Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO6D2GZ)

• DOT Name: Multivesicular body subunit 12B (MVB12B)
• Synonyms: ESCRT-I complex subunit MVB12B; Protein FAM125B
• Gene Name: MVB12B
• Related Disease:
  OPTN-related open angle glaucoma
  Glaucoma/ocular hypertension
• UniProt ID: MB12B_HUMAN
• PDB ID: 3TOW
• Pfam ID: PF10240
• Sequence:
  MRSCFCVRRSRDPPPPQPPPPPPQRGTDQSTMPEVKDLSEALPETSMDPITGVGVVASRN
  RAPTGYDVVAQTADGVDADLWKDGLFKSKVTRYLCFTRSFSKENSHLGNVLVDMKLIDIK
  DTLPVGFIPIQETVDTQEVAFRKKRLCIKFIPRDSTEAAICDIRIMGRTKQAPPQYTFIG
  ELNSMGIWYRMGRVPRNHDSSQPTTPSQSSAASTPAPNLPRHISLTLPATFRGRNSTRTD
  YEYQHSNLYAISAMDGVPFMISEKFSCVPESMQPFDLLGITIKSLAEIEKEYEYSFRTEQ
  SAAARLPPSPTRCQQIPQS
• Function: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  Membrane binding and targetting of GAG proteins (R-HSA-174490)
  Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729)
  HCMV Late Events (R-HSA-9610379)
  Late endosomal microautophagy (R-HSA-9615710)
  Budding and maturation of HIV virion (R-HSA-162588)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
OPTN-related open angle glaucoma	DISDR98A	Definitive	Biomarker	[1]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[2]

9 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 Multivesicular body subunit 12B (MVB12B).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Multivesicular body subunit 12B (MVB12B).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Multivesicular body subunit 12B (MVB12B).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Multivesicular body subunit 12B (MVB12B).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Multivesicular body subunit 12B (MVB12B).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Multivesicular body subunit 12B (MVB12B).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Multivesicular body subunit 12B (MVB12B).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Multivesicular body subunit 12B (MVB12B).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Multivesicular body subunit 12B (MVB12B).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Multivesicular body subunit 12B (MVB12B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Multivesicular body subunit 12B (MVB12B).	[13]

References

• [1] Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma.PLoS One. 2017 Aug 23;12(8):e0183709. doi: 10.1371/journal.pone.0183709. eCollection 2017.
• [2] A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort.Hum Mol Genet. 2014 Jun 15;23(12):3343-8. doi: 10.1093/hmg/ddu050. Epub 2014 Feb 11.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Real-time monitoring of cisplatin-induced cell death. PLoS One. 2011;6(5):e19714. doi: 10.1371/journal.pone.0019714. Epub 2011 May 16.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] 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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.