Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6482WN)

• DOT Name: Tandem C2 domains nuclear protein (TC2N)
• Synonyms: Membrane targeting tandem C2 domain-containing protein 1; Tandem C2 protein in nucleus; Tac2-N
• Gene Name: TC2N
• Related Disease:
  Breast cancer
  Breast carcinoma
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Venous thromboembolism
  Acute myelogenous leukaemia
• UniProt ID: TAC2N_HUMAN
• Pfam ID: PF00168
• Sequence:
  MATEFIKSCCGGCFYGETEKHNFSVERDFKAAVPNSQNATISVPPLTSVSVKPQLGCTED
  YLLSKLPSDGKEVPFVVPKFKLSYIQPRTQETPSHLEELEGSARASFGDRKVELSSSSQH
  GPSYDVYNPFYMYQHISPDLSRRFPPRSEVKRLYGSVCDLRTNKLPGSPGLSKSMFDLTN
  SSQRFIQRHDSLSSVPSSSSSRKNSQGSNRSLDTITLSGDERDFGRLNVKLFYNSSVEQI
  WITVLQCRDLSWPSSYGDTPTVSIKGILTLPKPVHFKSSAKEGSNAIEFMETFVFAIKLQ
  NLQTVRLVFKIQTQTPRKKTIGECSMSLRTLSTQEMDYSLDITPPSKISVCHAELELGTC
  FQAVNSRIQLQILEARYLPSSSTPLTLSFFVKVGMFSSGELIYKKKTRLLKASNGRVKWG
  ETMIFPLIQSEKEIVFLIKLYSRSSVRRKHFVGQIWISEDSNNIEAVNQWKETVINPEKV
  VIRWHKLNPS

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[4]

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 Tandem C2 domains nuclear protein (TC2N).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tandem C2 domains nuclear protein (TC2N).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tandem C2 domains nuclear protein (TC2N).	[6]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Tandem C2 domains nuclear protein (TC2N).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tandem C2 domains nuclear protein (TC2N).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tandem C2 domains nuclear protein (TC2N).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Tandem C2 domains nuclear protein (TC2N).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tandem C2 domains nuclear protein (TC2N).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Tandem C2 domains nuclear protein (TC2N).	[12]

References

• [1] Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer.Cell Death Dis. 2019 May 29;10(6):424. doi: 10.1038/s41419-019-1663-5.
• [2] TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer.Cell Death Differ. 2019 Jul;26(7):1235-1250. doi: 10.1038/s41418-018-0202-8. Epub 2018 Sep 25.
• [3] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] 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.
• [6] 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.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.