Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0OV12I)

DOT Name Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L)
Synonyms EC 2.1.1.360; DOT1-like protein; Histone H3-K79 methyltransferase; H3-K79-HMTase; Lysine N-methyltransferase 4
Gene Name DOT1L
UniProt ID
DOT1L_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1NW3 ; 2MV7 ; 3QOW ; 3QOX ; 3SR4 ; 3SX0 ; 3UWP ; 4EK9 ; 4EKG ; 4EKI ; 4EQZ ; 4ER0 ; 4ER3 ; 4ER5 ; 4ER6 ; 4ER7 ; 4HRA ; 4WVL ; 5DRT ; 5DRY ; 5DSX ; 5DT2 ; 5DTM ; 5DTQ ; 5DTR ; 5JUW ; 5MVS ; 5MW3 ; 5MW4 ; 6IN3 ; 6J99 ; 6JM9 ; 6JMA ; 6JN2 ; 6NJ9 ; 6NN6 ; 6NOG ; 6NQA ; 6O96 ; 6TE6 ; 6TEL ; 6TEN ; 7BWD ; 7EDP ; 7S7E ; 7S7F ; 7XCR ; 7XCT
EC Number
2.1.1.360
Pfam ID
PF08123
Sequence
MGEKLELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKLAMENYVL
IDYDTKSFESMQRLCDKYNRAIDSIHQLWKGTTQPMKLNTRPSTGLLRHILQQVYNHSVT
DPEKLNNYEPFSPEVYGETSFDLVAQMIDEIKMTDDDLFVDLGSGVGQVVLQVAAATNCK
HHYGVEKADIPAKYAETMDREFRKWMKWYGKKHAEYTLERGDFLSEEWRERIANTSVIFV
NNFAFGPEVDHQLKERFANMKEGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLK
GSVSWTGKPVSYYLHTIDRTILENYFSSLKNPKLREEQEAARRRQQRESKSNAATPTKGP
EGKVAGPADAPMDSGAEEEKAGAATVKKPSPSKARKKKLNKKGRKMAGRKRGRPKKMNTA
NPERKPKKNQTALDALHAQTVSQTAASSPQDAYRSPHSPFYQLPPSVQRHSPNPLLVAPT
PPALQKLLESFKIQYLQFLAYTKTPQYKASLQELLGQEKEKNAQLLGAAQQLLSHCQAQK
EEIRRLFQQKLDELGVKALTYNDLIQAQKEISAHNQQLREQSEQLEQDNRALRGQSLQLL
KARCEELQLDWATLSLEKLLKEKQALKSQISEKQRHCLELQISIVELEKSQRQQELLQLK
SCVPPDDALSLHLRGKGALGRELEPDASRLHLELDCTKFSLPHLSSMSPELSMNGQAAGY
ELCGVLSRPSSKQNTPQYLASPLDQEVVPCTPSHVGRPRLEKLSGLAAPDYTRLSPAKIV
LRRHLSQDHTVPGRPAASELHSRAEHTKENGLPYQSPSVPGSMKLSPQDPRPLSPGALQL
AGEKSSEKGLRERAYGSSGELITSLPISIPLSTVQPNKLPVSIPLASVVLPSRAERARST
PSPVLQPRDPSSTLEKQIGANAHGAGSRSLALAPAGFSYAGSVAISGALAGSPASLTPGA
EPATLDESSSSGSLFATVGSRSSTPQHPLLLAQPRNSLPASPAHQLSSSPRLGGAAQGPL
PEASKGDLPSDSGFSDPESEAKRRIVFTITTGAGSAKQSPSSKHSPLTASARGDCVPSHG
QDSRRRGRRKRASAGTPSLSAGVSPKRRALPSVAGLFTQPSGSPLNLNSMVSNINQPLEI
TAISSPETSLKSSPVPYQDHDQPPVLKKERPLSQTNGAHYSPLTSDEEPGSEDEPSSARI
ERKIATISLESKSPPKTLENGGGLAGRKPAPAGEPVNSSKWKSTFSPISDIGLAKSADSP
LQASSALSQNSLFTFRPALEEPSADAKLAAHPRKGFPGSLSGADGLSPGTNPANGCTFGG
GLAADLSLHSFSDGASLPHKGPEAAGLSSPLSFPSQRGKEGSDANPFLSKRQLDGLAGLK
GEGSRGKEAGEGGLPLCGPTDKTPLLSGKAAKARDREVDLKNGHNLFISAAAVPPGSLLS
GPGLAPAASSAGGAASSAQTHRSFLGPFPPGPQFALGPMSLQANLGSVAGSSVLQSLFSS
VPAAAGLVHVSSAATRLTNSHAMGSFSGVAGGTVGGN
Function Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
KEGG Pathway
Lysine degradation (hsa00310 )
Metabolic pathways (hsa01100 )
Transcriptio.l misregulation in cancer (hsa05202 )
Reactome Pathway
PKMTs methylate histone lysines (R-HSA-3214841 )
BioCyc Pathway
MetaCyc:HS02643-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [8]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [8]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid affects the phosphorylation of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [10]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [2]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [3]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [4]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [5]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [7]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L). [9]
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⏷ Show the Full List of 6 Drug(s)

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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
3 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
4 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
5 Association of H3K79 monomethylation (an epigenetic signature) with arsenic-induced skin lesions. Mutat Res. 2018 Jan;807:1-9. doi: 10.1016/j.mrfmmm.2017.11.001. Epub 2017 Nov 14.
6 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.
7 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
8 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.
9 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
10 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.