Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHE4ZEK)

• DOT Name: Midnolin (MIDN)
• Synonyms: Midbrain nucleolar protein
• Gene Name: MIDN
• Related Disease: Parkinson disease
• UniProt ID: MIDN_HUMAN
• Pfam ID: PF00240
• Sequence:
  MEPQPGGARSCRRGAPGGACELGPAAEAAPMSLAIHSTTGTRYDLAVPPDETVEGLRKRL
  SQRLKVPKERLALLHKDTRLSSGKLQEFGVGDGSKLTLVPTVEAGLMSQASRPEQSVMQA
  LESLTETQVSDFLSGRSPLTLALRVGDHMMFVQLQLAAQHAPLQHRHVLAAAAAAAAARG
  DPSIASPVSSPCRPVSSAARVPPVPTSPSPASPSPITAGSFRSHAASTTCPEQMDCSPTA
  SSSASPGASTTSTPGASPAPRSRKPGAVIESFVNHAPGVFSGTFSGTLHPNCQDSSGRPR
  RDIGTILQILNDLLSATRHYQGMPPSLAQLRCHAQCSPASPAPDLAPRTTSCEKLTAAPS
  ASLLQGQSQIRMCKPPGDRLRQTENRATRCKVERLQLLLQQKRLRRKARRDARGPYHWSP
  SRKAGRSDSSSSGGGGSPSEASGLGLDFEDSVWKPEVNPDIKSEFVVA
• Function: Facilitates the ubiquitin-independent proteasomal degradation of stimulus-induced transcription factors such as FOSB, EGR1, NR4A1, and IRF4 to the proteasome for degradation. Promotes also the degradation of other substrates such as CBX4. Plays a role in inhibiting the activity of glucokinase GCK and both glucose-induced and basal insulin secretion.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Midnolin (MIDN).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Midnolin (MIDN).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Midnolin (MIDN).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Midnolin (MIDN).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Midnolin (MIDN).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Midnolin (MIDN).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Midnolin (MIDN).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Midnolin (MIDN).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Midnolin (MIDN).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Midnolin (MIDN).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Midnolin (MIDN).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Midnolin (MIDN).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Midnolin (MIDN).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Midnolin (MIDN).	[15]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Midnolin (MIDN).	[16]

References

• [1] Midnolin is a confirmed genetic risk factor for Parkinson's disease.Ann Clin Transl Neurol. 2019 Nov;6(11):2205-2211. doi: 10.1002/acn3.50914. Epub 2019 Oct 6.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] 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.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [15] 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.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.