Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWWJ97D)

• DOT Name: COMM domain-containing protein 7 (COMMD7)
• Gene Name: COMMD7
• Related Disease:
  Cardiovascular disease
  Hepatocellular carcinoma
  Myocardial infarction
  Neoplasm
  Advanced cancer
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
• UniProt ID: COMD7_HUMAN
• PDB ID: 8ESD; 8F2R; 8F2U
• Pfam ID: PF07258 ; PF21672
• Sequence:
  MGRLHCTEDPVPEAVGGDMQQLNQLGAQQFSALTEVLFHFLTEPKEVERFLAQLSEFATT
  NQISLGSLRSIVKSLLLVPNGALKKSLTAKQVQADFITLGLSEEKATYFSEKWKQNAPTL
  ARWAIGQTLMINQLIDMEWKFGVTSGSSELEKVGSIFLQLKLVVKKGNQTENVYIELTLP
  QFYSFLHEMERVRTSMECFC
• Function: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Associates with the NF-kappa-B complex and suppresses its transcriptional activity.
• Tissue Specificity: Widely expressed with highest expression in lung.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[4]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of COMM domain-containing protein 7 (COMMD7).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of COMM domain-containing protein 7 (COMMD7).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of COMM domain-containing protein 7 (COMMD7).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COMM domain-containing protein 7 (COMMD7).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of COMM domain-containing protein 7 (COMMD7).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of COMM domain-containing protein 7 (COMMD7).	[10]

References

• [1] RAPIDSNPs: A new computational pipeline for rapidly identifying key genetic variants reveals previously unidentified SNPs that are significantly associated with individual platelet responses.PLoS One. 2017 Apr 25;12(4):e0175957. doi: 10.1371/journal.pone.0175957. eCollection 2017.
• [2] COMMD7 Regulates NF-B Signaling Pathway in Hepatocellular Carcinoma Stem-like Cells.Mol Ther Oncolytics. 2018 Dec 14;12:112-123. doi: 10.1016/j.omto.2018.12.006. eCollection 2019 Mar 29.
• [3] Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function.Blood. 2010 Nov 25;116(22):4646-56. doi: 10.1182/blood-2010-04-280925. Epub 2010 Sep 10.
• [4] COMMD7 functions as molecular target in pancreatic ductal adenocarcinoma.Mol Carcinog. 2017 Feb;56(2):607-624. doi: 10.1002/mc.22520. Epub 2016 Jul 8.
• [5] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.