Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6SK83U)

• DOT Name: Ras-related protein Rab-2A (RAB2A)
• Synonyms: EC 3.6.5.2
• Gene Name: RAB2A
• Related Disease:
  Acute erythroid leukemia
  Advanced cancer
  Autism spectrum disorder
  Glioma
  Oral cancer
  Polycystic ovarian syndrome
  Breast cancer
  Breast carcinoma
  Pancreatic ductal carcinoma
  Patent ductus arteriosus
  Squamous cell carcinoma
• UniProt ID: RAB2A_HUMAN
• PDB ID: 1Z0A
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MAYAYLFKYIIIGDTGVGKSCLLLQFTDKRFQPVHDLTIGVEFGARMITIDGKQIKLQIW
  DTAGQESFRSITRSYYRGAAGALLVYDITRRDTFNHLTTWLEDARQHSNSNMVIMLIGNK
  SDLESRREVKKEEGEAFAREHGLIFMETSAKTASNVEEAFINTAKEIYEKIQEGVFDINN
  EANGIKIGPQHAATNATHAGNQGGQQAGGGCC
• Function: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology. Required for protein transport from the endoplasmic reticulum to the Golgi complex. Regulates the compacted morphology of the Golgi.
• KEGG Pathway: AMPK sig.ling pathway (hsa04152)
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  Golgi Cisternae Pericentriolar Stack Reorganization (R-HSA-162658)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute erythroid leukemia	DISZFC1O	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Oral cancer	DISLD42D	Strong	Altered Expression	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[7]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[8]
Patent ductus arteriosus	DIS9P8YS	moderate	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ras-related protein Rab-2A (RAB2A).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-2A (RAB2A).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ras-related protein Rab-2A (RAB2A).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-2A (RAB2A).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ras-related protein Rab-2A (RAB2A).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ras-related protein Rab-2A (RAB2A).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ras-related protein Rab-2A (RAB2A).	[17]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Ras-related protein Rab-2A (RAB2A).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Ras-related protein Rab-2A (RAB2A).	[19]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Ras-related protein Rab-2A (RAB2A).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras-related protein Rab-2A (RAB2A).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-related protein Rab-2A (RAB2A).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-related protein Rab-2A (RAB2A).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ras-related protein Rab-2A (RAB2A).	[25]
GW7604	DMCA4RM	Investigative	GW7604 increases the expression of Ras-related protein Rab-2A (RAB2A).	[18]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ras-related protein Rab-2A (RAB2A).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ras-related protein Rab-2A (RAB2A).	[23]

References

• [1] Localization of the human oncogene SPI1 on chromosome 11, region p11.22.Hum Genet. 1990 May;84(6):542-6. doi: 10.1007/BF00210807.
• [2] Overexpression of the ras-related rab2 gene product in peripheral blood mononuclear cells from patients with hematological and solid neoplasms.Cancer Res. 1992 Jun 1;52(11):3083-8.
• [3] De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.Neuron. 2016 Mar 2;89(5):940-7. doi: 10.1016/j.neuron.2016.02.024.
• [4] Over-expression of Rap2a inhibits glioma migration and invasion by down-regulating p-AKT.Cell Biol Int. 2014 Mar;38(3):326-34. doi: 10.1002/cbin.10213. Epub 2013 Dec 2.
• [5] S100A7 has an oncogenic role in oral squamous cell carcinoma by activating p38/MAPK and RAB2A signaling pathway.Cancer Gene Ther. 2016 Nov;23(11):382-391. doi: 10.1038/cgt.2016.43. Epub 2016 Oct 21.
• [6] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [7] RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer programs.EMBO Rep. 2016 Jul;17(7):1061-80. doi: 10.15252/embr.201642032. Epub 2016 Jun 2.
• [8] Oncogenicity of LHX2 in pancreatic ductal adenocarcinoma.Mol Biol Rep. 2014 Dec;41(12):8163-7. doi: 10.1007/s11033-014-3716-2. Epub 2014 Oct 17.
• [9] Identification of RAB2A and PRDX1 as the potential biomarkers for oral squamous cell carcinoma using mass spectrometry-based comparative proteomic approach.Tumour Biol. 2015 Dec;36(12):9829-37. doi: 10.1007/s13277-015-3758-7. Epub 2015 Jul 11.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] 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.
• [14] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [15] Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [18] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [19] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [20] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [21] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [22] 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.
• [23] 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.
• [24] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [25] 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.