Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP3JJLW)

• DOT Name: TBC1 domain family member 22A (TBC1D22A)
• Gene Name: TBC1D22A
• Related Disease:
  Bipolar disorder
  Schizophrenia
  Pneumococcal meningitis
• UniProt ID: TB22A_HUMAN
• PDB ID: 2QFZ
• Pfam ID: PF00566
• Sequence:
  MASDGARKQFWKRSNSKLPGSIQHVYGAQHPPFDPLLHGTLLRSTAKMPTTPVKAKRVST
  FQEFESNTSDAWDAGEDDDELLAMAAESLNSEVVMETANRVLRNHSQRQGRPTLQEGPGL
  QQKPRPEAEPPSPPSGDLRLVKSVSESHTSCPAESASDAAPLQRSQSLPHSATVTLGGTS
  DPSTLSSSALSEREASRLDKFKQLLAGPNTDLEELRRLSWSGIPKPVRPMTWKLLSGYLP
  ANVDRRPATLQRKQKEYFAFIEHYYDSRNDEVHQDTYRQIHIDIPRMSPEALILQPKVTE
  IFERILFIWAIRHPASGYVQGINDLVTPFFVVFICEYIEAEEVDTVDVSGVPAEVLCNIE
  ADTYWCMSKLLDGIQDNYTFAQPGIQMKVKMLEELVSRIDEQVHRHLDQHEVRYLQFAFR
  WMNNLLMREVPLRCTIRLWDTYQSEPDGFSHFHLYVCAAFLVRWRKEILEEKDFQELLLF
  LQNLPTAHWDDEDISLLLAEAYRLKFAFADAPNHYKK
• Function: May act as a GTPase-activating protein for Rab family protein(s).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Pneumococcal meningitis	DISM5U0L	Limited	Genetic Variation	[2]

6 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 TBC1 domain family member 22A (TBC1D22A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of TBC1 domain family member 22A (TBC1D22A).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of TBC1 domain family member 22A (TBC1D22A).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of TBC1 domain family member 22A (TBC1D22A).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of TBC1 domain family member 22A (TBC1D22A).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of TBC1 domain family member 22A (TBC1D22A).	[11]

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 TBC1 domain family member 22A (TBC1D22A).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of TBC1 domain family member 22A (TBC1D22A).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of TBC1 domain family member 22A (TBC1D22A).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of TBC1 domain family member 22A (TBC1D22A).	[9]

References

• [1] DNA methylation analyses of the candidate genes identified by a methylome-wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder.Psychiatry Clin Neurosci. 2018 Apr;72(4):245-254. doi: 10.1111/pcn.12645. Epub 2018 Mar 11.
• [2] Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.Nat Commun. 2019 May 15;10(1):2176. doi: 10.1038/s41467-019-09976-3.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.