Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5RU5G6)

DOT Name Tropomyosin alpha-3 chain (TPM3)
Synonyms Gamma-tropomyosin; Tropomyosin-3; Tropomyosin-5; hTM5
Gene Name TPM3
Related Disease
Glioblastoma multiforme ( )
Thyroid cancer ( )
TPM3-related myopathy ( )
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Anaplastic large cell lymphoma ( )
Autoimmune disease ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Clear cell renal carcinoma ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Congenital myopathy 4A, autosomal dominant ( )
Congenital myopathy 4B, autosomal recessive ( )
Gastric cancer ( )
Gastric neoplasm ( )
Glioma ( )
Hepatocellular carcinoma ( )
Hereditary diffuse gastric adenocarcinoma ( )
Leukemia ( )
Lung cancer ( )
Mammary analogue secretory carcinoma ( )
Melanoma ( )
Myopathy ( )
Non-small-cell lung cancer ( )
Renal cell carcinoma ( )
Thyroid gland papillary carcinoma ( )
Thyroid tumor ( )
Adult lymphoma ( )
Congenital fiber-type disproportion myopathy ( )
Lymphoma ( )
Pediatric lymphoma ( )
Cap myopathy ( )
Childhood-onset nemaline myopathy ( )
Congenital generalized hypercontractile muscle stiffness syndrome ( )
Intermediate nemaline myopathy ( )
Undifferentiated carcinoma ( )
Colon cancer ( )
Congenital myopathy ( )
Neoplasm ( )
Neuroblastoma ( )
Pancreatic cancer ( )
Thyroid gland carcinoma ( )
UniProt ID
TPM3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6OTN
Pfam ID
PF00261
Sequence
MMEAIKKKMQMLKLDKENALDRAEQAEAEQKQAEERSKQLEDELAAMQKKLKGTEDELDK
YSEALKDAQEKLELAEKKAADAEAEVASLNRRIQLVEEELDRAQERLATALQKLEEAEKA
ADESERGMKVIENRALKDEEKMELQEIQLKEAKHIAEEADRKYEEVARKLVIIEGDLERT
EERAELAESKCSELEEELKNVTNNLKSLEAQAEKYSQKEDKYEEEIKILTDKLKEAETRA
EFAERSVAKLEKTIDDLEDELYAQKLKYKAISEELDHALNDMTSI
Function
Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.
KEGG Pathway
Cardiac muscle contraction (hsa04260 )
Adrenergic sig.ling in cardiomyocytes (hsa04261 )
Motor proteins (hsa04814 )
Cytoskeleton in muscle cells (hsa04820 )
Pathways in cancer (hsa05200 )
Thyroid cancer (hsa05216 )
Hypertrophic cardiomyopathy (hsa05410 )
Dilated cardiomyopathy (hsa05414 )
Reactome Pathway
Smooth Muscle Contraction (R-HSA-445355 )
RHOV GTPase cycle (R-HSA-9013424 )
Signaling by ALK fusions and activated point mutants (R-HSA-9725370 )
Striated Muscle Contraction (R-HSA-390522 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glioblastoma multiforme DISK8246 Definitive Biomarker [1]
Thyroid cancer DIS3VLDH Definitive Biomarker [2]
TPM3-related myopathy DIS1FW68 Definitive Semidominant [3]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [4]
Adenocarcinoma DIS3IHTY Strong Biomarker [5]
Adult glioblastoma DISVP4LU Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Anaplastic large cell lymphoma DISP4D1R Strong Altered Expression [7]
Autoimmune disease DISORMTM Strong Altered Expression [8]
Brain neoplasm DISY3EKS Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Altered Expression [11]
Carcinoma DISH9F1N Strong Biomarker [5]
Clear cell renal carcinoma DISBXRFJ Strong Genetic Variation [12]
Colon carcinoma DISJYKUO Strong Genetic Variation [13]
Colonic neoplasm DISSZ04P Strong Biomarker [14]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [15]
Congenital myopathy 4A, autosomal dominant DISU53TI Strong Autosomal dominant [16]
Congenital myopathy 4B, autosomal recessive DISPZ21Z Strong Autosomal recessive [17]
Gastric cancer DISXGOUK Strong Biomarker [18]
Gastric neoplasm DISOKN4Y Strong Biomarker [18]
Glioma DIS5RPEH Strong Biomarker [19]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [20]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Strong Biomarker [18]
Leukemia DISNAKFL Strong Biomarker [21]
Lung cancer DISCM4YA Strong Biomarker [9]
Mammary analogue secretory carcinoma DISGXZ2Q Strong Biomarker [5]
Melanoma DIS1RRCY Strong Biomarker [22]
Myopathy DISOWG27 Strong Biomarker [23]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [24]
Renal cell carcinoma DISQZ2X8 Strong Genetic Variation [12]
Thyroid gland papillary carcinoma DIS48YMM Strong Biomarker [25]
Thyroid tumor DISLVKMD Strong Biomarker [2]
Adult lymphoma DISK8IZR moderate Biomarker [26]
Congenital fiber-type disproportion myopathy DISU9T2M Moderate Semidominant [27]
Lymphoma DISN6V4S moderate Biomarker [26]
Pediatric lymphoma DIS51BK2 moderate Biomarker [26]
Cap myopathy DIS4S4WQ Supportive Autosomal dominant [28]
Childhood-onset nemaline myopathy DIST7MSL Supportive Autosomal dominant [29]
Congenital generalized hypercontractile muscle stiffness syndrome DISVT6KK Supportive Autosomal dominant [30]
Intermediate nemaline myopathy DISMJ4LI Supportive Autosomal dominant [31]
