Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3737K0)

• DOT Name: Multivesicular body subunit 12A (MVB12A)
• Synonyms: CIN85/CD2AP family-binding protein; ESCRT-I complex subunit MVB12A; Protein FAM125A
• Gene Name: MVB12A
• UniProt ID: MB12A_HUMAN
• PDB ID: 6VME
• Pfam ID: PF10240
• Sequence:
  MDPVPGTDSAPLAGLAWSSASAPPPRGFSAISCTVEGAPASFGKSFAQKSGYFLCLSSLG
  SLENPQENVVADIQIVVDKSPLPLGFSPVCDPMDSKASVSKKKRMCVKLLPLGATDTAVF
  DVRLSGKTKTVPGYLRIGDMGGFAIWCKKAKAPRPVPKPRGLSRDMQGLSLDAASQPSKG
  GLLERTASRLGSRASTLRRNDSIYEASSLYGISAMDGVPFTLHPRFEGKSCSPLAFSAFG
  DLTIKSLADIEEEYNYGFVVEKTAAARLPPSVS
• Function: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor.
• Tissue Specificity: Ubiquitously expressed except in skeletal muscle.
• 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

9 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 Multivesicular body subunit 12A (MVB12A).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Multivesicular body subunit 12A (MVB12A).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Multivesicular body subunit 12A (MVB12A).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Multivesicular body subunit 12A (MVB12A).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Multivesicular body subunit 12A (MVB12A).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Multivesicular body subunit 12A (MVB12A).	[7]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Multivesicular body subunit 12A (MVB12A).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Multivesicular body subunit 12A (MVB12A).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Multivesicular body subunit 12A (MVB12A).	[11]

3 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 Multivesicular body subunit 12A (MVB12A).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Multivesicular body subunit 12A (MVB12A).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Multivesicular body subunit 12A (MVB12A).	[12]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] 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.
• [8] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [9] 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.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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.