Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4IE8DV)

• DOT Name: Platelet glycoprotein VI (GP6)
• Synonyms: GPVI; Glycoprotein 6
• Gene Name: GP6
• Related Disease: Platelet-type bleeding disorder 11
• UniProt ID: GPVI_HUMAN
• PDB ID: 2GI7; 5OU7; 5OU8; 5OU9; 7NMU; 7R58
• Pfam ID: PF13895 ; PF13927
• Sequence:
  MSPSPTALFCLGLCLGRVPAQSGPLPKPSLQALPSSLVPLEKPVTLRCQGPPGVDLYRLE
  KLSSSRYQDQAVLFIPAMKRSLAGRYRCSYQNGSLWSLPSDQLELVATGVFAKPSLSAQP
  GPAVSSGGDVTLQCQTRYGFDQFALYKEGDPAPYKNPERWYRASFPIITVTAAHSGTYRC
  YSFSSRDPYLWSAPSDPLELVVTGTSVTPSRLPTEPPSPVAEFSEATAELTVSFTNEVFT
  TETSRSITASPKESDSPAGPARQYYTKGNLVRICLGAVILIILAGFLAEDWHSRRKRLRH
  RGRAVQRPLPPLPPLPLTRKSNGGQDGGRQDVHSRGLCS
• Function: Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely FYN or LYN) and SYK, the adapter protein LAT and leads to the activation of PLCG2.
• Tissue Specificity: Megakaryocytes and platelets.
• KEGG Pathway:
  ECM-receptor interaction (hsa04512)
  Platelet activation (hsa04611)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Platelet-type bleeding disorder 11	DISZU4YT	Definitive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Platelet glycoprotein VI (GP6) decreases the response to substance of Aspirin.	[4]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Platelet glycoprotein VI (GP6).	[2]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Platelet glycoprotein VI (GP6).	[3]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [3] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [4] Polymorphisms of COX-1 and GPVI associate with the antiplatelet effect of aspirin in coronary artery disease patients. Thromb Haemost. 2006 Feb;95(2):253-9. doi: 10.1160/TH05-07-0516.