Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFYAWE5)

• DOT Name: Developmentally-regulated GTP-binding protein 2 (DRG2)
• Synonyms: DRG-2; Translation factor GTPase DRG2; TRAFAC GTPase DRG2; EC 3.6.5.-
• Gene Name: DRG2
• Related Disease:
  Hepatocellular carcinoma
  Melanoma
  Neoplasm
• UniProt ID: DRG2_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF01926 ; PF16897 ; PF02824
• Sequence:
  MGILEKISEIEKEIARTQKNKATEYHLGLLKAKLAKYRAQLLEPSKSASSKGEGFDVMKS
  GDARVALIGFPSVGKSTFLSLMTSTASEAASYEFTTLTCIPGVIEYKGANIQLLDLPGII
  EGAAQGKGRGRQVIAVARTADVIIMMLDATKGEVQRSLLEKELESVGIRLNKHKPNIYFK
  PKKGGGISFNSTVTLTQCSEKLVQLILHEYKIFNAEVLFREDCSPDEFIDVIVGNRVYMP
  CLYVYNKIDQISMEEVDRLARKPNSVVISCGMKLNLDYLLEMLWEYLALTCIYTKKRGQR
  PDFTDAIILRKGASVEHVCHRIHRSLASQFKYALVWGTSTKYSPQRVGLTHTMEHEDVIQ
  IVKK
• Function: Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP. When hydroxylated at C-3 of 'Lys-21' by JMJD7, may bind to RNA and play a role in translation.
• Tissue Specificity: Highest levels in skeletal muscle, heart and kidney. Low levels in colon, thymus, spleen, small intestine, lung and Leukocytes.
• Reactome Pathway: Protein hydroxylation (R-HSA-9629569)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Melanoma	DIS1RRCY	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[5]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Developmentally-regulated GTP-binding protein 2 (DRG2).	[11]

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 decreases the methylation of Developmentally-regulated GTP-binding protein 2 (DRG2).	[10]

References

• [1] Efficacy of early treatment on 52 patients with preneoplastic hepatitis B virus-associated hepatocellular carcinoma by compound Phyllanthus Urinaria L.Chin J Integr Med. 2014 Apr;20(4):263-71. doi: 10.1007/s11655-013-1320-7. Epub 2013 Mar 25.
• [2] DRG2 supports the growth of primary tumors and metastases of melanoma by enhancing VEGF-A expression.FEBS J. 2020 May;287(10):2070-2086. doi: 10.1111/febs.15125. Epub 2019 Dec 1.
• [3] Functional intronic variant of SLC5A10 affects DRG2 expression and survival outcomes of early-stage non-small-cell lung cancer.Cancer Sci. 2018 Dec;109(12):3902-3909. doi: 10.1111/cas.13814. Epub 2018 Nov 7.
• [4] 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.
• [5] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [6] 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.
• [7] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [8] 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.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] 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.
• [11] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.