Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC3660I)

• DOT Name: Myelin transcription factor 1 (MYT1)
• Synonyms: MyT1; Myelin transcription factor I; MyTI; PLPB1; Proteolipid protein-binding protein
• Gene Name: MYT1
• Related Disease:
  Multiple sclerosis
  Advanced cancer
  Attention deficit hyperactivity disorder
  Craniofacial microsomia
  Glioblastoma multiforme
  Mental disorder
  Myelodysplastic syndrome
  Neoplasm
  Periventricular leukomalacia
  Alcohol dependence
  Anxiety
  Anxiety disorder
  Restless legs syndrome
  Adult glioblastoma
  Intellectual disability
  Small lymphocytic lymphoma
• UniProt ID: MYT1_HUMAN
• PDB ID: 7Q45
• Pfam ID: PF08474 ; PF01530
• Sequence:
  MSLENEDKRARTRSKALRGPPETTAADLSCPTPGCTGSGHVRGKYSRHRSLQSCPLAKKR
  KLEGAEAEHLVSKRKSHPLKLALDEGYGVDSDGSEDTEVKDASVSDESEGTLEGAEAETS
  GQDEIHRPETAEGRSPVKSHFGSNPIGSATASSKGSYSSYQGIIATSLLNLGQIAEETLV
  EEDLGQAAKPGPGIVHLLQEAAEGAASEEGEKGLFIQPEDAEEVVEVTTERSQDLCPQSL
  EDAASEESSKQKGILSHEEEDEEEEEEEEEEEEDEEEEEEEEEEEEEEEEEEEEEEEEEE
  EEEEEEAAPDVIFQEDTSHTSAQKAPELRGPESPSPKPEYSVIVEVRSDDDKDEDTHSRK
  STVTDESEMQDMMTRGNLGLLEQAIALKAEQVRTVCEPGCPPAEQSQLGLGEPGKAAKPL
  DTVRKSYYSKDPSRAEKREIKCPTPGCDGTGHVTGLYPHHRSLSGCPHKDRIPPEILAMH
  ENVLKCPTPGCTGQGHVNSNRNTHRSLSGCPIAAAEKLAKSHEKQQPQTGDPSKSSSNSD
  RILRPMCFVKQLEVPPYGSYRPNVAPATPRANLAKELEKFSKVTFDYASFDAQVFGKRML
  APKIQTSETSPKAFQCFDYSQDAEAAHMAATAILNLSTRCWEMPENLSTKPQDLPSKSVD
  IEVDENGTLDLSMHKHRKRENAFPSSSSCSSSPGVKSPDASQRHSSTSAPSSSMTSPQSS
  QASRQDEWDRPLDYTKPSRLREEEPEESEPAAHSFASSEADDQEVSEENFEERKYPGEVT
  LTNFKLKFLSKDIKKELLTCPTPGCDGSGHITGNYASHRSLSGCPLADKSLRNLMAAHSA
  DLKCPTPGCDGSGHITGNYASHRSLSGCPRAKKSGVKVAPTKDDKEDPELMKCPVPGCVG
  LGHISGKYASHRSASGCPLAARRQKEGSLNGSSFSWKSLKNEGPTCPTPGCDGSGHANGS
  FLTHRSLSGCPRATFAGKKGKLSGDEVLSPKFKTSDVLENDEEIKQLNQEIRDLNESNSE
  MEAAMVQLQSQISSMEKNLKNIEEENKLIEEQNEALFLELSGLSQALIQSLANIRLPHME
  PICEQNFDAYVSTLTDMYSNQDPENKDLLESIKQAVRGIQV
• Function: Binds to the promoter region of genes encoding proteolipid proteins of the central nervous system. May play a role in the development of neurons and oligodendroglia in the CNS. May regulate a critical transition point in oligodendrocyte lineage development by modulating oligodendrocyte progenitor proliferation relative to terminal differentiation and up-regulation of myelin gene transcription.
• Tissue Specificity: Mostly in developing nervous system. Expressed in neural progenitors and oligodendrocyte lineage cells. More highly expressed in oligodendrocyte progenitors than in differentiated oligodendrocytes.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[3]
Craniofacial microsomia	DISYHJ2P	Strong	GermlineCausalMutation	[4]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[5]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[7]
Periventricular leukomalacia	DIS152XL	Strong	Biomarker	[8]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[9]
Anxiety	DISIJDBA	moderate	Altered Expression	[9]
Anxiety disorder	DISBI2BT	moderate	Altered Expression	[9]
Restless legs syndrome	DISNWY00	moderate	Genetic Variation	[10]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[5]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[11]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[12]

