Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT06PN42)

• DOT Name: Ras-related protein Rab-5B (RAB5B)
• Synonyms: EC 3.6.5.2
• Gene Name: RAB5B
• Related Disease:
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Breast cancer
  Breast carcinoma
  Gastroesophageal reflux disease
  Hepatitis B virus infection
  Hyperinsulinemia
  Hypothyroidism
  Neoplasm
  Non-insulin dependent diabetes
  Polycystic ovarian syndrome
  STAT3-related early-onset multisystem autoimmune disease
  Type-1 diabetes
  Asthma
  Metastatic melanoma
• UniProt ID: RAB5B_HUMAN
• PDB ID: 2HEI
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MTSRSTARPNGQPQASKICQFKLVLLGESAVGKSSLVLRFVKGQFHEYQESTIGAAFLTQ
  SVCLDDTTVKFEIWDTAGQERYHSLAPMYYRGAQAAIVVYDITNQETFARAKTWVKELQR
  QASPSIVIALAGNKADLANKRMVEYEEAQAYADDNSLLFMETSAKTAMNVNDLFLAIAKK
  LPKSEPQNLGGAAGRSRGVDLHEQSQQNKSQCCSN
• Function: Protein transport. Probably involved in vesicular traffic.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Mitophagy - animal (hsa04137)
  Endocytosis (hsa04144)
  Phagosome (hsa04145)
  Efferocytosis (hsa04148)
  Vasopressin-regulated water reabsorption (hsa04962)
  Salmonella infection (hsa05132)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  TBC/RABGAPs (R-HSA-8854214)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  RAB geranylgeranylation (R-HSA-8873719)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[1]
Autoimmune disease, susceptibility to, 6	DISHNUXI	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Genetic Variation	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[4]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[5]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[7]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	Strong	Genetic Variation	[1]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[8]
Asthma	DISW9QNS	Limited	Genetic Variation	[9]
Metastatic melanoma	DISSL43L	Limited	Altered Expression	[10]

8 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-5B (RAB5B).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ras-related protein Rab-5B (RAB5B).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-5B (RAB5B).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Ras-related protein Rab-5B (RAB5B).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ras-related protein Rab-5B (RAB5B).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-related protein Rab-5B (RAB5B).	[16]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Ras-related protein Rab-5B (RAB5B).	[17]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Ras-related protein Rab-5B (RAB5B).	[18]

References

• [1] 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.
• [2] MiR-130a-3p inhibits migration and invasion by regulating RAB5B in human breast cancer stem cell-like cells.Biochem Biophys Res Commun. 2018 Jun 22;501(2):486-493. doi: 10.1016/j.bbrc.2018.05.018. Epub 2018 May 10.
• [3] Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.Nat Commun. 2019 Sep 16;10(1):4219. doi: 10.1038/s41467-019-11968-2.
• [4] Small Interfering RNA Screening for the Small GTPase Rab Proteins Identifies Rab5B as a Major Regulator of Hepatitis B Virus Production.J Virol. 2019 Jul 17;93(15):e00621-19. doi: 10.1128/JVI.00621-19. Print 2019 Aug 1.
• [5] Cloning of Rab GTPases expressed in human skeletal muscle: studies in insulin-resistant subjects.Horm Metab Res. 1998 Nov;30(11):656-62. doi: 10.1055/s-2007-978953.
• [6] Deep Sequencing Reveals a Novel miR-22 Regulatory Network with Therapeutic Potential in Rhabdomyosarcoma.Cancer Res. 2016 Oct 15;76(20):6095-6106. doi: 10.1158/0008-5472.CAN-16-0709. Epub 2016 Aug 28.
• [7] Association between Common Genetic Variants and Polycystic Ovary Syndrome Risk in a Chinese Han Population.J Clin Res Pediatr Endocrinol. 2016 Dec 1;8(4):405-410. doi: 10.4274/jcrpe.2784. Epub 2016 May 23.
• [8] Identification of Novel T1D Risk Loci and Their Association With Age and Islet Function at Diagnosis in Autoantibody-Positive T1D Individuals: Based on a Two-Stage Genome-Wide Association Study.Diabetes Care. 2019 Aug;42(8):1414-1421. doi: 10.2337/dc18-2023. Epub 2019 May 31.
• [9] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [10] Gene expression patterns in melanocytic cells: candidate markers for early stage and malignant transformation.J Pathol. 2002 Jan;196(1):51-8. doi: 10.1002/path.1017.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [17] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [18] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.