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
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1 1454 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.  
1
  • CuratedUniProtKB
GO molecular function 
Enzyme bindingdefinition[GO:0019899]  
1
  • IPIUniProtKB
Heme bindingdefinition[GO:0020037]  
  • ISSOrtholog Curator
Lipid bindingdefinition[GO:0008289] silver  
  • IEAOrtholog Compara
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Peroxidase activitydefinition[GO:0004601]  
1
  • NASUniProtKB
Prostaglandin-endoperoxide synthase activitydefinition[GO:0004666]  
2
  • IDAUniProtKB
  • IDABHF-UCL
Protein homodimerization activitydefinition[GO:0042803] silver  
  • IEAOrtholog Compara
GO biological process 
Anagendefinition[GO:0042640] silver  
  • IEAOrtholog Compara
Angiogenesisdefinition[GO:0001525] silver  
  • IEAOrtholog Compara
Bone mineralizationdefinition[GO:0030282] silver  
  • IEAOrtholog Compara
Brown fat cell differentiationdefinition[GO:0050873] silver  
  • IEAOrtholog Compara
Cellular component movementdefinition[GO:0006928]  
1
  • TASPINC
Cellular response to ATPdefinition[GO:0071318] silver  
  • IEAOrtholog Compara
Cellular response to hypoxiadefinition[GO:0071456]  
1
  • IEPUniProtKB
Cellular response to mechanical stimulusdefinition[GO:0071260] silver  
  • IEAOrtholog Compara
Cellular response to UVdefinition[GO:0034644] silver  
  • IEAOrtholog Compara
Cyclooxygenase pathwaydefinition[GO:0019371]  
1
  • IDABHF-UCL
Decidualizationdefinition[GO:0046697] silver  
  • IEAOrtholog Compara
Embryo implantationdefinition[GO:0007566] silver  
  • IEAOrtholog Compara
Inflammatory responsedefinition[GO:0006954] silver  
  • IEAOrtholog Compara
Learningdefinition[GO:0007612] silver  
  • IEAOrtholog Compara
Maintenance of blood-brain barrierdefinition[GO:0035633] silver  
  • IEAOrtholog Compara
Memorydefinition[GO:0007613] silver  
  • IEAOrtholog Compara
Negative regulation of calcium ion transportdefinition[GO:0051926] silver  
  • IEAOrtholog Compara
Negative regulation of cell cycledefinition[GO:0045786] silver  
  • IEAOrtholog Compara
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
  • IEAOrtholog Compara
Negative regulation of smooth muscle contractiondefinition[GO:0045986] silver  
  • IEAOrtholog Compara
Negative regulation of synaptic transmission, dopaminergicdefinition[GO:0032227] silver  
  • IEAOrtholog Compara
Ovulationdefinition[GO:0030728] silver  
  • IEAOrtholog Compara
Oxidation-reduction processdefinition[GO:0055114]  
  • IEAUniProtKB KW
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Positive regulation of brown fat cell differentiationdefinition[GO:0090336]  
1
  • ISSBHF-UCL
Positive regulation of cell migration involved in sprouting angiogenesisdefinition[GO:0090050]  
1
  • ISSBHF-UCL
Positive regulation of fever generationdefinition[GO:0031622]  
  • ISSOrtholog Curator
Positive regulation of fibroblast growth factor productiondefinition[GO:0090271]  
1
  • ISSBHF-UCL
Positive regulation of NF-kappaB import into nucleusdefinition[GO:0042346] silver  
  • IEAOrtholog Compara
Positive regulation of nitric oxide biosynthetic processdefinition[GO:0045429]  
1
  • ISSBHF-UCL
Positive regulation of platelet-derived growth factor productiondefinition[GO:0090362]  
  • ISSOrtholog Curator
Positive regulation of prostaglandin biosynthetic processdefinition[GO:0031394]  
1
  • NASBHF-UCL
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661] silver  
  • IEAOrtholog Compara
Positive regulation of smooth muscle contractiondefinition[GO:0045987] silver  
  • IEAOrtholog Compara
Positive regulation of synaptic plasticitydefinition[GO:0031915] silver  
  • IEAOrtholog Compara
Positive regulation of synaptic transmission, glutamatergicdefinition[GO:0051968] silver  
  • IEAOrtholog Compara
Positive regulation of transforming growth factor beta productiondefinition[GO:0071636]  
1
  • ISSBHF-UCL
Positive regulation of vasoconstrictiondefinition[GO:0045907] silver  
  • IEAOrtholog Compara
Positive regulation vascular endothelial growth factor productiondefinition[GO:0010575]  
1
  • ISSBHF-UCL
Prostaglandin biosynthetic processdefinition[GO:0001516]  
1
  • NASBHF-UCL
  • ISSOrtholog Curator
Prostaglandin metabolic processdefinition[GO:0006693]  
1
  • TASPINC
Regulation of blood pressuredefinition[GO:0008217]  
  • ISSOrtholog Curator
Regulation of inflammatory responsedefinition[GO:0050727]  
1
  • NASUniProtKB
Response to drugdefinition[GO:0042493] silver  
  • IEAOrtholog Compara
Response to estradioldefinition[GO:0032355] silver  
  • IEAOrtholog Compara
Response to fatty aciddefinition[GO:0070542] silver  
  • IEAOrtholog Compara
Response to fructosedefinition[GO:0009750] silver  
  • IEAOrtholog Compara
Response to glucocorticoiddefinition[GO:0051384] silver  
  • IEAOrtholog Compara
Response to lipopolysaccharidedefinition[GO:0032496] silver  
  • IEAOrtholog Compara
Response to lithium iondefinition[GO:0010226] silver  
  • IEAOrtholog Compara
Response to manganese iondefinition[GO:0010042] silver  
  • IEAOrtholog Compara
Response to oxidative stressdefinition[GO:0006979] silver  
  • IEAInterPro 2 GO
Response to tumor necrosis factordefinition[GO:0034612] silver  
  • IEAOrtholog Compara
Response to vitamin Ddefinition[GO:0033280] silver  
  • IEAOrtholog Compara
Sensory perception of paindefinition[GO:0019233] silver  
  • IEAOrtholog 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.  
1
  • CuratedUniProtKB
It requires the following cofactor
Binds 1 heme B (iron-protoporphyrin IX) group per subunit (By similarity).  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
This protein is involved in the following pathway
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:
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.  
  • CuratedUniProtKB
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.  
  • CuratedUniProtKB
 

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