3 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 Myelin transcription factor 1 (MYT1).	[13]
Colchicine	DM2POTE	Approved	Colchicine increases the phosphorylation of Myelin transcription factor 1 (MYT1).	[18]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Myelin transcription factor 1 (MYT1).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Myelin transcription factor 1 (MYT1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Myelin transcription factor 1 (MYT1).	[15]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Myelin transcription factor 1 (MYT1).	[16]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Myelin transcription factor 1 (MYT1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Myelin transcription factor 1 (MYT1).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myelin transcription factor 1 (MYT1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myelin transcription factor 1 (MYT1).	[14]

References

• [1] Myelin transcription factor 1 (Myt1) expression in demyelinated lesions of rodent and human CNS.Glia. 2007 May;55(7):687-97. doi: 10.1002/glia.20492.
• [2] Upregulation of Myt1 Promotes Acquired Resistance of Cancer Cells to Wee1 Inhibition.Cancer Res. 2019 Dec 1;79(23):5971-5985. doi: 10.1158/0008-5472.CAN-19-1961. Epub 2019 Oct 8.
• [3] Acetylcholine-metabolizing butyrylcholinesterase (BCHE) copy number and single nucleotide polymorphisms and their role in attention-deficit/hyperactivity syndrome.J Psychiatr Res. 2013 Dec;47(12):1902-8. doi: 10.1016/j.jpsychires.2013.08.006. Epub 2013 Aug 30.
• [4] Mutations in MYT1, encoding the myelin transcription factor 1, are a rare cause of OAVS.J Med Genet. 2016 Nov;53(11):752-760. doi: 10.1136/jmedgenet-2016-103774. Epub 2016 Jun 29.
• [5] Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors.J Cell Biochem. 2018 Jun;119(6):4644-4655. doi: 10.1002/jcb.26636. Epub 2018 Mar 9.
• [6] Hematopathological alterations of major tumor suppressor cascade, vital cell cycle inhibitors and hematopoietic niche components in experimental myelodysplasia.Chem Biol Interact. 2017 Aug 1;273:1-10. doi: 10.1016/j.cbi.2017.05.014. Epub 2017 May 23.
• [7] Molecular response of 4T1-induced mouse mammary tumours and healthy tissues to zinc treatment.Int J Oncol. 2015 Apr;46(4):1810-8. doi: 10.3892/ijo.2015.2883. Epub 2015 Feb 9.
• [8] Myelin transcription factor 1 (MyT1) immunoreactivity in infants with periventricular leukomalacia.Brain Res Dev Brain Res. 2003 Jan 10;140(1):85-92. doi: 10.1016/s0165-3806(02)00585-0.
• [9] Viral-mediated overexpression of the Myelin Transcription Factor 1 (MyT1) in the dentate gyrus attenuates anxiety- and ethanol-related behaviors in rats.Psychopharmacology (Berl). 2017 Jun;234(12):1829-1840. doi: 10.1007/s00213-017-4588-7. Epub 2017 Mar 16.
• [10] Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis.Lancet Neurol. 2017 Nov;16(11):898-907. doi: 10.1016/S1474-4422(17)30327-7.
• [11] MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions.Am J Med Genet A. 2011 Nov;155A(11):2739-45. doi: 10.1002/ajmg.a.34274. Epub 2011 Oct 11.
• [12] Mitotic slippage: an old tale with a new twist.Cell Cycle. 2019 Jan;18(1):7-15. doi: 10.1080/15384101.2018.1559557. Epub 2019 Jan 2.
• [13] 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.
• [14] Modulation of the expression of bloom helicase by estrogenic agents. Biol Pharm Bull. 2007 Feb;30(2):266-71. doi: 10.1248/bpb.30.266.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] Responses of genes involved in cell cycle control to diverse DNA damaging chemicals in human lung adenocarcinoma A549 cells. Cancer Cell Int. 2005 Aug 24;5:28. doi: 10.1186/1475-2867-5-28.
• [17] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [18] Involvement of cytoskeleton in AhR-dependent CYP1A1 expression. Curr Drug Metab. 2006 Apr;7(3):301-13. doi: 10.2174/138920006776359310.
• [19] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [20] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.