Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEJWQ45)

• DOT Name: Choline O-acetyltransferase (CHAT)
• Synonyms: CHOACTase; ChAT; Choline acetylase; EC 2.3.1.6
• Gene Name: CHAT
• Related Disease:
  Congenital myasthenic syndrome 6
  Obsolete presynaptic congenital myasthenic syndrome
• UniProt ID: CLAT_HUMAN
• PDB ID: 2FY2; 2FY3; 2FY4; 2FY5; 7AMD
• EC Number: 2.3.1.6
• Pfam ID: PF00755
• Sequence:
  MGLRTAKKRGLGGGGKWKREEGGGTRGRREVRPACFLQSGGRGDPGDVGGPAGNPGCSPH
  PRAATRPPPLPAHTPAHTPEWCGAASAEAAEPRRAGPHLCIPAPGLTKTPILEKVPRKMA
  AKTPSSEESGLPKLPVPPLQQTLATYLQCMRHLVSEEQFRKSQAIVQQFGAPGGLGETLQ
  QKLLERQEKTANWVSEYWLNDMYLNNRLALPVNSSPAVIFARQHFPGTDDQLRFAASLIS
  GVLSYKALLDSHSIPTDCAKGQLSGQPLCMKQYYGLFSSYRLPGHTQDTLVAQNSSIMPE
  PEHVIVACCNQFFVLDVVINFRRLSEGDLFTQLRKIVKMASNEDERLPPIGLLTSDGRSE
  WAEARTVLVKDSTNRDSLDMIERCICLVCLDAPGGVELSDTHRALQLLHGGGYSKNGANR
  WYDKSLQFVVGRDGTCGVVCEHSPFDGIVLVQCTEHLLKHVTQSSRKLIRADSVSELPAP
  RRLRWKCSPEIQGHLASSAEKLQRIVKNLDFIVYKFDNYGKTFIKKQKCSPDAFIQVALQ
  LAFYRLHRRLVPTYESASIRRFQEGRVDNIRSATPEALAFVRAVTDHKAAVPASEKLLLL
  KDAIRAQTAYTVMAITGMAIDNHLLALRELARAMCKELPEMFMDETYLMSNRFVLSTSQV
  PTTTEMFCCYGPVVPNGYGACYNPQPETILFCISSFHSCKETSSSKFAKAVEESLIDMRD
  LCSLLPPTESKPLATKEKATRPSQGHQP
• Function: Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Cholinergic sy.pse (hsa04725)
• Reactome Pathway:
  Acetylcholine Neurotransmitter Release Cycle (R-HSA-264642)
  Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myasthenic syndrome 6	DIS15H2Z	Strong	Autosomal recessive	[1]
Obsolete presynaptic congenital myasthenic syndrome	DISCATK3	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nicotine	DMWX5CO	Approved	Choline O-acetyltransferase (CHAT) increases the Drug tolerance increased ADR of Nicotine.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Choline O-acetyltransferase (CHAT).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Choline O-acetyltransferase (CHAT).	[4]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Choline O-acetyltransferase (CHAT).	[3]
Methamphetamine	DMPM4SK	Approved	Methamphetamine decreases the activity of Choline O-acetyltransferase (CHAT).	[6]
Scopolamine	DMOM8AL	Approved	Scopolamine decreases the activity of Choline O-acetyltransferase (CHAT).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Choline O-acetyltransferase (CHAT).	[9]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Choline O-acetyltransferase (CHAT).	[10]
Daidzein	DMRFTJX	Investigative	Daidzein increases the activity of Choline O-acetyltransferase (CHAT).	[11]
Elaidoylamide	DMP8VDT	Investigative	Elaidoylamide increases the activity of Choline O-acetyltransferase (CHAT).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Choline O-acetyltransferase (CHAT).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Choline O-acetyltransferase (CHAT).	[8]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Congenital Myasthenic Syndromes Overview. 2003 May 9 [updated 2021 Dec 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [3] Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro. Toxicology. 2023 Mar 15;487:153461. doi: 10.1016/j.tox.2023.153461. Epub 2023 Feb 16.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] Brain choline acetyltransferase activity in chronic, human users of cocaine, methamphetamine, and heroin. Mol Psychiatry. 1999 Jan;4(1):26-32. doi: 10.1038/sj.mp.4000462.
• [7] Effect of Kangshuai Yizhi Formula I on learning and memory dysfunction induced by scopolamine in mice. Chin J Integr Med. 2010 Jun;16(3):252-7.
• [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.
• [9] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [10] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.
• [11] Daidzein activates choline acetyltransferase from MC-IXC cells and improves drug-induced amnesia. Biosci Biotechnol Biochem. 2006 Jan;70(1):107-11.
• [12] Effects of oleamide on choline acetyltransferase and cognitive activities. Biosci Biotechnol Biochem. 2003 Jun;67(6):1284-91.
• [13] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.