Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO9VJS9)

• DOT Name: Ras-related protein Rab-9A (RAB9A)
• Gene Name: RAB9A
• UniProt ID: RAB9A_HUMAN
• PDB ID: 1WMS; 7E1T
• Pfam ID: PF00071
• Sequence:
  MAGKSSLFKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTMQI
  WDTAGQERFRSLRTPFYRGSDCCLLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFV
  ILGNKIDISERQVSTEEAQAWCRDNGDYPYFETSAKDATNVAAAFEEAVRRVLATEDRSD
  HLIQTDTVNLHRKPKPSSSCC
• Function: Involved in the transport of proteins between the endosomes and the trans Golgi network. Involved in the recruitment of SGSM2 to melanosomes and is required for the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes.
• KEGG Pathway:
  Salmonella infection (hsa05132)
  Measles (hsa05162)
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  RHOBTB3 ATPase cycle (R-HSA-9706019)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Rab-9A (RAB9A).	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-9A (RAB9A).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ras-related protein Rab-9A (RAB9A).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ras-related protein Rab-9A (RAB9A).	[4]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Ras-related protein Rab-9A (RAB9A).	[5]
Phenol	DM1QSM3	Phase 2/3	Phenol decreases the expression of Ras-related protein Rab-9A (RAB9A).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Ras-related protein Rab-9A (RAB9A).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ras-related protein Rab-9A (RAB9A).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-related protein Rab-9A (RAB9A).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ras-related protein Rab-9A (RAB9A).	[12]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Ras-related protein Rab-9A (RAB9A).	[6]

3 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 increases the methylation of Ras-related protein Rab-9A (RAB9A).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ras-related protein Rab-9A (RAB9A).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ras-related protein Rab-9A (RAB9A).	[10]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [2] 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.
• [3] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [4] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [5] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [6] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [7] 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.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.