Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GG8ED)

• DOT Name: Troponin I, slow skeletal muscle (TNNI1)
• Synonyms: Troponin I, slow-twitch isoform
• Gene Name: TNNI1
• Related Disease:
  Acute coronary syndrome
  Calcinosis
  Coronary ischemia
  Non-small-cell lung cancer
• UniProt ID: TNNI1_HUMAN
• Pfam ID: PF00992
• Sequence:
  MPEVERKPKITASRKLLLKSLMLAKAKECWEQEHEEREAEKVRYLAERIPTLQTRGLSLS
  ALQDLCRELHAKVEVVDEERYDIEAKCLHNTREIKDLKLKVMDLRGKFKRPPLRRVRVSA
  DAMLRALLGSKHKVSMDLRANLKSVKKEDTEKERPVEVGDWRKNVEAMSGMEGRKKMFDA
  AKSPTSQ
• Function: Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
• Tissue Specificity: Highest levels observed in human skeletal muscle (e.g. gastrocnemious muscle), differentiated cultures of primary human muscle cells and rhabdomyosarcoma cells cultured in low serum medium. Expressed in C2 muscle cell myoblasts and myotubes.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute coronary syndrome	DIS7DYEW	Strong	Altered Expression	[1]
Calcinosis	DISQP4OR	Strong	Altered Expression	[2]
Coronary ischemia	DISDJJ5G	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Troponin I, slow skeletal muscle (TNNI1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Troponin I, slow skeletal muscle (TNNI1).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Troponin I, slow skeletal muscle (TNNI1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Troponin I, slow skeletal muscle (TNNI1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Troponin I, slow skeletal muscle (TNNI1).	[9]

2 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 increases the methylation of Troponin I, slow skeletal muscle (TNNI1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Troponin I, slow skeletal muscle (TNNI1).	[10]

References

• [1] Myocardial injury in critically ill patients: relation to increased cardiac troponin I and hospital mortality.Chest. 2005 Oct;128(4):2758-64. doi: 10.1378/chest.128.4.2758.
• [2] Increased serum levels of troponin I and lesions in coronary angiography in hemodialysed patients.Rocz Akad Med Bialymst. 2005;50:311-3.
• [3] Troponin-I enhances and is required for oncogenic overgrowth.Oncotarget. 2016 Aug 16;7(33):52631-52642. doi: 10.18632/oncotarget.10616.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] 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.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] 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.