1. Gene Aliases

Prostaglandin-Endoperoxide Synthase 1, PGHS-1, COX1, Cyclooxygenase-1, PTGHS, Prostaglandin-Endoperoxide Synthase 1 (Prostaglandin G/H Synthase And Cyclooxygenase), Prostaglandin G/H Synthase 1, Prostaglandin H2 Synthase 1, PGH Synthase 1, EC 1.14.99.1, EC 1.14.99, PGG/HS, PCOX1, PES-1, PGHS1, COX-1, PHS 1, COX3, PHS1

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=PTGS1]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

cellular oxidant detoxification [Any process carried out at the cellular level that reduces or removes the toxicity superoxide radicals or hydrogen peroxide. GO:0098869]

cyclooxygenase pathway [The chemical reactions and pathways by which prostaglandins are formed from arachidonic acid, and in which prostaglandin-endoperoxide synthase (cyclooxygenase) catalyzes the committed step in the conversion of arachidonic acid to the prostaglandin-endoperoxides PGG2 and PGH2. GO:0019371]

learning [Any process in an organism in which a relatively long-lasting adaptive behavioral change occurs as the result of experience. GO:0007612]

maintenance of blood-brain barrier [Maintaining the structure and function of the blood-brain barrier, thus ensuring specific regulated transport of substances (e.g. macromolecules, small molecules, ions) into the brain, and out of the brain into the blood circulation.|Homeostasis and maintenance processes are regulatory processes, therefore, regulation child terms, such as: regulation of maintenance of blood-brain barrier, should not exist for these terms.
Instead, for capturing regulation at the blood-brain barrier, consider using the part_of child term: regulation of blood-brain barrier permeability. GO:0035633]

memory [The activities involved in the mental information processing system that receives (registers), modifies, stores, and retrieves informational stimuli. The main stages involved in the formation and retrieval of memory are encoding (processing of received information by acquisition), storage (building a permanent record of received information as a result of consolidation) and retrieval (calling back the stored information and use it in a suitable way to execute a given task). GO:0007613]

negative regulation of epinephrine secretion [Any process that stops, prevents, or reduces the frequency, rate or extent of the regulated release of epinephrine. GO:0032811]

negative regulation of norepinephrine secretion [Any process that decreases the frequency, rate or extent of the regulated release of norepinephrine. GO:0010700]

positive regulation of smooth muscle contraction [Any process that activates or increases the frequency, rate or extent of smooth muscle contraction. GO:0045987]

positive regulation of vasoconstriction [Any process that activates or increases the frequency, rate or extent of vasoconstriction. GO:0045907]

prostaglandin biosynthetic process [The chemical reactions and pathways resulting in the formation of prostaglandins, any of a group of biologically active metabolites which contain a cyclopentane ring. GO:0001516]

prostaglandin metabolic process [The chemical reactions and pathways involving prostaglandins, any of a group of biologically active metabolites which contain a cyclopentane ring due to the formation of a bond between two carbons of a fatty acid. They have a wide range of biological activities. GO:0006693]

regulation of blood pressure [Any process that modulates the force with which blood travels through the circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure. GO:0008217]

regulation of cell population proliferation [Any process that modulates the frequency, rate or extent of cell proliferation. GO:0042127]

response to corticosterone [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a corticosterone stimulus. Corticosterone is a 21 carbon steroid hormone of the corticosteroid type, produced in the cortex of the adrenal glands. In many species, corticosterone is the principal glucocorticoid, involved in regulation of fuel metabolism, immune reactions, and stress responses. GO:0051412]

response to fatty acid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a fatty acid stimulus. GO:0070542]

response to organonitrogen compound [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organonitrogen stimulus. An organonitrogen compound is formally a compound containing at least one carbon-nitrogen bond. GO:0010243]

response to oxidative stress [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals. GO:0006979]

MSigDB Signatures:

WP_EICOSANOID_METABOLISM_VIA_CYCLOOXYGENASES_COX: Eicosanoid metabolism via cyclooxygenases COX [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_EICOSANOID_METABOLISM_VIA_CYCLOOXYGENASES_COX.html]

REACTOME_BIOLOGICAL_OXIDATIONS: Biological oxidations [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_BIOLOGICAL_OXIDATIONS.html]

REACTOME_FATTY_ACID_METABOLISM: Fatty acid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_FATTY_ACID_METABOLISM.html]

WP_PROSTAGLANDIN_SYNTHESIS_AND_REGULATION: Prostaglandin synthesis and regulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PROSTAGLANDIN_SYNTHESIS_AND_REGULATION.html]

BIOCARTA_ACETAMINOPHEN_PATHWAY: Mechanism of Acetaminophen Activity and Toxicity [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_ACETAMINOPHEN_PATHWAY.html]

KEGG_ARACHIDONIC_ACID_METABOLISM: Arachidonic acid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_ARACHIDONIC_ACID_METABOLISM.html]

REACTOME_ARACHIDONIC_ACID_METABOLISM: Arachidonic acid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ARACHIDONIC_ACID_METABOLISM.html]

REACTOME_SYNTHESIS_OF_PROSTAGLANDINS_PG_AND_THROMBOXANES_TX: Synthesis of Prostaglandins (PG) and Thromboxanes (TX) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SYNTHESIS_OF_PROSTAGLANDINS_PG_AND_THROMBOXANES_TX.html]

WP_EICOSANOID_SYNTHESIS: Eicosanoid synthesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_EICOSANOID_SYNTHESIS.html]

7. Gene Descriptions

NCBI Gene Summary: This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]

GeneCards Summary: PTGS1 (Prostaglandin-Endoperoxide Synthase 1) is a Protein Coding gene. Diseases associated with PTGS1 include Gastric Ulcer and Urticaria. Among its related pathways are Fatty acid metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include heme binding and dioxygenase activity. An important paralog of this gene is PTGS2.

UniProtKB/Swiss-Prot Summary: Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons [PMID: 7947975]. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells. Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products.

8. Cellular Location of Gene Product

Cytoplasmic expression at variable levels in several tissues, high expression in squamous epithelia, megakaryocytes, fallopian tube, brain and subsets of cells in tissue stroma. Mainly localized to the Golgi apparatus. In addition localized to vesicles. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000095303/subcellular]

9. Mechanistic Information

Summary

The PTGS1 gene encodes for an enzyme with dual cyclooxygenase and peroxidase activities, crucial in the biosynthesis of prostanoids from arachidonate [CS: 10]. In colon-related diseases and toxicities, the dysregulation of PTGS1 plays a significant role in modulating the inflammatory response and tissue repair processes [CS: 7]. For instance, in response to DNA damage or toxic events in the colon, such as exposure to a carcinogen azoxymethane (AOM), there is an upregulation of PTGS1, leading to increased synthesis of COX-1-derived PGE(2) [CS: 8]. This increase in PGE(2) synthesis might be a mechanism to protect intestinal stem cells and reduce crypt epithelial mitosis, crucial for maintaining intestinal integrity and facilitating repair processes [CS: 5]. However, this protective response can be maladaptive in the context of chronic inflammation or continuous exposure to carcinogens, as it inadvertently supports the proliferation of damaged or abnormal cells, contributing to the development and progression of colon cancer [CS: 6].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: intestine, skin, urinary bladder (tissue enhanced) [https://www.proteinatlas.org/ENSG00000095303/tissue]

Cell type enchanced: glandular and luminal cells, granulocytes (group enriched) [https://www.proteinatlas.org/ENSG00000095303/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: