Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3WGPR3)

• DOT Name: Platelet glycoprotein V (GP5)
• Synonyms: GPV; Glycoprotein 5; CD antigen CD42d
• Gene Name: GP5
• Related Disease:
  Arterial thrombosis
  Autoimmune thrombocytopenia
  Cardiovascular disease
  Idiopathic thrombocytopenic purpura
  Immune thrombocytopenia
  Thrombocytopenia
  Ebola virus infection
• UniProt ID: GPV_HUMAN
• Pfam ID: PF13855 ; PF01463
• Sequence:
  MLRGTLLCAVLGLLRAQPFPCPPACKCVFRDAAQCSGGDVARISALGLPTNLTHILLFGM
  GRGVLQSQSFSGMTVLQRLMISDSHISAVAPGTFSDLIKLKTLRLSRNKITHLPGALLDK
  MVLLEQLFLDHNALRGIDQNMFQKLVNLQELALNQNQLDFLPASLFTNLENLKLLDLSGN
  NLTHLPKGLLGAQAKLERLLLHSNRLVSLDSGLLNSLGALTELQFHRNHIRSIAPGAFDR
  LPNLSSLTLSRNHLAFLPSALFLHSHNLTLLTLFENPLAELPGVLFGEMGGLQELWLNRT
  QLRTLPAAAFRNLSRLRYLGVTLSPRLSALPQGAFQGLGELQVLALHSNGLTALPDGLLR
  GLGKLRQVSLRRNRLRALPRALFRNLSSLESVQLDHNQLETLPGDVFGALPRLTEVLLGH
  NSWRCDCGLGPFLGWLRQHLGLVGGEEPPRCAGPGAHAGLPLWALPGGDAECPGPRGPPP
  RPAADSSSEAPVHPALAPNSSEPWVWAQPVTTGKGQDHSPFWGFYFLLLAVQAMITVIIV
  FAMIKIGQLFRKLIRERALG
• Function: The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis.
• Tissue Specificity: Platelets and megakaryocytes.
• KEGG Pathway:
  ECM-receptor interaction (hsa04512)
  Platelet activation (hsa04611)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway:
  GP1b-IX-V activation signalling (R-HSA-430116)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  Platelet Aggregation (Plug Formation) (R-HSA-76009)
  Defective F9 activation (R-HSA-9673221)
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arterial thrombosis	DIS2LR4O	Strong	Genetic Variation	[1]
Autoimmune thrombocytopenia	DISNF0OI	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[3]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Biomarker	[2]
Immune thrombocytopenia	DISVCBNS	Strong	Biomarker	[2]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[2]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion increases the expression of Platelet glycoprotein V (GP5).	[5]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Platelet glycoprotein V (GP5).	[7]

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 decreases the methylation of Platelet glycoprotein V (GP5).	[6]

References

• [1] The GPIIIa (beta3 integrin) PlA polymorphism in the early development of coronary atherosclerosis.Atherosclerosis. 2001 Feb 15;154(3):721-7. doi: 10.1016/s0021-9150(00)00683-3.
• [2] Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia.Haematologica. 2019 Jun;104(6):1237-1243. doi: 10.3324/haematol.2018.211086. Epub 2019 Mar 28.
• [3] Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases.Sci Rep. 2017 Feb 22;7:42870. doi: 10.1038/srep42870.
• [4] Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection.Antiviral Res. 2016 Mar;127:20-31. doi: 10.1016/j.antiviral.2016.01.001. Epub 2016 Jan 9.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.