Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYW7ED8)

• DOT Name: Rho GTPase-activating protein 25 (ARHGAP25)
• Synonyms: Rho-type GTPase-activating protein 25
• Gene Name: ARHGAP25
• Related Disease:
  Type-1 diabetes
  Lung cancer
  Lung carcinoma
  Colorectal carcinoma
• UniProt ID: RHG25_HUMAN
• PDB ID: 1V89
• Pfam ID: PF00169 ; PF00620
• Sequence:
  MSLKLPRNWDFNLKVEAAKIARSRSVMTGEQMAAFHPSSTPNPLERPIKMGWLKKQRSIV
  KNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPASWD
  QNRMGQDSYVLMASSQAEMEEWVKFLRRVAGTPCGVFGQRLDETVAYEQKFGPHLVPILV
  EKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLR
  DLPEPVVPWSQYEGFLLCGQLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQL
  NCAVNKMSVDNLATVIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMIRDHEVLFPKSKDIP
  LSPPAQKNDPKKAPVARSSVGWDATEDLRISRTDSFSSMTSDSDTTSPTGQQPSDAFPED
  SSKVPREKPGDWKMQSRKRTQTLPNRKCFLTSAFQGANSSKMEIFKNEFWSPSSEAKAGE
  GHRRTMSQDLRQLSDSQRTSTYDNVPSLPGSPGEEASALSSQACDSKGDTLASPNSETGP
  GKKNSGEEEIDSLQRMVQELRKEIETQKQMYEEQIKNLEKENYDVWAKVVRLNEELEKEK
  KKSAALEISLRNMERSREDVEKRNKALEEEVKEFVKSMKEPKTEA
• Function: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
• Reactome Pathway: RAC1 GTPase cycle (R-HSA-9013149)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rho GTPase-activating protein 25 (ARHGAP25).	[4]

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 Rho GTPase-activating protein 25 (ARHGAP25).	[5]

References

• [1] Comparative analysis of gene expression profiles in children with type 1 diabetes mellitus.Mol Med Rep. 2019 May;19(5):3989-4000. doi: 10.3892/mmr.2019.10099. Epub 2019 Mar 28.
• [2] The tumor suppressive roles of ARHGAP25 in lung cancer cells.Onco Targets Ther. 2019 Aug 19;12:6699-6710. doi: 10.2147/OTT.S207540. eCollection 2019.
• [3] Weichang'an suppressed migration and invasion of HCT116 cells by inhibiting Wnt/-catenin pathway while upregulating ARHGAP25.Biotechnol Appl Biochem. 2019 Sep;66(5):787-793. doi: 10.1002/bab.1784. Epub 2019 Aug 19.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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.