Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHHU6WA)

• DOT Name: Ras-related protein Rab-33A (RAB33A)
• Synonyms: Small GTP-binding protein S10
• Gene Name: RAB33A
• Related Disease:
  Signet ring cell carcinoma
  Tuberculosis
• UniProt ID: RB33A_HUMAN
• Pfam ID: PF00071
• Sequence:
  MAQPILGHGSLQPASAAGLASLELDSSLDQYVQIRIFKIIVIGDSNVGKTCLTFRFCGGT
  FPDKTEATIGVDFREKTVEIEGEKIKVQVWDTAGQERFRKSMVEHYYRNVHAVVFVYDVT
  KMTSFTNLKMWIQECNGHAVPPLVPKVLVGNKCDLREQIQVPSNLALKFADAHNMLLFET
  SAKDPKESQNVESIFMCLACRLKAQKSLLYRDAERQQGKVQKLEFPQEANSKTSCPC
• Tissue Specificity: Expressed only in lymphoid cell lines.
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  TBC/RABGAPs (R-HSA-8854214)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Signet ring cell carcinoma	DISVCUCR	Strong	Biomarker	[1]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ras-related protein Rab-33A (RAB33A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-related protein Rab-33A (RAB33A).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ras-related protein Rab-33A (RAB33A).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ras-related protein Rab-33A (RAB33A).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ras-related protein Rab-33A (RAB33A).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Ras-related protein Rab-33A (RAB33A).	[8]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Ras-related protein Rab-33A (RAB33A).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ras-related protein Rab-33A (RAB33A).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-related protein Rab-33A (RAB33A).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-related protein Rab-33A (RAB33A).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-related protein Rab-33A (RAB33A).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ras-related protein Rab-33A (RAB33A).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ras-related protein Rab-33A (RAB33A).	[14]

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 Ras-related protein Rab-33A (RAB33A).	[10]

References

• [1] Expression of DNMTs and genomic DNA methylation in gastric signet ring cell carcinoma.Mol Med Rep. 2013 Sep;8(3):942-8. doi: 10.3892/mmr.2013.1566. Epub 2013 Jul 2.
• [2] Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India.Genes Immun. 2013 Sep;14(6):356-64. doi: 10.1038/gene.2013.26. Epub 2013 May 16.
• [3] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [10] 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.
• [11] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [12] 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.
• [13] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.