Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.14.99.1

Official Name

prostaglandin-endoperoxide synthase

Name from literature

cyclooxygenase

Pathway from literature

the production of prostanoids/prostaglandin synthesis

Pathway from KEGG

Lipid Metabolism; Arachidonic acid metabolism; map00590

Organisms

Human (9606)

Genome localization

9q32-q33.3[5742 ], 1q25.2-q25.3[5743 ],

Comments

This enzyme acts both as a dioxygenase and as a peroxidase.

Rate-limiting Description

"The best known function of NSAIDs action is to block the enzyme cyclooxygenase, the rate limiting enzyme in the conversion of arachidonic acid to prostaglandins." (10226539)

"The enzyme cyclooxygenase (COX) is a rate-limiting step in PG production." (10395693)

"One mechanism proposed to explain this relationship is modulation by dietary fat, of mammary tumor eicosanoid levels through action at the rate limiting enzyme in eicosanoid synthesis, cyclooxygenase (COX)." (10024686)

Regulatory Information

Upstream transcription factor

1432;5578;6667;1385;7157;6720;4790;1051;2033

Regulatory type

Detail

key enzyme;

"Cyclooxygenase (COX) is the key enzyme in the conversion of arachidonic acid to prostanoids, lipid mediators involved in several physiological and pathological processes." (18420277)

feedback;

"This review covers factors influencing COX enzyme activity, the role of their products in the development and maintenance of pain and discusses recent safety concerns of COX-2 inhibitors." (17071117)

transcriptional factor;NFkappaB(4790)

"NFkappaB transcription factor is a key regulator of COX-2 expression in TNF-alpha-induced PGE2 production" (12349897)

signal pathway;p38(1432)

"p38 MAPK and NF-kappaB signaling regulate steady-state levels of COX-2 expression, p38 MAPK additionally affects stability of COX-2 mRNA in cytokine-stimulated human airway myocytes" (12871860)

signal pathway;p38(1432)

"cyclooxygenase-2 is upregulated by p38 MAPK in tumor cells" (14557269)

transcriptional factor;p300(2033)

"p300 is the predominant coactivator that is essential for COX-2 transcriptional activation by proinflammatory mediators." (14630807)

transcriptional factor;TGF-beta(7040)

"TGF-beta superfamily is part of an autocrine/paracrine system involved in the regulation of COX-2 expression in the distal pulmonary circulation" (15220111)

signal pathway;ACE

"ACE signaling may underlie the increase in COX-2 and prostacyclin levels in patients treated with ACE inhibitors." (15569856)

signal pathway;p38(1432)

"IL-1beta-induced cPLA2 and COX-2 gene expression is modulated through the p38 MAPK pathway in both neuroglioma and neuroblastoma cells." (15950779)

signal pathway;p38(1432)

"Collectively, our results demonstrate that PGE(2) at physiologically relevant concentrations induces COX-2 expression in human NPE cells via activation of EP(2)- and EP(4) receptors and phosphorylation of p38 and p42/44 MAPKs." (16256948)

signal pathway;p38(1432)

"TGF-beta1 regulates COX-2 expression in human mesangial cells through the activation of ERK1/2, p38 MAPK, and PI3K." (16820791)

phosphorylation;PKC(5578)

"Data show that regulation of HuR via protein kinase C alpha-dependent phosphorylation emphasizes the importance of posttranslational modification for stimulus-dependent HuR shuttling." (17392515)

transcriptional factor;CREB(1385)

"PRKCD-mediated CREB activation regulates ghrelin-induced COX-2 expression and dinoprostone production in colonic epithelial cells." (17455223)

transcriptional factor;CEBPB(1051)

"data demonstrated that chronic inflammation appeared to play roles in induction of CCAAT/enhancer-binding protein beta expression in prostate epithelium which was associated with increased Cyclooxygenase-2 expression and androgen receptor downregulation" (17570496)

transcriptional factor;Sp1(6667)

"EGFR activation in malignant gliomas can transcriptionally activate COX-2 expression in a process that requires p38-MAPK and Sp1/Sp3" (17616668)

signal pathway;p38(1432)

"Data show that vitamin C suppresses proliferation of the human melanoma cell line SK-MEL2 via the down-regulation of IGF-II production and IGF-IR expression, which is followed by the activation of p38 MAPK and the inhibition of COX-2 expression." (18297687)

signal pathway;p38(1432)

"Gastrin differentially induces COX-2 and IL-8 expression at the transcriptional and posttranscriptional levels by PI3K and p38 mitogen-activated protein kinase pathways, respectively." (18395088)

key enzyme;

"Stearoyl-CoA desaturase (SCD) is a key enzyme that determines the composition and metabolic fate of ingested fatty acids, in particular the conversion of trans-vaccenic acid (TVA) to conjugated linoleic acid (CLA). " (16571147)

transcriptional factor;SREBP-1c(6720)

"In vivo, the SCD1 gene remained induced upon LXR activation in the absence of sterol regulatory element-binding protein 1c (SREBP-1c), a known transcriptional regulator of SCD1." (16943421)

phosphorylation;

P35354

phosphorylation;

P35354:from_uniprot:437_Phosphoserine

phosphorylation;

P35354:from_uniprot:446_Phosphotyrosine

transcriptional factor;TP53(7157)

"Inhibition of human brain tumor cell growth by the anti-inflammatory drug, flurbiprofen." (11687965)

transcriptional factor;TP53(7157)

"Inhibition of human brain tumor cell growth by the anti-inflammatory drug, flurbiprofen." (11687965#16189514)

transcriptional factor;TP53(7157)

"Cyclooxygenase-2 interacts with p53 and interferes with p53-dependent transcription and apoptosis." (15608668)

Gene ontology

Gene ontology

GO:0005788 (C) endoplasmic reticulum lumen [P35354 ];
GO:0006928 (P) cell motion [P35354 ];
GO:0016702 (F) oxidoreductase activity, acting on single d... [P35354, P23219 ];
GO:0005886 (C) plasma membrane [P23219 ];
GO:0020037 (F) heme binding [P35354, P23219 ];
GO:0005506 (F) iron ion binding [P35354, P23219 ];
GO:0006979 (P) response to oxidative stress [P35354, P23219 ];
GO:0005794 (C) Golgi apparatus [P23219 ];
GO:0005789 (C) endoplasmic reticulum membrane [P35354, P23219 ];
GO:0019371 (P) cyclooxygenase pathway [P35354 ];
GO:0004601 (F) peroxidase activity [P35354, P23219 ];
GO:0005634 (C) nucleus [P35354, P23219 ];
GO:0005792 (C) microsome [P35354, P23219 ];
GO:0001516 (P) prostaglandin biosynthetic process [P23219 ];
GO:0004666 (F) prostaglandin-endoperoxide synthase activity [P35354, P23219, Q6LCE7 ];
GO:0055114 (P) oxidation reduction [P35354, P23219, Q6LCE7 ];
GO:0008217 (P) regulation of blood pressure [P35354, P23219 ];
GO:0050727 (P) regulation of inflammatory response [P35354 ];

Subcellular localization

Localization

endoplasmic reticulum [P35354, P23219 ];

microsome [P35354, P23219 ];

membrane [P35354, P23219 ];

Disease relevance

Disease

Likely to play a role in inflammatory diseases such as rheumatoid arthritis [P35354 ];

Links

SwissProt

P23219; P35354; Q6LCE7

Entrez Gene

5742; 5743

HPRD

07518; 02599



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  Last Modified: 2009-03-24  
  Design by Zhao Min