Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTH5A33)

• DOT Name: Kelch-like protein 32 (KLHL32)
• Synonyms: BTB and kelch domain-containing protein 5
• Gene Name: KLHL32
• Related Disease: Chronic obstructive pulmonary disease
• UniProt ID: KLH32_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MPSERCLSIQEMLTGQRLCHSESHNDSVLAALNQQRSDGILCDITLIAEEQKFHAHKAVL
  AACSDYFRAMFSLCMVESGADEVNLHGVTSLGLKQALEFAYTGQILLEPGVIQDVLAAGS
  HLQLLELLNLCSHYLIQELNSFNYLDLYRLADLFNLTLLEKAVIDFLVKHLSELLKSRPE
  EVLTLPYCLLQEVLKSDRLTSLSEEQIWQLAVRWLEHNCHYQYMDELLQYIRFGLMDVDT
  LHTVALSHPLVQASETATALVNEALEYHQSIYAQPVWQTRRTKPRFQSDTLYIIGGKKRE
  VCKVKELRYFNPVDQENALIAAIANWSELAPMPVGRSHHCVAVMGDFLFVAGGEVEHASG
  RTCAVRTACRYDPRSNSWAEIAPMKNCREHFVLGAMEEYLYAVGGRNELRQVLPTVERYC
  PKKNKWTFVQSFDRSLSCHAGYVADGLLWISGGVTNTAQYQNRLMVYEPNQNKWISRSPM
  LQRRVYHSMAAVQRKLYVLGGNDLDYNNDRILVRHIDSYNIDTDQWTRCNFNLLTGQNES
  GVAVHNGRIYLVGGYSIWTNEPLACIQVLDVSREGKEEVFYGPTLPFASNGIAACFLPAP
  YFTCPNLQTLQVPHHRIGTI

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Kelch-like protein 32 (KLHL32).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Kelch-like protein 32 (KLHL32).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Kelch-like protein 32 (KLHL32).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Kelch-like protein 32 (KLHL32).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Kelch-like protein 32 (KLHL32).	[4]

References

• [1] A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
• [2] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.