Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP5R5QI)

• DOT Name: COMM domain-containing protein 2 (COMMD2)
• Gene Name: COMMD2
• UniProt ID: COMD2_HUMAN
• PDB ID: 8F2R; 8F2U
• Pfam ID: PF07258
• Sequence:
  MLLELSEEHKEHLAFLPQVDSAVVAEFGRIAVEFLRRGANPKIYEGAARKLNVSSDTVQH
  GVEGLTYLLTESSKLMISELDFQDSVFVLGFSEELNKLLLQLYLDNRKEIRTILSELAPS
  LPSYHNLEWRLDVQLASRSLRQQIKPAVTIKLHLNQNGDHNTKVLQTDPATLLHLVQQLE
  QALEEMKTNHCRRVVRNIK
• Function: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of COMM domain-containing protein 2 (COMMD2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of COMM domain-containing protein 2 (COMMD2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of COMM domain-containing protein 2 (COMMD2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of COMM domain-containing protein 2 (COMMD2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COMM domain-containing protein 2 (COMMD2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of COMM domain-containing protein 2 (COMMD2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of COMM domain-containing protein 2 (COMMD2).	[8]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of COMM domain-containing protein 2 (COMMD2).	[9]

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 COMM domain-containing protein 2 (COMMD2).	[6]

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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] 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.