Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTTUH2W)

• DOT Name: Tropomodulin-2 (TMOD2)
• Synonyms: Neuronal tropomodulin; N-Tmod
• Gene Name: TMOD2
• Related Disease:
  Advanced cancer
  Transitional cell carcinoma
• UniProt ID: TMOD2_HUMAN
• Pfam ID: PF03250
• Sequence:
  MALPFQKELEKYKNIDEDELLGKLSEEELKQLENVLDDLDPESAMLPAGFRQKDQTQKAA
  TGPFDREHLLMYLEKEALEQKDREDFVPFTGEKKGRVFIPKEKPIETRKEEKVTLDPELE
  EALASASDTELYDLAAVLGVHNLLNNPKFDEETANNKGGKGPVRNVVKGEKVKPVFEEPP
  NPTNVEISLQQMKANDPSLQEVNLNNIKNIPIPTLREFAKALETNTHVKKFSLAATRSND
  PVAIAFADMLKVNKTLTSLNIESNFITGTGILALVEALKENDTLTEIKIDNQRQQLGTAV
  EMEIAQMLEENSRILKFGYQFTKQGPRTRVAAAITKNNDLVRKKRVEADRR
• Function: Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton.
• Tissue Specificity: Neuronal-tissue specific.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Tropomodulin-2 (TMOD2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tropomodulin-2 (TMOD2).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tropomodulin-2 (TMOD2).	[6]
Docetaxel	DMDI269	Approved	Docetaxel decreases the expression of Tropomodulin-2 (TMOD2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tropomodulin-2 (TMOD2).	[9]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin increases the expression of Tropomodulin-2 (TMOD2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tropomodulin-2 (TMOD2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tropomodulin-2 (TMOD2).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tropomodulin-2 (TMOD2).	[12]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Tropomodulin-2 (TMOD2).	[7]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of Tropomodulin-2 (TMOD2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Tropomodulin-2 (TMOD2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tropomodulin-2 (TMOD2).	[8]

References

• [1] Profiling of transcripts and proteins modulated by K-ras oncogene in the lung tissues of K-ras transgenic mice by omics approaches.Int J Oncol. 2009 Jan;34(1):161-72.
• [2] Alterations in tropomyosin isoform expression in human transitional cell carcinoma of the urinary bladder.Int J Cancer. 2004 Jun 20;110(3):368-73. doi: 10.1002/ijc.20151.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [11] 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.
• [12] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.