Undifferentiated carcinoma DISIAZST Disputed Biomarker [32]
Colon cancer DISVC52G Limited Genetic Variation [13]
Congenital myopathy DISLSK9G Limited Genetic Variation [33]
Neoplasm DISZKGEW Limited Biomarker [5]
Neuroblastoma DISVZBI4 Limited Biomarker [34]
Pancreatic cancer DISJC981 Limited Biomarker [35]
Thyroid gland carcinoma DISMNGZ0 Limited Biomarker [2]
------------------------------------------------------------------------------------
⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
PEITC DMOMN31 Phase 2 Tropomyosin alpha-3 chain (TPM3) affects the binding of PEITC. [55]
------------------------------------------------------------------------------------
21 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 Tropomyosin alpha-3 chain (TPM3). [36]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Tropomyosin alpha-3 chain (TPM3). [37]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tropomyosin alpha-3 chain (TPM3). [38]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Tropomyosin alpha-3 chain (TPM3). [39]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Tropomyosin alpha-3 chain (TPM3). [40]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Tropomyosin alpha-3 chain (TPM3). [41]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Tropomyosin alpha-3 chain (TPM3). [42]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Tropomyosin alpha-3 chain (TPM3). [44]
Decitabine DMQL8XJ Approved Decitabine decreases the expression of Tropomyosin alpha-3 chain (TPM3). [45]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Tropomyosin alpha-3 chain (TPM3). [14]
Benzatropine DMF7EXL Approved Benzatropine decreases the expression of Tropomyosin alpha-3 chain (TPM3). [47]
Sulfasalazine DMICA9H Approved Sulfasalazine decreases the expression of Tropomyosin alpha-3 chain (TPM3). [14]
Nabiximols DMHKJ5I Phase 3 Nabiximols decreases the expression of Tropomyosin alpha-3 chain (TPM3). [48]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Tropomyosin alpha-3 chain (TPM3). [41]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tropomyosin alpha-3 chain (TPM3). [50]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Tropomyosin alpha-3 chain (TPM3). [41]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Tropomyosin alpha-3 chain (TPM3). [45]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Tropomyosin alpha-3 chain (TPM3). [52]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of Tropomyosin alpha-3 chain (TPM3). [53]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of Tropomyosin alpha-3 chain (TPM3). [54]
Asacolitin DM3WVPJ Investigative Asacolitin decreases the expression of Tropomyosin alpha-3 chain (TPM3). [14]
------------------------------------------------------------------------------------
⏷ Show the Full List of 21 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Tropomyosin alpha-3 chain (TPM3). [43]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Tropomyosin alpha-3 chain (TPM3). [49]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Tropomyosin alpha-3 chain (TPM3). [51]
------------------------------------------------------------------------------------

References

1 EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy.Oncol Rep. 2014 Jan;31(1):480-7. doi: 10.3892/or.2013.2864. Epub 2013 Nov 20.
2 Targetable gene fusions identified in radioactive iodine refractory advanced thyroid carcinoma.Eur J Endocrinol. 2019 Apr 1;180(4):235-241. doi: 10.1530/EJE-18-0653.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 Oncogenic TRK fusions are amenable to inhibition in hematologic malignancies.J Clin Invest. 2018 Aug 31;128(9):3819-3825. doi: 10.1172/JCI120787. Epub 2018 Aug 6.
5 Immunohistochemistry with a pan-TRK antibody distinguishes secretory carcinoma of the salivary gland from acinic cell carcinoma.Histopathology. 2019 Jul;75(1):54-62. doi: 10.1111/his.13845. Epub 2019 May 16.
6 Resistance to TRK inhibition mediated by convergent MAPK pathway activation.Nat Med. 2019 Sep;25(9):1422-1427. doi: 10.1038/s41591-019-0542-z. Epub 2019 Aug 12.
7 Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma.Leuk Res. 2008 Mar;32(3):383-93. doi: 10.1016/j.leukres.2007.07.012. Epub 2007 Aug 27.
8 Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases.Genes Immun. 2013 Mar;14(2):67-82. doi: 10.1038/gene.2012.55. Epub 2012 Nov 29.
9 TRK inhibitors in TRK fusion-positive cancers.Ann Oncol. 2019 Nov 1;30(Suppl_8):viii23-viii30. doi: 10.1093/annonc/mdz282.
10 Delivery of platelet TPM3 mRNA into breast cancer cells via microvesicles enhances metastasis.FEBS Open Bio. 2019 Dec;9(12):2159-2169. doi: 10.1002/2211-5463.12759. Epub 2019 Nov 21.
