Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJBP3VJ)

• DOT Name: Transgelin-3 (TAGLN3)
• Synonyms: Neuronal protein 22; NP22; Neuronal protein NP25
• Gene Name: TAGLN3
• Related Disease:
  Alcohol dependence
  Schizophrenia
• UniProt ID: TAGL3_HUMAN
• Pfam ID: PF00402 ; PF00307
• Sequence:
  MANRGPSYGLSREVQEKIEQKYDADLENKLVDWIILQCAEDIEHPPPGRAHFQKWLMDGT
  VLCKLINSLYPPGQEPIPKISESKMAFKQMEQISQFLKAAETYGVRTTDIFQTVDLWEGK
  DMAAVQRTLMALGSVAVTKDDGCYRGEPSWFHRKAQQNRRGFSEEQLRQGQNVIGLQMGS
  NKGASQAGMTGYGMPRQIM
• Tissue Specificity: Widely expressed in the brain. Expression is increased in the superior frontal cortex of alcoholics, but not in the motor cortex or cerebellum.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Transgelin-3 (TAGLN3) affects the response to substance of Daunorubicin.	[18]

15 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 Transgelin-3 (TAGLN3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transgelin-3 (TAGLN3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transgelin-3 (TAGLN3).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transgelin-3 (TAGLN3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transgelin-3 (TAGLN3).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transgelin-3 (TAGLN3).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transgelin-3 (TAGLN3).	[8]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Transgelin-3 (TAGLN3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transgelin-3 (TAGLN3).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transgelin-3 (TAGLN3).	[11]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Transgelin-3 (TAGLN3).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transgelin-3 (TAGLN3).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transgelin-3 (TAGLN3).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transgelin-3 (TAGLN3).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Transgelin-3 (TAGLN3).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transgelin-3 (TAGLN3).	[13]

References

• [1] Changes in neuronal protein 22 expression and cytoskeletal association in the alcohol-dependent and withdrawn rat brain.J Neurosci Res. 2005 Jul 15;81(2):253-60. doi: 10.1002/jnr.20563.
• [2] Expression of human neuronal protein 22, a novel cytoskeleton-associated protein, was decreased in the anterior cingulate cortex of schizophrenia.Neurosci Lett. 2005 Apr 22;378(3):125-30. doi: 10.1016/j.neulet.2004.12.079.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [13] 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.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [18] Mapping genes that contribute to daunorubicin-induced cytotoxicity. Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.