Details for: PTGS1

Gene ID: 5742

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PTGS1

Ensembl ID: ENSG00000095303

Description: prostaglandin-endoperoxide synthase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • intestinal tuft cell CL0019032
    CSI 24.91
    rCSI 38.07%
    PRS 94.46
  • tuft cell of colon CL0009041
    CSI 18.5
    rCSI 43.09%
    PRS 94.42
  • brush cell CL0002204
    CSI 17.07
    rCSI 33.79%
    PRS 95.11
  • myeloid leukocyte CL0000766
    CSI 13.83
    rCSI 12.76%
    PRS 94.5
  • promyelocyte CL0000836
    CSI 12.19
    rCSI 17.58%
    PRS 94.99
  • megakaryocyte CL0000556
    CSI 7.69
    rCSI 33.36%
    PRS 93.69
  • glutamatergic neuron CL0000679
    CSI 7.54
    rCSI 15.5%
    PRS 83.62
  • fallopian tube secretory epithelial cell CL4030006
    CSI 6.99
    rCSI 6.73%
    PRS 92.28
  • hematopoietic stem cell CL0000037
    CSI 6.47
    rCSI 4.3%
    PRS 94.41
  • platelet CL0000233
    CSI 5
    rCSI 20.76%
    PRS 89.86
  • keratinocyte CL0000312
    CSI 4.91
    rCSI 4.12%
    PRS 93.09
  • myofibroblast cell CL0000186
    CSI 3.83
    rCSI 5.31%
    PRS 90.85
  • epithelial cell CL0000066
    CSI 3.8
    rCSI 5.83%
    PRS 82.77
  • mast cell CL0000097
    CSI 3.79
    rCSI 8.19%
    PRS 91.17
  • Langerhans cell CL0000453
    CSI 3.68
    rCSI 5.62%
    PRS 97.56
  • lung macrophage CL1001603
    CSI 3.11
    rCSI 6.95%
    PRS 96.76
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.91
    rCSI 2.24%
    PRS 95.85
  • mononuclear phagocyte CL0000113
    CSI 2.69
    rCSI 5.93%
    PRS 95.56
  • granulocyte CL0000094
    CSI 2.6
    rCSI 3.98%
    PRS 96.34
  • erythrocyte CL0000232
    CSI 2.52
    rCSI 5.72%
    PRS 91.37
  • kidney collecting duct principal cell CL1001431
    CSI 2.4
    rCSI 12.07%
    PRS 89.71
  • basophil CL0000767
    CSI 2.29
    rCSI 4.85%
    PRS 96.67
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.18
    rCSI 2.63%
    PRS 96.77
  • smooth muscle cell CL0000192
    CSI 2.08
    rCSI 4.95%
    PRS 88.4
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.85
    rCSI 1.67%
    PRS 92.52
  • intermediate monocyte CL0002393
    CSI 1.79
    rCSI 2.69%
    PRS 96.46
  • pancreatic stellate cell CL0002410
    CSI 0.71
    rCSI 4.12%
    PRS 94.55
  • megakaryocyte progenitor cell CL0000553
    CSI 0.44
    rCSI 8.07%
    PRS 98.4

