Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ27VJN)

• DOT Name: Complement component C7 (C7)
• Gene Name: C7
• Related Disease:
  Acute otitis media
  Arthritis
  Complement component 7 deficiency
  Complement deficiency
  Membranous glomerulonephritis
  Meningococcal disease
  Meningococcal meningitis
  Otitis media
  Myocardial infarction
• UniProt ID: CO7_HUMAN
• PDB ID: 2WCY; 6H03; 6H04; 7NYC; 7NYD; 8B0F; 8B0G; 8B0H
• Pfam ID: PF21284 ; PF21330 ; PF18434 ; PF00057 ; PF01823 ; PF00084 ; PF00090
• Sequence:
  MKVISLFILVGFIGEFQSFSSASSPVNCQWDFYAPWSECNGCTKTQTRRRSVAVYGQYGG
  QPCVGNAFETQSCEPTRGCPTEEGCGERFRCFSGQCISKSLVCNGDSDCDEDSADEDRCE
  DSERRPSCDIDKPPPNIELTGNGYNELTGQFRNRVINTKSFGGQCRKVFSGDGKDFYRLS
  GNVLSYTFQVKINNDFNYEFYNSTWSYVKHTSTEHTSSSRKRSFFRSSSSSSRSYTSHTN
  EIHKGKSYQLLVVENTVEVAQFINNNPEFLQLAEPFWKELSHLPSLYDYSAYRRLIDQYG
  THYLQSGSLGGEYRVLFYVDSEKLKQNDFNSVEEKKCKSSGWHFVVKFSSHGCKELENAL
  KAASGTQNNVLRGEPFIRGGGAGFISGLSYLELDNPAGNKRRYSAWAESVTNLPQVIKQK
  LTPLYELVKEVPCASVKKLYLKWALEEYLDEFDPCHCRPCQNGGLATVEGTHCLCHCKPY
  TFGAACEQGVLVGNQAGGVDGGWSCWSSWSPCVQGKKTRSRECNNPPPSGGGRSCVGETT
  ESTQCEDEELEHLRLLEPHCFPLSLVPTEFCPSPPALKDGFVQDEGTMFPVGKNVVYTCN
  EGYSLIGNPVARCGEDLRWLVGEMHCQKIACVLPVLMDGIQSHPQKPFYTVGEKVTVSCS
  GGMSLEGPSAFLCGSSLKWSPEMKNARCVQKENPLTQAVPKCQRWEKLQNSRCVCKMPYE
  CGPSLDVCAQDERSKRILPLTVCKMHVLHCQGRNYTLTGRDSCTLPASAEKACGACPLWG
  KCDAESSKCVCREASECEEEGFSICVEVNGKEQTMSECEAGALRCRGQSISVTSIRPCAA
  ETQ
• Function: Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C7 serves as a membrane anchor.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Regulation of actin cytoskeleton (hsa04810)
  Prion disease (hsa05020)
  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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute otitis media	DISL8D8G	Strong	Biomarker	[1]
Arthritis	DIST1YEL	Strong	Biomarker	[2]
Complement component 7 deficiency	DIST3K9E	Strong	Autosomal recessive	[3]
Complement deficiency	DISGN469	Strong	Biomarker	[3]
Membranous glomerulonephritis	DISFSUKQ	Strong	Biomarker	[4]
Meningococcal disease	DISGDM2Z	Strong	Biomarker	[5]
Meningococcal meningitis	DISCKTAT	Strong	Biomarker	[2]
Otitis media	DISGZDUO	Strong	Biomarker	[1]
Myocardial infarction	DIS655KI	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Complement component C7 (C7).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Complement component C7 (C7).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Complement component C7 (C7).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Complement component C7 (C7).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Complement component C7 (C7).	[11]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Complement component C7 (C7).	[12]
Tubocurarine	DMBZIVP	Approved	Tubocurarine decreases the expression of Complement component C7 (C7).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Complement component C7 (C7).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Complement component C7 (C7).	[15]

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 increases the methylation of Complement component C7 (C7).	[13]

References

• [1] How partial C7 deficiency with chronic and recurrent bacterial infections can mimic total C7 deficiency: temporary restoration of host C7 levels following plasma transfusion.Immunology. 1996 Jul;88(3):407-11. doi: 10.1046/j.1365-2567.1996.d01-663.x.
• [2] Familial deficiency of the seventh component of complement associated with recurrent bacteremic infections due to Neisseria.J Infect Dis. 1978 Sep;138(3):359-68. doi: 10.1093/infdis/138.3.359.
• [3] Complement component C7 deficiency in two Spanish families. Immunology. 2004 Dec;113(4):518-23. doi: 10.1111/j.1365-2567.2004.01997.x.
• [4] Detection of terminal complement components in experimental immune glomerular injury.Kidney Int. 1984 Dec;26(6):830-7. doi: 10.1038/ki.1984.225.
• [5] Two mutations of the C7 gene, c.1424G > A and c.281-1G > T, in two Korean families.J Clin Immunol. 2006 Mar;26(2):186-91. doi: 10.1007/s10875-006-9006-6. Epub 2006 Mar 22.
• [6] Time course studies on the initiation of complement activation in acute myocardial infarction induced by coronary artery ligation in rats.Mol Cell Biochem. 2005 Jan;268(1-2):149-58. doi: 10.1007/s11010-005-3856-8.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire. Reprod Toxicol. 2017 Oct;73:184-195. doi: 10.1016/j.reprotox.2017.07.023. Epub 2017 Aug 6.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [12] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [13] 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.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.