Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTTHS89)

• DOT Name: BTB/POZ domain-containing protein KCTD5 (KCTD5)
• Gene Name: KCTD5
• UniProt ID: KCTD5_HUMAN
• PDB ID: 3DRX; 3DRY; 3DRZ; 8U7Z; 8U80; 8U81; 8U82; 8U83; 8U84
• Pfam ID: PF02214
• Sequence:
  MAENHCELLSPARGGIGAGLGGGLCRRCSAGLGALAQRPGSVSKWVRLNVGGTYFLTTRQ
  TLCRDPKSFLYRLCQADPDLDSDKDETGAYLIDRDPTYFGPVLNYLRHGKLVINKDLAEE
  GVLEEAEFYNITSLIKLVKDKIRERDSKTSQVPVKHVYRVLQCQEEELTQMVSTMSDGWK
  FEQLVSIGSSYNYGNEDQAEFLCVVSKELHNTPYGTASEPSEKAKILQERGSRM
• Function: Its interaction with CUL3 suggests that it may act as a substrate adapter in some E3 ligase complex. Does not affect the function of Kv channel Kv2.1/KCNB1, Kv1.2/KCNA2, Kv4.2/KCND2 and Kv3.4/KCNC4.

Molecular Interaction Atlas (MIA) of This DOT

2 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 BTB/POZ domain-containing protein KCTD5 (KCTD5).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of BTB/POZ domain-containing protein KCTD5 (KCTD5).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of BTB/POZ domain-containing protein KCTD5 (KCTD5).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BTB/POZ domain-containing protein KCTD5 (KCTD5).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of BTB/POZ domain-containing protein KCTD5 (KCTD5).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of BTB/POZ domain-containing protein KCTD5 (KCTD5).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BTB/POZ domain-containing protein KCTD5 (KCTD5).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of BTB/POZ domain-containing protein KCTD5 (KCTD5).	[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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [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.