Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYKQ9O5)

DOT Name Protein unc-45 homolog B
Synonyms Unc-45B; SMUNC45
Gene Name UNC45B
Related Disease
Cataract 43 ( )
Myofibrillar myopathy 11 ( )
Early-onset nuclear cataract ( )
Early-onset posterior subcapsular cataract ( )
UniProt ID
UN45B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF11701
Sequence
MAEVEAVQLKEEGNRHFQLQDYKAATNSYSQALKLTKDKALLATLYRNRAACGLKTESYV
QAASDASRAIDINSSDIKALYRRCQALEHLGKLDQAFKDVQRCATLEPRNQNFQEMLRRL
NTSIQEKLRVQFSTDSRVQKMFEILLDENSEADKREKAANNLIVLGREEAGAEKIFQNNG
VALLLQLLDTKKPELVLAAVRTLSGMCSGHQARATVILHAVRIDRICSLMAVENEEMSLA
VCNLLQAIIDSLSGEDKREHRGKEEALVLDTKKDLKQITSHLLDMLVSKKVSGQGRDQAL
NLLNKNVPRKDLAIHDNSRTIYVVDNGLRKILKVVGQVPDLPSCLPLTDNTRMLASILIN
KLYDDLRCDPERDHFRKICEEYITGKFDPQDMDKNLNAIQTVSGILQGPFDLGNQLLGLK
GVMEMMVALCGSERETDQLVAVEALIHASTKLSRATFIITNGVSLLKQIYKTTKNEKIKI
RTLVGLCKLGSAGGTDYGLRQFAEGSTEKLAKQCRKWLCNMSIDTRTRRWAVEGLAYLTL
DADVKDDFVQDVPALQAMFELAKAGTSDKTILYSVATTLVNCTNSYDVKEVIPELVQLAK
FSKQHVPEEHPKDKKDFIDMRVKRLLKAGVISALACMVKADSAILTDQTKELLARVFLAL
CDNPKDRGTIVAQGGGKALIPLALEGTDVGKVKAAHALAKIAAVSNPDIAFPGERVYEVV
RPLVRLLDTQRDGLQNYEALLGLTNLSGRSDKLRQKIFKERALPDIENYMFENHDQLRQA
ATECMCNMVLHKEVQERFLADGNDRLKLVVLLCGEDDDKVQNAAAGALAMLTAAHKKLCL
KMTQVTTQWLEILQRLCLHDQLSVQHRGLVIAYNLLAADAELAKKLVESELLEILTVVGK
QEPDEKKAEVVQTARECLIKCMDYGFIKPVS
Function
Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain. Plays a role in sarcomere formation during muscle cell development. Is necessary for normal early lens development.
Tissue Specificity Expressed in eye lens tissues. Expressed in muscle (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cataract 43 DISL9WIR Strong Autosomal dominant [1]
Myofibrillar myopathy 11 DISDFX9M Strong Autosomal recessive [2]
Early-onset nuclear cataract DISGIHUY Supportive Autosomal dominant [1]
Early-onset posterior subcapsular cataract DISB7SJS Supportive Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Protein unc-45 homolog B. [3]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein unc-45 homolog B. [8]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein unc-45 homolog B. [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Protein unc-45 homolog B. [5]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Protein unc-45 homolog B. [6]
Clozapine DMFC71L Approved Clozapine increases the expression of Protein unc-45 homolog B. [7]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Protein unc-45 homolog B. [9]
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References

1 The myosin chaperone UNC45B is involved in lens development and autosomal dominant juvenile cataract. Eur J Hum Genet. 2014 Nov;22(11):1290-7. doi: 10.1038/ejhg.2014.21. Epub 2014 Feb 19.
2 Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores. Am J Hum Genet. 2020 Dec 3;107(6):1078-1095. doi: 10.1016/j.ajhg.2020.11.002. Epub 2020 Nov 19.
3 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
4 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
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 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
7 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
8 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.
9 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.