Molecule Information

General Information of the Molecule (ID: Mol01896)

• Name: Prostaglandin-endoperoxide synthase 1 (PTGS1) ,Homo sapiens
• Synonyms: MT-CO1; COI; COXI; MTCO1
• Molecule Type: Protein
• Gene Name: PTGS1
• Gene ID: 4512
• Sequence:
  MFADRWLFSTNHKDIGTLYLLFGAWAGVLGTALSLLIRAELGQPGNLLGNDHIYNVIVTA
  HAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLLLLLASAMVEA
  GAGTGWTVYPPLAGNYSHPGASVDLTIFSLHLAGVSSILGAINFITTIINMKPPAMTQYQ
  TPLFVWSVLITAVLLLLSLPVLAAGITMLLTDRNLNTTFFDPAGGGDPILYQHLFWFFGH
  PEVYILILPGFGMISHIVTYYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD
  TRAYFTSATMIIAIPTGVKVFSWLATLHGSNMKWSAAVLWALGFIFLFTVGGLTGIVLAN
  SSLDIVLHDTYYVVAHFHYVLSMGAVFAIMGGFIHWFPLFSGYTLDQTYAKIHFTIMFIG
  VNLTFFPQHFLGLSGMPRRYSDYPDAYTTWNILSSVGSFISLTAVMLMIFMIWEAFASKR
  KVLMVEEPSMNLEWLYGCPPPYHTFEEPVYMKS
• Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
• Uniprot ID: COX1_HUMAN
• HGNC ID: HGNC:9604

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Aspirin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Acute myocardial infarction [1]

• Resistant Disease: Acute myocardial infarction [ICD-11: BA41.1]
• Resistant Drug: Aspirin
• Molecule Alteration: Missense mutation; p.C50T+p.A842G+p.A1676G
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The following factors contribute to aspirin resistance: the COX-1 polymorphisms of C50T, -A842G, and A1676G; the COX-2 polymorphism of -765.

Disease Class: Hypo-attenuated leaflet thickening [2]

• Resistant Disease: Hypo-attenuated leaflet thickening [ICD-11: BD10.2]
• Resistant Drug: Aspirin
• Molecule Alteration: SNP; rs10306114
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01).

Disease Class: Dysmenorrhea [3]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Resistant Drug: Aspirin
• Molecule Alteration: SNP; rs10306114
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Genetic polymorphisms have been shown to disrupt COX-1 inhibition with aspirin. For example, Ulehlova et al demonstrated that COX-1 polymorphism rs10306114 was correlated with high platelet aggregation in aspirin-resistant individuals.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 11

Myocardial infarction [ICD-11: BA41]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Peripheral blood
• The Specified Disease: Myocardial infarction
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.82E-01; Fold-change: -3.91E-02; Z-score: -1.04E-01

References

• Ref 1: Assessment of Risk Factors for Drug Resistance of Dual Anti Platelet Therapy After PCI .Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221083674. doi: 10.1177/10760296221083674. 10.1177/10760296221083674
• Ref 2: Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement .J Thromb Thrombolysis. 2018 Apr;45(3):463-465. doi: 10.1007/s11239-018-1636-z. 10.1007/s11239-018-1636-z
• Ref 3: Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment .Am J Obstet Gynecol. 2018 Apr;218(4):390-400. doi: 10.1016/j.ajog.2017.08.108. Epub 2017 Sep 6. 10.1016/j.ajog.2017.08.108