Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU7GPKK)

• DOT Name: Tumor protein p63-regulated gene 1-like protein (TPRG1L)
• Synonyms: Mossy fiber terminal-associated vertebrate-specific presynaptic protein; Protein FAM79A
• Gene Name: TPRG1L
• Related Disease:
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Non-insulin dependent diabetes
• UniProt ID: TPRGL_HUMAN
• Pfam ID: PF12456
• Sequence:
  MLQLRDSVDSAGTSPTAVLAAGEEVGAGGGPGGGRPGAGTPLRQTLWPLSIHDPTRRARV
  KEYFVFRPGSIEQAVEEIRVVVRPVEDGEIQGVWLLTEVDHWNNEKERLVLVTEQSLLIC
  KYDFISLQCQQVVRIALNAVDTISYGEFQFPPKSLNKREGFGIRIQWDKQSRPSFINRWN
  PWSTNVPYATFTEHPMAGADEKTASLCQLESFKALLIQAVKKAQKESPLPGQANGVLILE
  RPLLIETYVGLMSFINNEAKLGYSMTRGKIGF
• Function: Presynaptic protein involved in the synaptic transmission tuning. Regulates synaptic release probability by decreasing the calcium sensitivity of release.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[2]

2 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 Tumor protein p63-regulated gene 1-like protein (TPRG1L).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tumor protein p63-regulated gene 1-like protein (TPRG1L).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tumor protein p63-regulated gene 1-like protein (TPRG1L).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tumor protein p63-regulated gene 1-like protein (TPRG1L).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Tumor protein p63-regulated gene 1-like protein (TPRG1L).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tumor protein p63-regulated gene 1-like protein (TPRG1L).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tumor protein p63-regulated gene 1-like protein (TPRG1L).	[5]

References

• [1] LncRNA LCPAT1 Mediates Smoking/ Particulate Matter 2.5-Induced Cell Autophagy and Epithelial-Mesenchymal Transition in Lung Cancer Cells via RCC2.Cell Physiol Biochem. 2018;47(3):1244-1258. doi: 10.1159/000490220. Epub 2018 Jun 15.
• [2] TERC promotes cellular inflammatory response independent of telomerase.Nucleic Acids Res. 2019 Sep 5;47(15):8084-8095. doi: 10.1093/nar/gkz584.
• [3] 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.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [7] 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.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.