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PTGS1](/details-gene/5742), or Prostaglandin-Endoperoxide Synthase 1, encodes a key enzyme, also known as cyclooxygenase-1 (COX-1), that catalyzes the first committed step in the biosynthesis of prostanoids, including prostaglandins and thromboxanes. These lipid signaling molecules are crucial mediators of a wide range of physiological and pathological processes. Functionally, [PTGS1](/details-gene/5742) is involved in the [cyclooxygenase pathway](/details-cell/GO:0019371) and plays a central role in hemostasis and cytoprotection. Expression analysis indicates that **Overall**, [PTGS1](/details-gene/5742) is a defining marker for specialized chemosensory epithelial cells, such as the [intestinal tuft cell](/details-cell/CL0019032), and is also highly significant in the hematopoietic system, particularly in the myeloid lineage including [myeloid leukocyte](/details-cell/CL0000766), [promyelocyte](/details-cell/CL0000836), and [megakaryocyte](/details-cell/CL0000556), consistent with its well-established role in [platelet](/details-cell/CL0000233) function. ## Cellular Roles and Expression Landscape The expression profile of [PTGS1](/details-gene/5742) highlights its importance in distinct cellular contexts. **Overall**, the gene shows exceptionally high significance in specialized epithelial cells of the "brush/tuft" cell lineage, including [intestinal tuft cell](/details-cell/CL0019032) (CSI: 24.91), [tuft cell of colon](/details-cell/CL0009041) (CSI: 18.50), and [brush cell](/details-cell/CL0002204) (CSI: 17.07). These cells are known chemosensory sentinels in mucosal tissues, suggesting a role for [PTGS1](/details-gene/5742)-derived prostaglandins in initiating local immune or physiological responses to luminal stimuli. In parallel, [PTGS1](/details-gene/5742) is a prominent gene within the hematopoietic system. It is highly significant in [myeloid leukocyte](/details-cell/CL0000766) (CSI: 13.83) and their precursors, such as [promyelocyte](/details-cell/CL0000836) (CSI: 12.19) and [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 6.47). This pattern culminates in its critical function in [megakaryocyte](/details-cell/CL0000556) (CSI: 7.69) and their anucleated progeny, [platelet](/details-cell/CL0000233) (CSI: 5.00), where it is responsible for synthesizing thromboxane A2, a potent mediator of platelet aggregation and vasoconstriction. Broader, but still notable, expression is observed in other cell types, including [glutamatergic neuron](/details-cell/CL0000679) (CSI: 7.54), [keratinocyte](/details-cell/CL0000312) (CSI: 4.91), and general [epithelial cell](/details-cell/CL0000066) (CSI: 3.80), underscoring its role in housekeeping functions across various tissues. ## Pathways and Molecular Function Functionally, [PTGS1](/details-gene/5742) is centrally involved in lipid metabolism and signaling. Its primary molecular function is [prostaglandin-endoperoxide synthase activity](/details-cell/GO:0004666), which includes both a cyclooxygenase and a [peroxidase activity](/details-cell/GO:0004601). This dual enzymatic action converts arachidonic acid into prostaglandin H2, the precursor for all other prostanoids. This is captured by its annotation in the Reactome pathway [Synthesis of prostaglandins (pg) and thromboxanes (tx)](https://reactome.org/content/detail/R-HSA-2162123) and the broader [Arachidonate metabolism](https://reactome.org/content/detail/R-HSA-2142753) pathway. The biological processes mediated by [PTGS1](/details-gene/5742) are diverse, reflecting the widespread actions of its products. Key annotated processes include the [prostaglandin biosynthetic process](/details-cell/GO:0001516), [regulation of blood pressure](/details-cell/GO:0008217), and cellular homeostasis functions like [cellular oxidant detoxification](/details-cell/GO:0098869). Consistent with its enzymatic nature, it requires [heme binding](/details-cell/GO:0020037) for its catalytic activity. Its primary site of action is within the cell, specifically localized to the [endoplasmic reticulum membrane](/details-cell/GO:0005789). ## Research Directions The established role of [PTGS1](/details-gene/5742) as the target for non-steroidal anti-inflammatory drugs (NSAIDs) is well-documented ([Link](https://doi.org/10.4292/wjgpt.v5.i1.40)). However, the high-resolution expression data suggests new avenues for investigation, particularly concerning its role in specialized cell types. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [intestinal tuft cell](/details-cell/CL0019032), [PTGS1](/details-gene/5742) may function as a critical downstream effector of chemosensory pathways in these cells. Prostaglandins produced by [PTGS1](/details-gene/5742) could act as paracrine signals to orchestrate local type 2 immune responses, such as goblet cell hyperplasia and eosinophil recruitment, in response to allergens or parasitic infections. 2. The high significance of [PTGS1](/details-gene/5742) in myeloid progenitors like the [promyelocyte](/details-cell/CL0000836) suggests that prostanoid signaling may play a role in regulating myeloid lineage commitment or the functional programming of mature myeloid cells, beyond its classic role in inflammation. **Key Experimental Proposal:** To test the first hypothesis regarding the role of [PTGS1](/details-gene/5742) in tuft cell function, a key experiment would be to generate a conditional knockout mouse model. Using a *Dclk1-CreER* driver to specifically delete *Ptgs1* in tuft cells upon tamoxifen induction, one could then challenge these mice with a helminth parasite (e.g., *Nippostrongylus brasiliensis*). The impact of tuft cell-specific *Ptgs1* deletion would be assessed by quantifying worm burden, measuring levels of type 2 cytokines (IL-4, IL-13, IL-25) in the gut tissue, and performing histological analysis to evaluate goblet cell and eosinophil responses compared to control littermates. **Therapeutic Potential:** [PTGS1](/details-gene/5742) is a proven therapeutic target, with inhibition being the primary strategy. However, the constitutive and widespread expression of [PTGS1](/details-gene/5742) for homeostatic functions (e.g., gastric mucosal protection) is the source of major side effects for current non-selective inhibitors. The highly specific expression in cells like tuft cells suggests that cell-type-specific delivery of [PTGS1](/details-gene/5742) inhibitors could offer a more targeted therapeutic approach for inflammatory bowel diseases or allergic conditions, minimizing systemic side effects. Therefore, developing strategies for targeted inhibition, rather than systemic blockade, represents the future of therapeutics aimed at this enzyme.

