Details of Drug Off-Target (DOT)

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

• DOT Name: Large ribosomal subunit protein mL62 (MRPL58)
• Synonyms: 39S ribosomal protein L58, mitochondrial; MRP-L58; Digestion substraction 1; DS-1; Immature colon carcinoma transcript 1 protein; Peptidyl-tRNA hydrolase ICT1, mitochondrial; EC 3.1.1.29
• Gene Name: MRPL58
• Related Disease:
  B-cell lymphoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Gastric cancer
  Hepatocellular carcinoma
  Neoplasm
  Stomach cancer
  Breast cancer
  Breast carcinoma
  leukaemia
  Leukemia
• UniProt ID: ICT1_HUMAN
• PDB ID: 3J7Y ; 3J9M ; 5OOL ; 5OOM ; 6I9R ; 6NU2 ; 6NU3 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5H ; 7A5I ; 7A5J ; 7A5K ; 7L08 ; 7L20 ; 7NQL ; 7O9K ; 7O9M ; 7ODR ; 7ODS ; 7ODT ; 7OF0 ; 7OF2 ; 7OF3 ; 7OF4 ; 7OF5 ; 7OF6 ; 7OF7 ; 7OG4 ; 7OI6 ; 7OI7 ; 7OI8 ; 7OI9 ; 7OIA ; 7OIB ; 7OIC ; 7OID ; 7OIE ; 7PD3 ; 7PO4 ; 7QH6 ; 7QH7 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8OIR ; 8OIT
• EC Number: 3.1.1.29
• Pfam ID: PF00472
• Sequence:
  MAATRCLRWGLSRAGVWLLPPPARCPRRALHKQKDGTEFKSIYSLDKLYPESQGSDTAWR
  VPNGAKQADSDIPLDRLTISYCRSSGPGGQNVNKVNSKAEVRFHLATAEWIAEPVRQKIA
  ITHKNKINRLGELILTSESSRYQFRNLADCLQKIRDMITEASQTPKEPTKEDVKLHRIRI
  ENMNRERLRQKRIHSAVKTSRRVDMD
• Function: Essential peptidyl-tRNA hydrolase component of the mitochondrial large ribosomal subunit. Acts as a codon-independent translation release factor that has lost all stop codon specificity and directs the termination of translation in mitochondrion, possibly in case of abortive elongation. Involved in the hydrolysis of peptidyl-tRNAs that have been prematurely terminated and thus in the recycling of stalled mitochondrial ribosomes.
• Tissue Specificity: Down-regulated during the in vitro differentiation of HT29-D4 colon carcinoma cells.
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[6]
Neoplasm	DISZKGEW	moderate	Altered Expression	[6]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[5]
Breast cancer	DIS7DPX1	Limited	Biomarker	[7]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[7]
leukaemia	DISS7D1V	Limited	Biomarker	[3]
Leukemia	DISNAKFL	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Large ribosomal subunit protein mL62 (MRPL58).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein mL62 (MRPL58).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein mL62 (MRPL58).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Large ribosomal subunit protein mL62 (MRPL58).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Large ribosomal subunit protein mL62 (MRPL58).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein mL62 (MRPL58).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Large ribosomal subunit protein mL62 (MRPL58).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Large ribosomal subunit protein mL62 (MRPL58).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Large ribosomal subunit protein mL62 (MRPL58).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the methylation of Large ribosomal subunit protein mL62 (MRPL58).	[17]

References

• [1] ICT1 predicts a poor survival and correlated with cell proliferation in diffuse large B-cell lymphoma.Gene. 2017 Sep 5;627:255-262. doi: 10.1016/j.gene.2017.06.028. Epub 2017 Jun 16.
• [2] Immature Colon Carcinoma Transcript-1 (ICT1) Expression Correlates with Unfavorable Prognosis and Survival in Patients with Colorectal Cancer.Ann Surg Oncol. 2016 Nov;23(12):3924-3933. doi: 10.1245/s10434-016-5305-1. Epub 2016 Jul 13.
• [3] Knockdown of immature colon carcinoma transcript1 induces suppression of proliferation, S-phase arrest and apoptosis in leukemia cells.Oncol Rep. 2018 Mar;39(3):1269-1275. doi: 10.3892/or.2018.6185. Epub 2018 Jan 3.
• [4] Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non-Small Cell Lung Cancer Cells.Technol Cancer Res Treat. 2017 Oct;16(5):559-569. doi: 10.1177/1533034616657977. Epub 2016 Jul 13.
• [5] miR-205 regulation of ICT1 has an oncogenic potential via promoting the migration and invasion of gastric cancer cells.Biomed Pharmacother. 2017 Dec;96:191-197. doi: 10.1016/j.biopha.2017.09.147. Epub 2017 Oct 6.
• [6] Immature colon carcinoma transcript-1 promotes cell growth of hepatocellular carcinoma via facilitating cell cycle progression and apoptosis resistance.Oncol Rep. 2017 Dec;38(6):3489-3496. doi: 10.3892/or.2017.6046. Epub 2017 Oct 19.
• [7] MiR-1301-3p inhibits human breast cancer cell proliferation by regulating cell cycle progression and apoptosis through directly targeting ICT1.Breast Cancer. 2018 Nov;25(6):742-752. doi: 10.1007/s12282-018-0881-5. Epub 2018 Jun 27.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [17] DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.