Details of Drug Off-Target (DOT)

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

• DOT Name: Ras-related protein Rab-22A (RAB22A)
• Synonyms: Rab-22
• Gene Name: RAB22A
• UniProt ID: RB22A_HUMAN
• Pfam ID: PF00071
• Sequence:
  MALRELKVCLLGDTGVGKSSIVWRFVEDSFDPNINPTIGASFMTKTVQYQNELHKFLIWD
  TAGQERFRALAPMYYRGSAAAIIVYDITKEETFSTLKNWVKELRQHGPPNIVVAIAGNKC
  DLIDVREVMERDAKDYADSIHAIFVETSAKNAININELFIEISRRIPSTDANLPSGGKGF
  KLRRQPSEPKRSCC
• Function: Plays a role in endocytosis and intracellular protein transport. Mediates trafficking of TF from early endosomes to recycling endosomes. Required for NGF-mediated endocytosis of NTRK1, and subsequent neurite outgrowth. Binds GTP and GDP and has low GTPase activity. Alternates between a GTP-bound active form and a GDP-bound inactive form.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

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 Ras-related protein Rab-22A (RAB22A).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ras-related protein Rab-22A (RAB22A).	[9]

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-22A (RAB22A).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-related protein Rab-22A (RAB22A).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ras-related protein Rab-22A (RAB22A).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ras-related protein Rab-22A (RAB22A).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ras-related protein Rab-22A (RAB22A).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ras-related protein Rab-22A (RAB22A).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-related protein Rab-22A (RAB22A).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-related protein Rab-22A (RAB22A).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ras-related protein Rab-22A (RAB22A).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ras-related protein Rab-22A (RAB22A).	[12]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Ras-related protein Rab-22A (RAB22A).	[13]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.