Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9WF449)

• DOT Name: Kelch repeat and BTB domain-containing protein 12 (KBTBD12)
• Synonyms: Kelch domain-containing protein 6
• Gene Name: KBTBD12
• UniProt ID: KBTBC_HUMAN
• PDB ID: 7QZQ
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MECKIEGKEKYQHSLNLLNKIQNMKELAEMIDVVLTAEGEKFPCHRLVLAAFSPYFKAMF
  TCGLLECNQREVILYDITAESVSVLLNYMYNAALEINNANVQTVAMAAYFMQMEEVFSVC
  QKYMMDHMDASNCLGIYYFAKQIGAEDLSDRSKKYLYQHFAEVSLHEEILEIEVHQFLTL
  IKSDDLNISREESILDLVLRWVNHNKELRTVHLVELLKQVRLELVNPSFLRQALRRNTML
  LCDADCVDIIQNAFKAIKTPQQHSLNLRYGMETTSLLLCIGNNSSGIRSRHRSYGDASFC
  YDPVSRKTYFISSPKYGEGLGTVCTGVVMENNTIIVAGEASASKLSRQKNKNVEIYRYHD
  RGNQFWEKLCTAEFRELYALGSIHNDLYVIGGQMKIKNQYLITNCVDKYSVERDNWKRVS
  PLPLQLACHAVVTVNNKLYVIGGWTPQMDLPDEEPDRLSNKLLQYDPSQDQWSVRAPMKY
  SKYRFSTAVVNSEIYVLGGIGCVGQDKGQVRKCLDVVEIYNPDGDFWREGPPMPSPLLSL
  RTNSTNAGAVDGKLYVCGGFHGADRHEVISKEILELDPWENQWNVVAINVLMHDSYDVCL
  VARMNPRDLIPPPSDLVEEGNEH

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 decreases the methylation of Kelch repeat and BTB domain-containing protein 12 (KBTBD12).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Kelch repeat and BTB domain-containing protein 12 (KBTBD12).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kelch repeat and BTB domain-containing protein 12 (KBTBD12).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Kelch repeat and BTB domain-containing protein 12 (KBTBD12).	[3]

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] 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.
• [3] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [4] 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.