Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIFYMI3)

• DOT Name: Developmentally-regulated GTP-binding protein 1 (DRG1)
• Synonyms: DRG-1; Neural precursor cell expressed developmentally down-regulated protein 3; NEDD-3; Translation factor GTPase DRG1; TRAFAC GTPase DRG1; EC 3.6.5.-
• Gene Name: DRG1
• Related Disease:
  Advanced cancer
  Diabetic kidney disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Esophageal squamous cell carcinoma
  Immunodeficiency
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Urinary bladder neoplasm
  Melanoma
  Complex neurodevelopmental disorder
  Neoplasm
• UniProt ID: DRG1_HUMAN
• PDB ID: 2EKI
• EC Number: 3.6.5.-
• Pfam ID: PF01926 ; PF16897 ; PF02824
• Sequence:
  MSSTLAKIAEIEAEMARTQKNKATAHHLGLLKARLAKLRRELITPKGGGGGGPGEGFDVA
  KTGDARIGFVGFPSVGKSTLLSNLAGVYSEVAAYEFTTLTTVPGVIRYKGAKIQLLDLPG
  IIEGAKDGKGRGRQVIAVARTCNLILIVLDVLKPLGHKKIIENELEGFGIRLNSKPPNIG
  FKKKDKGGINLTATCPQSELDAETVKSILAEYKIHNADVTLRSDATADDLIDVVEGNRVY
  IPCIYVLNKIDQISIEELDIIYKVPHCVPISAHHRWNFDDLLEKIWDYLKLVRIYTKPKG
  QLPDYTSPVVLPYSRTTVEDFCMKIHKNLIKEFKYALVWGLSVKHNPQKVGKDHTLEDED
  VIQIVKK
• Function: Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP. Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions. When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation. Binds to microtubules and promotes microtubule polymerization and stability that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions.
• Tissue Specificity: High levels in skeletal muscle, heart, and kidney. Intermediate levels in liver, placenta and brain. 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

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Diabetic kidney disease	DISJMWEY	Definitive	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[5]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Immunodeficiency	DIS093I0	Strong	Biomarker	[6]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[10]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[12]
Melanoma	DIS1RRCY	moderate	Biomarker	[13]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[14]
Neoplasm	DISZKGEW	Limited	Altered Expression	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Developmentally-regulated GTP-binding protein 1 (DRG1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Developmentally-regulated GTP-binding protein 1 (DRG1).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Developmentally-regulated GTP-binding protein 1 (DRG1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Developmentally-regulated GTP-binding protein 1 (DRG1).	[19]

References

• [1] Metastasis suppressors in human benign prostate, intraepithelial neoplasia, and invasive cancer: their prospects as therapeutic agents.Med Res Rev. 2012 Sep;32(5):1026-77. doi: 10.1002/med.20232. Epub 2011 Jan 16.
• [2] A genome-wide association study for diabetic nephropathy genes in African Americans.Kidney Int. 2011 Mar;79(5):563-72. doi: 10.1038/ki.2010.467. Epub 2010 Dec 8.
• [3] Preclinical studies of molecular-targeting diagnostic and therapeutic strategies against breast cancer.Breast Cancer. 2008;15(1):73-8. doi: 10.1007/s12282-007-0015-y.
• [4] Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression.Oncogene. 2004 Jul 22;23(33):5675-81. doi: 10.1038/sj.onc.1207734.
• [5] Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas.Oncotarget. 2017 Oct 9;8(58):98623-98634. doi: 10.18632/oncotarget.21697. eCollection 2017 Nov 17.
• [6] The tumor metastasis suppressor gene Drg-1 down-regulates the expression of activating transcription factor 3 in prostate cancer.Cancer Res. 2006 Dec 15;66(24):11983-90. doi: 10.1158/0008-5472.CAN-06-0943.
• [7] Oncogenic but non-essential role of N-myc downstream regulated gene 1 in the progression of esophageal squamous cell carcinoma.Cancer Biol Ther. 2013 Feb;14(2):164-74. doi: 10.4161/cbt.22956. Epub 2012 Nov 28.
• [8] DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation.Oncotarget. 2016 Nov 8;7(45):72795-72806. doi: 10.18632/oncotarget.11973.
• [9] NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer.J Thorac Oncol. 2012 May;7(5):779-89. doi: 10.1097/JTO.0b013e31824c92b4.
• [10] Differentiation-related gene-1 decreases Bim stability by proteasome-mediated degradation.Cancer Res. 2009 Aug 1;69(15):6115-21. doi: 10.1158/0008-5472.CAN-08-3024. Epub 2009 Jul 21.
• [11] The Drg-1 gene suppresses tumor metastasis in prostate cancer.Cancer Res. 2003 Apr 15;63(8):1731-6.
• [12] Analysis of the expression of biomarkers in urinary bladder cancer using a tissue microarray.Mol Carcinog. 2008 Sep;47(9):678-85. doi: 10.1002/mc.20420.
• [13] Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.PLoS One. 2015 May 20;10(5):e0124094. doi: 10.1371/journal.pone.0124094. eCollection 2015.
• [14] 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.
• [15] Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors. Mol Cancer Ther. 2005 May;4(5):843-54.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] 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.
• [18] 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.
• [19] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.