Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZM027I)

• DOT Name: Complement component C8 gamma chain (C8G)
• Gene Name: C8G
• UniProt ID: CO8G_HUMAN
• PDB ID: 1IW2; 1LF7; 2OVA; 2OVD; 2OVE; 2QOS; 2RD7; 3OJY; 6H03; 6H04; 7NYC; 7NYD; 8B0F; 8B0G; 8B0H
• Pfam ID: PF00061
• Sequence:
  MLPPGTATLLTLLLAAGSLGQKPQRPRRPASPISTIQPKANFDAQQFAGTWLLVAVGSAC
  RFLQEQGHRAEATTLHVAPQGTAMAVSTFRKLDGICWQVRQLYGDTGVLGRFLLQARDAR
  GAVHVVVAETDYQSFAVLYLERAGQLSVKLYARSLPVSDSVLSGFEQRVQEAHLTEDQIF
  YFPKYGFCEAADQFHVLDEVRR
• Function: C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Regulation of actin cytoskeleton (hsa04810)
  Prion disease (hsa05020)
  Amoebiasis (hsa05146)
  Coro.virus disease - COVID-19 (hsa05171)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Regulation of Complement cascade (R-HSA-977606)
  Terminal pathway of complement (R-HSA-166665)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Complement component C8 gamma chain (C8G).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Complement component C8 gamma chain (C8G).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Complement component C8 gamma chain (C8G).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Complement component C8 gamma chain (C8G).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Complement component C8 gamma chain (C8G).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Complement component C8 gamma chain (C8G).	[5]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Complement component C8 gamma chain (C8G).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Complement component C8 gamma chain (C8G).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Complement component C8 gamma chain (C8G).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Complement component C8 gamma chain (C8G).	[2]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
1-anilinonaphthalene-8-sulfonic acid	DMNGY0E	Investigative	1-anilinonaphthalene-8-sulfonic acid affects the binding of Complement component C8 gamma chain (C8G).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Comparative ligand-binding analysis of ten human lipocalins. Biochim Biophys Acta. 2006 Feb;1764(2):161-73. doi: 10.1016/j.bbapap.2005.12.006. Epub 2006 Jan 6.