Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXYO2R9)

• DOT Name: Kelch-like protein 8 (KLHL8)
• Gene Name: KLHL8
• UniProt ID: KLHL8_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MASDSMSSKQARNHITKGKRQQQHQQIKNRSSISDGDGEDSFIFEANEAWKDFHGSLLRF
  YENGELCDVTLKVGSKLISCHKLVLACVIPYFRAMFLSEMAEAKQTLIEIRDFDGDAIED
  LVKFVYSSRLTLTVDNVQPLLYAACILQVELVARACCEYMKLHFHPSNCLAVRAFAESHN
  RIDLMDMADQYACDHFTEVVECEDFVSVSPQHLHKLLSSSDLNIENEKQVYNAAIKWLLA
  NPQHHSKWLDETLAQVRLPLLPVDFLMGVVAKEQIVKQNLKCRDLLDEARNYHLHLSSRA
  VPDFEYSIRTTPRKHTAGVLFCVGGRGGSGDPFRSIECYSINKNSWFFGPEMNSRRRHVG
  VISVEGKVYAVGGHDGNEHLGSMEMFDPLTNKWMMKASMNTKRRGIALASLGGPIYAIGG
  LDDNTCFNDVERYDIESDQWSTVAPMNTPRGGVGSVALVNHVYAVGGNDGMASLSSVERY
  DPHLDKWIEVKEMGQRRAGNGVSKLHGCLYVVGGFDDNSPLSSVERYDPRSNKWDYVAAL
  TTPRGGVGIATVMGKIFAVGGHNGNAYLNTVEAFDPVLNRWELVGSVSHCRAGAGVAVCS
  CLTSQIRDVGHGSNNVVDCM
• Function: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for The BCR(KLHL8) ubiquitin ligase complex mediates ubiquitination and degradation of RAPSN.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Kelch-like protein 8 (KLHL8).	[1]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Kelch-like protein 8 (KLHL8).	[2]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Kelch-like protein 8 (KLHL8).	[4]

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 decreases the methylation of Kelch-like protein 8 (KLHL8).	[3]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [3] 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.
• [4] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.