonate (in presence of sodium nitroprusside NO donor)
Vmax 81.3 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor)
Vmax 132 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor)

Keywords

Biological process 
Fatty acid biosynthesis  definition   [KW-0275]
Fatty acid metabolism  definition   [KW-0276]
Lipid biosynthesis  definition   [KW-0444]
Lipid metabolism  definition   [KW-0443]
Prostaglandin biosynthesis  definition   [KW-0643]
Prostaglandin metabolism  definition   [KW-0644]
Molecular function 
Dioxygenase  definition   [KW-0223]
Oxidoreductase  definition   [KW-0560]
Peroxidase  definition   [KW-0575]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: P35354
Other
GeneWiki: PTGS2
GeneWiki: Prostaglandin-endoperoxide_synthase_2
GenomeRNAi: 5743
PRO: PR:P35354
Chemistry
GuidetoPHARMACOLOGY: 1376