Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7XMTW8)

• DOT Name: Kelch-like protein 36 (KLHL36)
• Gene Name: KLHL36
• UniProt ID: KLH36_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MMEGSRQTRVSRPYKISESSKVYRWADHSSTVLQRLNEQRLRGLFCDVVLVADEQRVPAH
  RNLLAVCSDYFNSMFTIGMREAFQKEVELIGASYIGLKAVVDFLYGGELVLDGGNIDYVL
  ETAHLLQIWTVVDFCCEYLEQEVSEDNYLYLQELASIYSLKRLDAFIDGFILNHFGTLSF
  TPDFLQNVSMQKLCVYLSSSEVQRECEHDLLQAALQWLTQQPEREAHARQVLENIHFPLI
  PKNDLLHRVKPAVCSLLPKEANCEGFIEEAVRYHNNLAAQPVMQTKRTALRTNQERLLFV
  GGEVSERCLELSDDTCYLDAKSEQWVKETPLPARRSHHCVAVLGGFIFIAGGSFSRDNGG
  DAASNLLYRYDPRCKQWIKVASMNQRRVDFYLASIEDMLVAIGGRNENGALSSVETYSPK
  TDSWSYVAGLPRFTYGHAGTIYKDFVYISGGHDYQIGPYRKNLLCYDHRTDVWEERRPMT
  TARGWHSMCSLGDSIYSIGGSDDNIESMERFDVLGVEAYSPQCNQWTRVAPLLHANSESG
  VAVWEGRIYILGGYSWENTAFSKTVQVYDREADKWSRGVDLPKAIAGGSACVCALEPRPE
  DKKKKGKGKRHQDRGQ
• Function: Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

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 Kelch-like protein 36 (KLHL36).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kelch-like protein 36 (KLHL36).	[8]

7 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 Kelch-like protein 36 (KLHL36).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Kelch-like protein 36 (KLHL36).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kelch-like protein 36 (KLHL36).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Kelch-like protein 36 (KLHL36).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Kelch-like protein 36 (KLHL36).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Kelch-like protein 36 (KLHL36).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Kelch-like protein 36 (KLHL36).	[7]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.