Details of Drug Off-Target (DOT)

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

DOT Name Probable E3 ubiquitin-protein ligase MID2 (MID2)
Synonyms EC 2.3.2.27; Midin-2; Midline defect 2; Midline-2; RING finger protein 60; RING-type E3 ubiquitin transferase MID2; Tripartite motif-containing protein 1
Gene Name MID2
Related Disease
Intellectual disability, X-linked 1 ( )
FG syndrome ( )
X-linked intellectual disability ( )
X-linked Opitz G/BBB syndrome ( )
Intellectual disability ( )
Non-syndromic X-linked intellectual disability ( )
Intellectual disability, X-linked 101 ( )
UniProt ID
TRIM1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2DJA; 2DMK; 7QRZ
EC Number
2.3.2.27
Pfam ID
PF18568 ; PF00622 ; PF00643 ; PF13445
Sequence
MGESPASVVLNASGGLFSLKMETLESELTCPICLELFEDPLLLPCAHSLCFSCAHRILVS
SCSSGESIEPITAFQCPTCRYVISLNHRGLDGLKRNVTLQNIIDRFQKASVSGPNSPSES
RRERTYRPTTAMSSERIACQFCEQDPPRDAVKTCITCEVSYCDRCLRATHPNKKPFTSHR
LVEPVPDTHLRGITCLDHENEKVNMYCVSDDQLICALCKLVGRHRDHQVASLNDRFEKLK
QTLEMNLTNLVKRNSELENQMAKLIQICQQVEVNTAMHEAKLMEECDELVEIIQQRKQMI
AVKIKETKVMKLRKLAQQVANCRQCLERSTVLINQAEHILKENDQARFLQSAKNIAERVA
MATASSQVLIPDINFNDAFENFALDFSREKKLLEGLDYLTAPNPPSIREELCTASHDTIT
VHWISDDEFSISSYELQYTIFTGQANFISKSWCSWGLWPEIRKCKEAVSCSRLAGAPRGL
YNSVDSWMIVPNIKQNHYTVHGLQSGTRYIFIVKAINQAGSRNSEPTRLKTNSQPFKLDP
KMTHKKLKISNDGLQMEKDESSLKKSHTPERFSGTGCYGAAGNIFIDSGCHYWEVVMGSS
TWYAIGIAYKSAPKNEWIGKNASSWVFSRCNSNFVVRHNNKEMLVDVPPHLKRLGVLLDY
DNNMLSFYDPANSLHLHTFDVTFILPVCPTFTIWNKSLMILSGLPAPDFIDYPERQECNC
RPQESPYVSGMKTCH
Function
E3 ubiquitin ligase that plays a role in microtubule stabilization. Mediates the 'Lys-48'-linked polyubiquitination of LRRK2 to drive its localization to microtubules and its proteasomal degradation in neurons. This ubiquitination inhibits LRRK2 kinase activation by RAB29.
Tissue Specificity Low level in fetal kidney and lung, and in adult prostate, ovary and small intestine.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intellectual disability, X-linked 1 DISET38E Definitive GermlineCausalMutation [1]
FG syndrome DIS2MEFU Strong Biomarker [2]
X-linked intellectual disability DISYJBY3 Strong Genetic Variation [1]
X-linked Opitz G/BBB syndrome DISQ14EC Strong Biomarker [3]
Intellectual disability DISMBNXP moderate Biomarker [1]
Non-syndromic X-linked intellectual disability DIS71AI3 Supportive X-linked [1]
Intellectual disability, X-linked 101 DISA0LAP Limited Unknown [1]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Probable E3 ubiquitin-protein ligase MID2 (MID2). [4]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Probable E3 ubiquitin-protein ligase MID2 (MID2). [5]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Probable E3 ubiquitin-protein ligase MID2 (MID2). [6]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Probable E3 ubiquitin-protein ligase MID2 (MID2). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Probable E3 ubiquitin-protein ligase MID2 (MID2). [9]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Probable E3 ubiquitin-protein ligase MID2 (MID2). [8]
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References

1 Targeted deep resequencing identifies MID2 mutation for X-linked intellectual disability with varied disease severity in a large kindred from India. Hum Mutat. 2014 Jan;35(1):41-4. doi: 10.1002/humu.22453. Epub 2013 Oct 21.
2 An Xq22.3 duplication detected by comparative genomic hybridization microarray (Array-CGH) defines a new locus (FGS5) for FG syndrome.Am J Med Genet A. 2005 Dec 15;139(3):221-6. doi: 10.1002/ajmg.a.30991.
3 MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders.BMC Cell Biol. 2002;3:1. doi: 10.1186/1471-2121-3-1. Epub 2002 Jan 4.
4 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
5 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
6 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
7 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
8 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
9 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.