LMPD Database

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LMP012603

UniProt Annotations

Entry Information
Gene Nameprostaglandin-endoperoxide synthase 2
Protein EntryPGH2_RAT
UniProt IDP35355
SpeciesRat
Comments
Comment typeDescription
Catalytic ActivityArachidonate + AH(2) + 2 O(2) = prostaglandin H(2) + A + H(2)O.
CofactorName=heme b; Xref=ChEBI:CHEBI:60344; Evidence= ; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit. ;
FunctionConverts 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.
InductionBy cytokines and mitogens.
MiscellaneousConversion 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.
MiscellaneousPTGS1 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.
MiscellaneousThe 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.
PathwayLipid metabolism; prostaglandin biosynthesis.
PtmS-nitrosylation by NOS2 (iNOS) activates enzyme activity. S- nitrosylation may take place on different Cys residues in addition to Cys-526 (By similarity)
SimilarityBelongs to the prostaglandin G/H synthase family
SimilarityContains 1 EGF-like domain. {ECO:0000255|PROSITE- ProRule:PRU00076}.
Subcellular LocationMicrosome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein.
SubunitHomodimer
Tissue SpecificityExpressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus.