Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07F6PE)

• DOT Name: GTP-binding protein Di-Ras1 (DIRAS1)
• Synonyms: Distinct subgroup of the Ras family member 1; Ras-related inhibitor of cell growth; Rig; Small GTP-binding tumor suppressor 1
• Gene Name: DIRAS1
• Related Disease:
  Anemia
  Esophageal squamous cell carcinoma
  Leukopenia
  Neoplasm
  Clear cell renal carcinoma
  Renal cell carcinoma
  Adult glioblastoma
  Astrocytoma
  Glioblastoma multiforme
  Glioma
• UniProt ID: DIRA1_HUMAN
• PDB ID: 2GF0
• Pfam ID: PF00071
• Sequence:
  MPEQSNDYRVVVFGAGGVGKSSLVLRFVKGTFRDTYIPTIEDTYRQVISCDKSVCTLQIT
  DTTGSHQFPAMQRLSISKGHAFILVFSVTSKQSLEELGPIYKLIVQIKGSVEDIPVMLVG
  NKCDETQREVDTREAQAVAQEWKCAFMETSAKMNYNVKELFQELLTLETRRNMSLNIDGK
  RSGKQKRTDRVKGKCTLM
• Function: Displays low GTPase activity and exists predominantly in the GTP-bound form.
• Tissue Specificity: Highly expressed in heart and brain.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anemia	DISTVL0C	Strong	Genetic Variation	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[2]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[3]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[4]
Astrocytoma	DISL3V18	Limited	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[4]
Glioma	DIS5RPEH	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of GTP-binding protein Di-Ras1 (DIRAS1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of GTP-binding protein Di-Ras1 (DIRAS1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GTP-binding protein Di-Ras1 (DIRAS1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of GTP-binding protein Di-Ras1 (DIRAS1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of GTP-binding protein Di-Ras1 (DIRAS1).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of GTP-binding protein Di-Ras1 (DIRAS1).	[10]

References

• [1] A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer.Ann Oncol. 2015 Sep;26(9):1923-1929. doi: 10.1093/annonc/mdv264. Epub 2015 Jun 19.
• [2] Downregulation of the novel tumor suppressor DIRAS1 predicts poor prognosis in esophageal squamous cell carcinoma.Cancer Res. 2013 Apr 1;73(7):2298-309. doi: 10.1158/0008-5472.CAN-12-2663. Epub 2013 Feb 22.
• [3] RNAa and Vector-Mediated Overexpression of DIRAS1 Suppresses Tumor Growth and Migration in Renal Cell Carcinoma.Mol Ther Nucleic Acids. 2018 Sep 7;12:845-853. doi: 10.1016/j.omtn.2018.07.019. Epub 2018 Aug 8.
• [4] Identification of a novel gene product, RIG, that is down-regulated in human glioblastoma.Oncogene. 1997 Mar 6;14(9):1075-81. doi: 10.1038/sj.onc.1200925.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] 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.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.