Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPZ3EJL)

• DOT Name: Ras-related protein Rab-33B (RAB33B)
• Gene Name: RAB33B
• Related Disease:
  Hepatitis B virus infection
  Smith-McCort dysplasia 1
  Smith-McCort dysplasia 2
  Smith-McCort dysplasia
• UniProt ID: RB33B_HUMAN
• PDB ID: 6Y09; 6ZAY
• Pfam ID: PF00071
• Sequence:
  MAEEMESSLEASFSSSGAVSGASGFLPPARSRIFKIIVIGDSNVGKTCLTYRFCAGRFPD
  RTEATIGVDFRERAVEIDGERIKIQLWDTAGQERFRKSMVQHYYRNVHAVVFVYDMTNMA
  SFHSLPSWIEECKQHLLANDIPRILVGNKCDLRSAIQVPTDLAQKFADTHSMPLFETSAK
  NPNDNDHVEAIFMTLAHKLKSHKPLMLSQPPDNGIILKPEPKPAMTCWC
• Function: Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking. It is involved in autophagy, acting as a modulator of autophagosome formation.
• KEGG Pathway: Autophagy - animal (hsa04140)
• Reactome Pathway:
  TBC/RABGAPs (R-HSA-8854214)
  RAB geranylgeranylation (R-HSA-8873719)
  Intra-Golgi traffic (R-HSA-6811438)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[1]
Smith-McCort dysplasia 1	DIS8072R	Strong	Genetic Variation	[2]
Smith-McCort dysplasia 2	DISX2MMO	Strong	Autosomal recessive	[3]
Smith-McCort dysplasia	DIS18P12	Supportive	Autosomal recessive	[3]

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-33B (RAB33B).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Rab-33B (RAB33B).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-related protein Rab-33B (RAB33B).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ras-related protein Rab-33B (RAB33B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-related protein Rab-33B (RAB33B).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ras-related protein Rab-33B (RAB33B).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-related protein Rab-33B (RAB33B).	[10]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Ras-related protein Rab-33B (RAB33B).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ras-related protein Rab-33B (RAB33B).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ras-related protein Rab-33B (RAB33B).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ras-related protein Rab-33B (RAB33B).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ras-related protein Rab-33B (RAB33B).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Ras-related protein Rab-33B (RAB33B).	[16]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Ras-related protein Rab-33B (RAB33B).	[17]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Ras-related protein Rab-33B (RAB33B).	[18]

References

• [1] Rab33B Controls Hepatitis B Virus Assembly by Regulating Core Membrane Association and Nucleocapsid Processing.Viruses. 2017 Jun 21;9(6):157. doi: 10.3390/v9060157.
• [2] A novel RAB33B mutation in Smith-McCort dysplasia.Hum Mutat. 2013 Feb;34(2):283-6. doi: 10.1002/humu.22235. Epub 2012 Nov 8.
• [3] Mutation in RAB33B, which encodes a regulator of retrograde Golgi transport, defines a second Dyggve--Melchior--Clausen locus. J Med Genet. 2012 Jul;49(7):455-61. doi: 10.1136/jmedgenet-2011-100666. Epub 2012 May 31.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] 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.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [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.