11 Non-secretory breast carcinomas lack NTRK rearrangements and TRK protein expression.Pathol Int. 2019 Feb;69(2):94-96. doi: 10.1111/pin.12766. Epub 2019 Feb 1.
12 ALK-TPM3 rearrangement in adult renal cell carcinoma: a case report and literature review.Diagn Pathol. 2019 Oct 18;14(1):112. doi: 10.1186/s13000-019-0879-0.
13 NTRK1 fusions for the therapeutic intervention of Korean patients with colon cancer.Oncotarget. 2016 Feb 16;7(7):8399-412. doi: 10.18632/oncotarget.6724.
14 Mesalamine suppresses the expression of TC22, a novel tropomyosin isoform associated with colonic neoplasia. Mol Pharmacol. 2009 Jul;76(1):183-91. doi: 10.1124/mol.109.056028. Epub 2009 Apr 15.
15 Gel-Based Proteomics of Clinical Samples Identifies Potential Serological Biomarkers for Early Detection of Colorectal Cancer.Int J Mol Sci. 2019 Dec 2;20(23):6082. doi: 10.3390/ijms20236082.
16 Mutations in TPM3 are a common cause of congenital fiber type disproportion. Ann Neurol. 2008 Mar;63(3):329-37. doi: 10.1002/ana.21308.
17 Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy. Neuromuscul Disord. 1999 Dec;9(8):573-9. doi: 10.1016/s0960-8966(99)00053-x.
18 Diverse proteomic alterations in gastric adenocarcinoma.Proteomics. 2004 Oct;4(10):3276-87. doi: 10.1002/pmic.200300916.
19 Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma.Br J Cancer. 2018 Sep;119(6):693-696. doi: 10.1038/s41416-018-0251-2. Epub 2018 Sep 17.
20 Identification and characterization of tropomyosin 3 associated with granulin-epithelin precursor in human hepatocellular carcinoma.PLoS One. 2012;7(7):e40324. doi: 10.1371/journal.pone.0040324. Epub 2012 Jul 6.
21 Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia.Blood. 2010 May 20;115(20):4061-70. doi: 10.1182/blood-2008-06-163386. Epub 2010 Mar 11.
22 Decreased expression of a single tropomyosin isoform, TM5/TM30nm, results in reduction in motility of highly metastatic B16-F10 mouse melanoma cells.Biochem Biophys Res Commun. 1996 Aug 14;225(2):427-35. doi: 10.1006/bbrc.1996.1190.
23 1q21.3 deletion involving GATAD2B: An emerging recurrent microdeletion syndrome.Am J Med Genet A. 2017 Mar;173(3):766-770. doi: 10.1002/ajmg.a.38082.
24 Dual drive coexistence of EML4-ALK and TPM3-ROS1 fusion in advanced lung adenocarcinoma.Thorac Cancer. 2018 Feb;9(2):324-327. doi: 10.1111/1759-7714.12578. Epub 2017 Dec 18.
25 Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study.Lancet Oncol. 2018 May;19(5):705-714. doi: 10.1016/S1470-2045(18)30119-0. Epub 2018 Mar 29.
26 Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas.Leukemia. 2011 Dec;25(12):1882-90. doi: 10.1038/leu.2011.168. Epub 2011 Jul 22.
27 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
28 Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3. Neuromuscul Disord. 2010 Jul;20(7):464-6. doi: 10.1016/j.nmd.2010.05.012. Epub 2010 Jun 15.
29 A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. Nat Genet. 1995 Jan;9(1):75-9. doi: 10.1038/ng0195-75.
30 TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype. Ann Neurol. 2015 Dec;78(6):982-994. doi: 10.1002/ana.24535. Epub 2015 Nov 13.
31 Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin. Eur J Hum Genet. 2008 Sep;16(9):1055-61. doi: 10.1038/ejhg.2008.60. Epub 2008 Apr 2.
32 Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
33 Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies.Hum Mutat. 2014 Jul;35(7):779-90. doi: 10.1002/humu.22554. Epub 2014 May 1.
34 Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma.Drug Des Devel Ther. 2018 Oct 23;12:3549-3561. doi: 10.2147/DDDT.S147384. eCollection 2018.
35 Research on the establishment of a TPM3 monoclonal stable transfected PANC-1 cell line and the experiment of the EMT occurrence in human pancreatic cancer.Onco Targets Ther. 2019 Jul 11;12:5577-5587. doi: 10.2147/OTT.S212689. eCollection 2019.
36 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
37 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
38 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.
39 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
40 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.
41 Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
42 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.
43 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
44 Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
45 Synergistic effect of trichostatin A and 5-aza-2'-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: a proteomic study. Proteomics. 2009 Apr;9(7):1952-66. doi: 10.1002/pmic.200701089.
46 Mesalamine suppresses the expression of TC22, a novel tropomyosin isoform associated with colonic neoplasia. Mol Pharmacol. 2009 Jul;76(1):183-91. doi: 10.1124/mol.109.056028. Epub 2009 Apr 15.
47 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
48 Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
49 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.
50 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.
51 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
52 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
53 Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
54 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
55 Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.