Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07JK0M)

• DOT Name: Rho GDP-dissociation inhibitor 3 (ARHGDIG)
• Synonyms: Rho GDI 3; Rho-GDI gamma
• Gene Name: ARHGDIG
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: GDIR3_HUMAN
• Pfam ID: PF02115
• Sequence:
  MLGLDACELGAQLLELLRLALCARVLLADKEGGPPAVDEVLDEAVPEYRAPGRKSLLEIR
  QLDPDDRSLAKYKRVLLGPLPPAVDPSLPNVQVTRLTLLSEQAPGPVVMDLTGDLAVLKD
  QVFVLKEGVDYRVKISFKVHREIVSGLKCLHHTYRRGLRVDKTVYMVGSYGPSAQEYEFV
  TPVEEAPRGALVRGPYLVVSLFTDDDRTHHLSWEWGLCICQDWKD
• Function: Inhibits GDP/GTP exchange reaction of RhoB. Interacts specifically with the GDP- and GTP-bound forms of post-translationally processed Rhob and Rhog proteins, both of which show a growth-regulated expression in mammalian cells. Stimulates the release of the GDP-bound but not the GTP-bound RhoB protein. Also inhibits the GDP/GTP exchange of RhoB but shows less ability to inhibit the dissociation of prebound GTP.
• Tissue Specificity: Primarily expressed in pancreas and brain.
• KEGG Pathway:
  Neurotrophin sig.ling pathway (hsa04722)
  Vasopressin-regulated water reabsorption (hsa04962)
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOB GTPase cycle (R-HSA-9013026)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]

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 Rho GDP-dissociation inhibitor 3 (ARHGDIG).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rho GDP-dissociation inhibitor 3 (ARHGDIG).	[5]

5 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 Rho GDP-dissociation inhibitor 3 (ARHGDIG).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rho GDP-dissociation inhibitor 3 (ARHGDIG).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rho GDP-dissociation inhibitor 3 (ARHGDIG).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rho GDP-dissociation inhibitor 3 (ARHGDIG).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Rho GDP-dissociation inhibitor 3 (ARHGDIG).	[8]

References

• [1] Prognostic value of rho GTPases and rho guanine nucleotide dissociation inhibitors in human breast cancers.Clin Cancer Res. 2003 Dec 15;9(17):6432-40.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.