Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXLGJ4R)

• DOT Name: Tropomodulin-4 (TMOD4)
• Synonyms: Skeletal muscle tropomodulin; Sk-Tmod
• Gene Name: TMOD4
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Glioma
  Myocardial infarction
  Neoplasm
  Precancerous condition
  Small lymphocytic lymphoma
  Tarsal-carpal coalition syndrome
  Breast cancer
  Breast carcinoma
  Advanced cancer
  Gastric cancer
  Hepatocellular carcinoma
  Stomach cancer
• UniProt ID: TMOD4_HUMAN
• Pfam ID: PF03250
• Sequence:
  MSSYQKELEKYRDIDEDEILRTLSPEELEQLDCELQEMDPENMLLPAGLRQRDQTKKSPT
  GPLDREALLQYLEQQALEVKERDDLVPFTGEKKGKPYIQPKREIPAEEQITLEPELEEAL
  AHATDAEMCDIAAILDMYTLMSNKQYYDALCSGEICNTEGISSVVQPDKYKPVPDEPPNP
  TNIEEILKRVRSNDKELEEVNLNNIQDIPIPMLSELCEAMKANTYVRSFSLVATRSGDPI
  ANAVADMLRENRSLQSLNIESNFISSTGLMAVLKAVRENATLTELRVDNQRQWPGDAVEM
  EMATVLEQCPSIVRFGYHFTQQGPRARAAQAMTRNNELRRQQKKR
• 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: Highly expressed in skeletal muscle.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Precancerous condition	DISV06FL	Strong	Altered Expression	[5]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[6]
Tarsal-carpal coalition syndrome	DISY90L2	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	moderate	Biomarker	[8]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[9]
Gastric cancer	DISXGOUK	Limited	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tropomodulin-4 (TMOD4).	[11]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Tropomodulin-4 (TMOD4).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tropomodulin-4 (TMOD4).	[14]

1 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 Tropomodulin-4 (TMOD4).	[13]

References

• [1] Gelsolin-like actin-capping proteinis associated with patient prognosis, cellular apoptosis and proliferation in prostate cancer.Biomark Med. 2016 Dec;10(12):1251-1260. doi: 10.2217/bmm-2016-0186. Epub 2016 Dec 7.
• [2] Actin-capping protein CapG is associated with prognosis, proliferation and metastasis in human glioma.Oncol Rep. 2018 Mar;39(3):1011-1022. doi: 10.3892/or.2018.6225. Epub 2018 Jan 22.
• [3] Identification of 13 novel susceptibility loci for early-onset myocardial infarction, hypertension, or chronic kidney disease.Int J Mol Med. 2018 Nov;42(5):2415-2436. doi: 10.3892/ijmm.2018.3852. Epub 2018 Sep 4.
• [4] Gelsolin-like Actin-capping Protein (CapG) Overexpression in the Cytoplasm of Human Hepatocellular Carcinoma, Associated with Cellular Invasion, Migration and Tumor Prognosis.Anticancer Res. 2018 Jul;38(7):3943-3950. doi: 10.21873/anticanres.12680.
• [5] Clinical significance of gelsolin-like actin-capping protein expression in oral carcinogenesis: an immunohistochemical study of premalignant and malignant lesions of the oral cavity.BMC Cancer. 2008 Feb 1;8:39. doi: 10.1186/1471-2407-8-39.
• [6] Proteomic analysis of chronic lymphocytic leukemia subtypes with mutated or unmutated Ig V(H) genes.Mol Cell Proteomics. 2003 Dec;2(12):1331-41. doi: 10.1074/mcp.M300055-MCP200. Epub 2003 Oct 13.
• [7] Gelsolin-like actin-capping protein has prognostic value and promotes tumorigenesis and epithelial-mesenchymal transition via the Hippo signaling pathway in human bladder cancer.Ther Adv Med Oncol. 2019 Apr 29;11:1758835919841235. doi: 10.1177/1758835919841235. eCollection 2019.
• [8] A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis.Breast Cancer Res. 2013 Dec 13;15(6):R116. doi: 10.1186/bcr3585.
• [9] Prognostic and clinicopathological significance of CapG in various cancers: Evidence from a meta-analysis.Pathol Res Pract. 2019 Dec;215(12):152683. doi: 10.1016/j.prp.2019.152683. Epub 2019 Oct 12.
• [10] Prognostic value of CAPZA1 overexpression in gastric cancer.Int J Oncol. 2013 May;42(5):1569-77. doi: 10.3892/ijo.2013.1867. Epub 2013 Mar 27.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [13] 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.
• [14] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.