Genular Protein ID: 1113416111

Symbol: PGH1_HUMAN

Name: Prostaglandin H2 synthase 1

UniProtKB Accession Codes:

P23219 A8K1V7 B4DHQ2 B4E2S5 Q15122 Q3HY28 Q3HY29 Q5T7T6 Q5T7T7 Q5T7T8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 2 CORUM 1 CTD 1 ChEBI 41 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 112 DrugCentral 1 EC 1 EMBL 26 Ensembl 4 ExpressionAtlas 1 GO 17 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MoonDB 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PeroxiBase 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 2 RefSeq 6 Rhea 14 SABIO-RK 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissLipids 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2512924

Title: Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme.

PubMed ID: 2512924

DOI: 10.1016/s0006-291x(89)80049-x

PubMed ID: 1907252

Title: Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment.

PubMed ID: 1907252

DOI: 10.1096/fasebj.5.9.1907252

PubMed ID: 1734857

Title: Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase).

PubMed ID: 1734857

DOI: 10.1016/0006-291x(92)91750-k

PubMed ID: 1587858

Title: Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor beta 1, interleukin 1 beta, and tumor necrosis factor alpha.

PubMed ID: 1587858

DOI: 10.1016/s0021-9258(19)50092-8

PubMed ID: 16141368

Title: Cloning, expression, and functional characterization of human cyclooxygenase-1 splicing variants: evidence for intron 1 retention.

PubMed ID: 16141368

DOI: 10.1124/jpet.105.090944

PubMed ID: 12192304

Title: Characterization of the human prostaglandin H synthase 1 gene (PTGS1): exclusion by genetic linkage analysis as a second modifier gene in familial thrombosis.

PubMed ID: 12192304

DOI: 10.1097/00001721-200209000-00007

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7947975

Title: Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system.

PubMed ID: 7947975

DOI: 10.1016/0167-4838(94)90148-1

PubMed ID: 10966456

Title: Cyclooxygenases: structural, cellular, and molecular biology.

PubMed ID: 10966456

DOI: 10.1146/annurev.biochem.69.1.145

PubMed ID: 24605250

Title: Aspirin, cyclooxygenase inhibition and colorectal cancer.

