Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOC9OGX)

• DOT Name: Protein AF-17 (MLLT6)
• Synonyms: ALL1-fused gene from chromosome 17 protein
• Gene Name: MLLT6
• Related Disease:
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adult acute monocytic leukemia
  Atrial fibrillation
  Acute leukaemia
• UniProt ID: AF17_HUMAN
• Pfam ID: PF13831 ; PF13832
• Sequence:
  MKEMVGGCCVCSDERGWAENPLVYCDGHACSVAVHQACYGIVQVPTGPWFCRKCESQERA
  ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTC
  YICEEQGRESKAASGACMTCNRHGCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYH
  FSKMKTSRHSSGGGGGGAGGGGGSMGGGGSGFISGRRSRSASPSTQQEKHPTHHERGQKK
  SRKDKERLKQKHKKRPESPPSILTPPVVPTADKVSSSASSSSHHEASTQETSESSRESKG
  KKSSSHSLSHKGKKLSSGKGVSSFTSASSSSSSSSSSSGGPFQPAVSSLQSSPDFSAFPK
  LEQPEEDKYSKPTAPAPSAPPSPSAPEPPKADLFEQKVVFSGFGPIMRFSTTTSSSGRAR
  APSPGDYKSPHVTGSGASAGTHKRMPALSATPVPADETPETGLKEKKHKASKRSRHGPGR
  PKGSRNKEGTGGPAAPSLPSAQLAGFTATAASPFSGGSLVSSGLGGLSSRTFGPSGSLPS
  LSLESPLLGAGIYTSNKDPISHSGGMLRAVCSTPLSSSLLGPPGTSALPRLSRSPFTSTL
  PSSSASISTTQVFSLAGSTFSLPSTHIFGTPMGAVNPLLSQAESSHTEPDLEDCSFRCRG
  TSPQESLSSMSPISSLPALFDQTASAPCGGGQLDPAAPGTTNMEQLLEKQGDGEAGVNIV
  EMLKALHALQKENQRLQEQILSLTAKKERLQILNVQLSVPFPALPAALPAANGPVPGPYG
  LPPQAGSSDSLSTSKSPPGKSSLGLDNSLSTSSEDPHSGCPSRSSSSLSFHSTPPPLPLL
  QQSPATLPLALPGAPAPLPPQPQNGLGRAPGAAGLGAMPMAEGLLGGLAGSGGLPLNGLL
  GGLNGAAAPNPASLSQAGGAPTLQLPGCLNSLTEQQRHLLQQQEQQLQQLQQLLASPQLT
  PEHQTVVYQMIQQIQQKRELQRLQMAGGSQLPMASLLAGSSTPLLSAGTPGLLPTASAPP
  LLPAGALVAPSLGNNTSLMAAAAAAAAVAAAGGPPVLTAQTNPFLSLSGAEGSGGGPKGG
  TADKGASANQEKG

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Adult acute monocytic leukemia	DISG6BLX	Strong	Genetic Variation	[1]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[3]
Acute leukaemia	DISDQFDI	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein AF-17 (MLLT6).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein AF-17 (MLLT6).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein AF-17 (MLLT6).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein AF-17 (MLLT6).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein AF-17 (MLLT6).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein AF-17 (MLLT6).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein AF-17 (MLLT6).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein AF-17 (MLLT6).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein AF-17 (MLLT6).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein AF-17 (MLLT6).	[12]

References

• [1] Identification of a chromosomal breakpoint and detection of a novel form of an MLL-AF17 fusion transcript in acute monocytic leukemia with t(11;17)(q23;q21).Int J Hematol. 2005 Jul;82(1):38-41. doi: 10.1532/IJH97.05025.
• [2] [Application of reverse transcription-multiplex nested PCR to detect MLL rearrangement in AML-M4/M5].Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005 Aug;22(4):444-6.
• [3] Persistent left superior vena cava as an arrhythmogenic source in atrial fibrillation: results from a multicenter experience.J Interv Card Electrophysiol. 2019 Mar;54(2):93-100. doi: 10.1007/s10840-018-0444-x. Epub 2018 Sep 27.
• [4] Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor pathway and its involvement in colorectal carcinogenesis.Cancer Res. 2001 Sep 1;61(17):6345-9.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] 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.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] 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.
• [13] 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.