Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9Z16M2)

• DOT Name: Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3)
• Synonyms: H-l(3)mbt-like protein 3; L(3)mbt-like protein 3; L3mbt-like 3; MBT-1
• Gene Name: L3MBTL3
• UniProt ID: LMBL3_HUMAN
• PDB ID: 1WJQ; 1WJS; 3UT1; 4FL6; 4L59; 7RTE; 7RTI
• Pfam ID: PF02820 ; PF00536
• Sequence:
  MTESASSTSGQEFDVFSVMDWKDGVGTLPGSDLKFRVNEFGALEVITDENEMENVKKATA
  TTTWMVPTAQEAPTSPPSSRPVFPPAYWTSPPGCPTVFSEKTGMPFRLKDPVKVEGLQFC
  ENCCQYGNVDECLSGGNYCSQNCARHIKDKDQKEERDVEEDNEEEDPKCSRKKKPKLSLK
  ADTKEDGEERDDEMENKQDVRILRGSQRARRKRRGDSAVLKQGLPPKGKKAWCWASYLEE
  EKAVAVPAKLFKEHQSFPYNKNGFKVGMKLEGVDPEHQSVYCVLTVAEVCGYRIKLHFDG
  YSDCYDFWVNADALDIHPVGWCEKTGHKLHPPKGYKEEEFNWQTYLKTCKAQAAPKSLFE
  NQNITVIPSGFRVGMKLEAVDKKNPSFICVATVTDMVDNRFLVHFDNWDESYDYWCEASS
  PHIHPVGWCKEHRRTLITPPGYPNVKHFSWDKYLEETNSLPAPARAFKVKPPHGFQKKMK
  LEVVDKRNPMFIRVATVADTDDHRVKVHFDGWNNCYDYWIDADSPDIHPVGWCSKTGHPL
  QPPLSPLELMEASEHGGCSTPGCKGIGHFKRARHLGPHSAANCPYSEINLNKDRIFPDRL
  SGEMPPASPSFPRNKRTDANESSSSPEIRDQHADDVKEDFEERTESEMRTSHEARGAREE
  PTVQQAQRRSAVFLSFKSPIPCLPLRWEQQSKLLPTVAGIPASKVSKWSTDEVSEFIQSL
  PGCEEHGKVFKDEQIDGEAFLLMTQTDIVKIMSIKLGPALKIFNSILMFKAAEKNSHNEL
• Function: Is a negative regulator of Notch target genes expression, required for RBPJ-mediated transcriptional repression. It recruits KDM1A to Notch-responsive elements and promotes KDM1A-mediated H3K4me demethylation. Involved in the regulation of ubiquitin-dependent degradation of a set of methylated non-histone proteins, including SOX2, DNMT1 and E2F1. It acts as an adapter recruiting the CRL4-DCAF5 E3 ubiquitin ligase complex to methylated target proteins. Required for normal maturation of myeloid progenitor cells.
• KEGG Pathway: Polycomb repressive complex (hsa03083)

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 Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3).	[10]

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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [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] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [10] 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.