PubMed ID: 24605250

DOI: 10.4292/wjgpt.v5.i1.40

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 15308583

Title: Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk.

PubMed ID: 15308583

DOI: 10.1093/carcin/bgh260

Sequence Information:

  • Length: 599
  • Mass: 68686
  • Checksum: 1F4F734BCD00346D
  • Sequence:
    • MSRSLLLWFL LFLLLLPPLP VLLADPGAPT PVNPCCYYPC QHQGICVRFG LDRYQCDCTR 
TGYSGPNCTI PGLWTWLRNS LRPSPSFTHF LLTHGRWFWE FVNATFIREM LMRLVLTVRS 
NLIPSPPTYN SAHDYISWES FSNVSYYTRI LPSVPKDCPT PMGTKGKKQL PDAQLLARRF 
LLRRKFIPDP QGTNLMFAFF AQHFTHQFFK TSGKMGPGFT KALGHGVDLG HIYGDNLERQ 
YQLRLFKDGK LKYQVLDGEM YPPSVEEAPV LMHYPRGIPP QSQMAVGQEV FGLLPGLMLY 
ATLWLREHNR VCDLLKAEHP TWGDEQLFQT TRLILIGETI KIVIEEYVQQ LSGYFLQLKF 
DPELLFGVQF QYRNRIAMEF NHLYHWHPLM PDSFKVGSQE YSYEQFLFNT SMLVDYGVEA 
LVDAFSRQIA GRIGGGRNMD HHILHVAVDV IRESREMRLQ PFNEYRKRFG MKPYTSFQEL 
VGEKEMAAEL EELYGDIDAL EFYPGLLLEK CHPNSIFGES MIEIGAPFSL KGLLGNPICS 
PEYWKPSTFG GEVGFNIVKT ATLKKLVCLN TKTCPYVSFR VPDASQDDGP AVERPSTEL

Genular Protein ID: 2629423425

Symbol: A0A087X296_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A087X296

Database IDs:

ARBA 32 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChEBI 41 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 10 Gene3D 2 GeneTree 1 GlyCosmos 1 HGNC 1 InterPro 5 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSR 2 PRINTS 1 PROSITE 3 PROSITE-ProRule 1 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 Rhea 14 SAM 1 SMR 1 SUPFAM 2 UCSC 1 UniPathway 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

Sequence Information:

  • Length: 551
  • Mass: 63286
  • Checksum: 8FB64B70ECFB4662
  • Sequence:
    • MSRSLLLWFL LFLLLLPPLP VLLADPGAPT PVNPCCYYPC QHQGICVRFG LDRYQCDCTR 
TGYSGPNCTI PGLWTWLRNS LRPSPSFTHF LLTHGRWFWE FVNATFIREM LMRLVLTGKK 
QLPDAQLLAR RFLLRRKFIP DPQGTNLMFA FFAQHFTHQF FKTSGKMGPG FTKALGHGVD 
LGHIYGDNLE RQYQLRLFKD GKLKYQVLDG EMYPPSVEEA PVLMHYPRGI PPQSQMAVGQ 
EVFGLLPGLM LYATLWLREH NRVCDLLKAE HPTWGDEQLF QTTRLILIGE TIKIVIEEYV 
QQLSGYFLQL KFDPELLFGV QFQYRNRIAM EFNHLYHWHP LMPDSFKVGS QEYSYEQFLF 
NTSMLVDYGV EALVDAFSRQ IAGRIGGGRN MDHHILHVAV DVIRESREMR LQPFNEYRKR 
FGMKPYTSFQ ELVGEKEMAA ELEELYGDID ALEFYPGLLL EKCHPNSIFG ESMIEIGAPF 
SLKGLLGNPI CSPEYWKPST FGGEVGFNIV KTATLKKLVC LNTKTCPYVS FRVPDASQDD 
GPAVERPSTE L