Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP9OOVS)

• DOT Name: Ras-related protein Rab-20 (RAB20)
• Gene Name: RAB20
• Related Disease:
  Tuberculosis
  Adenoma
  Advanced cancer
  Carcinoma
  Hypothyroidism
  Adenocarcinoma
  Pancreatic cancer
  Acute myelogenous leukaemia
  Bacterial infection
• UniProt ID: RAB20_HUMAN
• Pfam ID: PF00071
• Sequence:
  MRKPDSKIVLLGDMNVGKTSLLQRYMERRFPDTVSTVGGAFYLKQWRSYNISIWDTAGRE
  QFHGLGSMYCRGAAAIILTYDVNHRQSLVELEDRFLGLTDTASKDCLFAIVGNKVDLTEE
  GALAGQEKEECSPNMDAGDRVSPRAPKQVQLEDAVALYKKILKYKMLDEQDVPAAEQMCF
  ETSAKTGYNVDLLFETLFDLVVPMILQQRAERPSHTVDISSHKPPKRTRSGCCA
• Function: Plays a role in apical endocytosis/recycling. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in the fusion of phagosomes with lysosomes.
• Tissue Specificity: Low or absent expression in normal pancreas and stronger expression in 15 of 18 exocrine pancreatic adenocarcinomas (at protein level).
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tuberculosis	DIS2YIMD	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[4]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[5]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[5]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[6]
Bacterial infection	DIS5QJ9S	Limited	Altered Expression	[7]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Ras-related protein Rab-20 (RAB20) affects the response to substance of Fluorouracil.	[24]
Etoposide	DMNH3PG	Approved	Ras-related protein Rab-20 (RAB20) affects the response to substance of Etoposide.	[24]
Mitomycin	DMH0ZJE	Approved	Ras-related protein Rab-20 (RAB20) affects the response to substance of Mitomycin.	[24]
Topotecan	DMP6G8T	Approved	Ras-related protein Rab-20 (RAB20) affects the response to substance of Topotecan.	[24]

1 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-20 (RAB20).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-20 (RAB20).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related protein Rab-20 (RAB20).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ras-related protein Rab-20 (RAB20).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ras-related protein Rab-20 (RAB20).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ras-related protein Rab-20 (RAB20).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ras-related protein Rab-20 (RAB20).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Ras-related protein Rab-20 (RAB20).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ras-related protein Rab-20 (RAB20).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Ras-related protein Rab-20 (RAB20).	[16]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Ras-related protein Rab-20 (RAB20).	[17]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Ras-related protein Rab-20 (RAB20).	[18]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ras-related protein Rab-20 (RAB20).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras-related protein Rab-20 (RAB20).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras-related protein Rab-20 (RAB20).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-related protein Rab-20 (RAB20).	[21]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Ras-related protein Rab-20 (RAB20).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related protein Rab-20 (RAB20).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ras-related protein Rab-20 (RAB20).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ras-related protein Rab-20 (RAB20).	[23]

References

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• [2] Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma.Mod Pathol. 2011 Apr;24(4):542-55. doi: 10.1038/modpathol.2010.217. Epub 2010 Nov 19.
• [3] Identification of novel Sp1 targets involved in proliferation and cancer by functional genomics.Biochem Pharmacol. 2012 Dec 15;84(12):1581-91. doi: 10.1016/j.bcp.2012.09.014. Epub 2012 Sep 25.
• [4] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [5] Characterization of human Rab20 overexpressed in exocrine pancreatic carcinoma.Hum Pathol. 2006 Mar;37(3):256-63. doi: 10.1016/j.humpath.2005.10.017.
• [6] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [7] Rab20 is critical for bacterial lipoprotein tolerization-enhanced bactericidal activity in macrophages during bacterial infection.Sci China Life Sci. 2020 Mar;63(3):401-409. doi: 10.1007/s11427-019-9527-3. Epub 2019 May 31.
• [8] 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.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] 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.
• [14] 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.
• [15] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [18] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [19] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [20] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [21] 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.
• [22] 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.
• [23] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.