Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHMIMH6)

DOT Name Muskelin (MKLN1)
Gene Name MKLN1
Related Disease
Bipolar disorder ( )
Prion disease ( )
Alopecia ( )
Androgenetic alopecia ( )
Baldness, male pattern ( )
Lung carcinoma ( )
UniProt ID
MKLN1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF01344 ; PF13415 ; PF06588
Sequence
MAAGGAVAAAPECRLLPYALHKWSSFSSTYLPENILVDKPNDQSSRWSSESNYPPQYLIL
KLERPAIVQNITFGKYEKTHVCNLKKFKVFGGMNEENMTELLSSGLKNDYNKETFTLKHK
IDEQMFPCRFIKIVPLLSWGPSFNFSIWYVELSGIDDPDIVQPCLNWYSKYREQEAIRLC
LKHFRQHNYTEAFESLQKKTKIALEHPMLTDIHDKLVLKGDFDACEELIEKAVNDGLFNQ
YISQQEYKPRWSQIIPKSTKGDGEDNRPGMRGGHQMVIDVQTETVYLFGGWDGTQDLADF
WAYSVKENQWTCISRDTEKENGPSARSCHKMCIDIQRRQIYTLGRYLDSSVRNSKSLKSD
FYRYDIDTNTWMLLSEDTAADGGPKLVFDHQMCMDSEKHMIYTFGGRILTCNGSVDDSRA
SEPQFSGLFAFNCQCQTWKLLREDSCNAGPEDIQSRIGHCMLFHSKNRCLYVFGGQRSKT
YLNDFFSYDVDSDHVDIISDGTKKDSGMVPMTGFTQRATIDPELNEIHVLSGLSKDKEKR
EENVRNSFWIYDIVRNSWSCVYKNDQAAKDNPTKSLQEEEPCPRFAHQLVYDELHKVHYL
FGGNPGKSCSPKMRLDDFWSLKLCRPSKDYLLRHCKYLIRKHRFEEKAQVDPLSALKYLQ
NDLYITVDHSDPEETKEFQLLASALFKSGSDFTALGFSDVDHTYAQRTQLFDTLVNFFPD
SMTPPKGNLVDLITL
Function
Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation. Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bipolar disorder DISAM7J2 Strong Biomarker [1]
Prion disease DISOUMB0 Strong Biomarker [2]
Alopecia DIS37HU4 Limited Genetic Variation [3]
Androgenetic alopecia DISSJR1P Limited Genetic Variation [4]
Baldness, male pattern DIS9C9RO Limited Genetic Variation [4]
Lung carcinoma DISTR26C Limited Genetic Variation [5]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 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 Muskelin (MKLN1). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Muskelin (MKLN1). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Muskelin (MKLN1). [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Muskelin (MKLN1). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Muskelin (MKLN1). [11]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Muskelin (MKLN1). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Muskelin (MKLN1). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Muskelin (MKLN1). [13]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of Muskelin (MKLN1). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Muskelin (MKLN1). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Muskelin (MKLN1). [6]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Muskelin (MKLN1). [16]
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⏷ Show the Full List of 12 Drug(s)
1 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 Muskelin (MKLN1). [9]
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References

1 A genome wide association study suggests the association of muskelin with early onset bipolar disorder: Implications for a GABAergic epileptogenic neurogenesis model.J Affect Disord. 2017 Jan 15;208:120-129. doi: 10.1016/j.jad.2016.09.049. Epub 2016 Sep 30.
2 Muskelin Coordinates PrP(C) Lysosome versus Exosome Targeting and Impacts Prion Disease Progression.Neuron. 2018 Sep 19;99(6):1155-1169.e9. doi: 10.1016/j.neuron.2018.08.010. Epub 2018 Aug 30.
3 Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
4 GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
5 Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
6 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 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.
10 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.
11 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
12 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
13 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.
14 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
15 Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.