Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPM8PHS)

DOT Name Myosin-IIIa (MYO3A)
Synonyms EC 2.7.11.1
Gene Name MYO3A
Related Disease
Nonsyndromic genetic hearing loss ( )
Autosomal recessive nonsyndromic hearing loss 30 ( )
Deafness ( )
Sensorineural hearing loss disorder ( )
Hearing loss, autosomal recessive ( )
Colorectal carcinoma ( )
UniProt ID
MYO3A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6JLE
EC Number
2.7.11.1
Pfam ID
PF00612 ; PF00063 ; PF00069
Sequence
MFPLIGKTIIFDNFPDPSDTWEITETIGKGTYGKVFKVLNKKNGQKAAVKILDPIHDIDE
EIEAEYNILKALSDHPNVVRFYGIYFKKDKVNGDKLWLVLELCSGGSVTDLVKGFLKRGE
RMSEPLIAYILHEALMGLQHLHNNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQLTSTRH
RRNTSVGTPFWMAPEVIACEQQLDTTYDARCDTWSLGITAIELGDGDPPLADLHPMRALF
KIPRNPPPKLRQPELWSAEFNDFISKCLTKDYEKRPTVSELLQHKFITQIEGKDVMLQKQ
LTEFIGIHQCMGGTEKARRERIHTKKGNFNRPLISNLKDVDDLATLEILDENTVSEQLEK
CYSRDQIYVYVGDILIALNPFQSLGLYSTKHSKLYIGSKRTASPPHIFAMADLGYQSMIT
YNSDQCIVISGESGAGKTENAHLLVQQLTVLGKANNRTLQEKILQVNNLVEAFGNACTII
NDNSSRFGKYLEMKFTSSGAVVGAQISEYLLEKSRVIHQAIGEKNFHIFYYIYAGLAEKK
KLAHYKLPENKPPRYLQNDHLRTVQDIMNNSFYKSQYELIEQCFKVIGFTMEQLGSIYSI
LAAILNVGNIEFSSVATEHQIDKSHISNHTALENCASLLCIRADELQEALTSHCVVTRGE
TIIRPNTVEKATDVRDAMAKTLYGRLFSWIVNCINSLLKHDSSPSGNGDELSIGILDIFG
FENFKKNSFEQLCINIANEQIQYYYNQHVFAWEQNEYLNEDVDARVIEYEDNWPLLDMFL
QKPMGLLSLLDEESRFPKATDQTLVEKFEGNLKSQYFWRPKRMELSFGIHHYAGKVLYNA
SGFLAKNRDTLPTDIVLLLRSSDNSVIRQLVNHPLTKTGNLPHSKTKNVINYQMRTSEKL
INLAKGDTGEATRHARETTNMKTQTVASYFRYSLMDLLSKMVVGQPHFVRCIKPNSERQA
RKYDKEKVLLQLRYTGILETARIRRLGFSHRILFANFIKRYYLLCYKSSEEPRMSPDTCA
TILEKAGLDNWALGKTKVFLKYYHVEQLNLMRKEAIDKLILIQACVRAFLCSRRYQKIQE
KRKESAIIIQSAARGHLVRKQRKEIVDMKNTAVTTIQTSDQEFDYKKNFENTRESFVKKQ
AENAISANERFISAPNNKGSVSVVKTSTFKPEEETTNAVESNNRVYQTPKKMNNVYEEEV
KQEFYLVGPEVSPKQKSVKDLEENSNLRKVEKEEAMIQSYYQRYTEERNCEESKAAYLER
KAISERPSYPVPWLAENETSFKKTLEPTLSQRSIYQNANSMEKEKKTSVVTQRAPICSQE
EGRGRLRHETVKERQVEPVTQAQEEEDKAAVFIQSKYRGYKRRQQLRKDKMSSFKHQRIV
TTPTEVARNTHNLYSYPTKHEEINNIKKKDNKDSKATSEREACGLAIFSKQISKLSEEYF
ILQKKLNEMILSQQLKSLYLGVSHHKPINRRVSSQQCLSGVCKGEEPKILRPPRRPRKPK
TLNNPEDSTYYYLLHKSIQEEKRRPRKDSQGKLLDLEDFYYKEFLPSRSGPKEHSPSLRE
RRPQQELQNQCIKANERCWAAESPEKEEEREPAANPYDFRRLLRKTSQRRRLVQQS
Function
Probable actin-based motor with a protein kinase activity. Probably plays a role in vision and hearing. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments.
Tissue Specificity Strongest expression in retina, retinal pigment epithelial cells, cochlea and pancreas.
KEGG Pathway
Motor proteins (hsa04814 )
Reactome Pathway
Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361 )
Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Nonsyndromic genetic hearing loss DISZX61P Definitive Autosomal recessive [1]
Autosomal recessive nonsyndromic hearing loss 30 DISA15TJ Strong Autosomal recessive [2]
Deafness DISKCLH4 Strong Genetic Variation [3]
Sensorineural hearing loss disorder DISJV45Z moderate Genetic Variation [4]
Hearing loss, autosomal recessive DIS8G9R9 Supportive Autosomal recessive [5]
Colorectal carcinoma DIS5PYL0 Limited Genetic Variation [6]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Myosin-IIIa (MYO3A). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Myosin-IIIa (MYO3A). [8]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Myosin-IIIa (MYO3A). [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 increases the methylation of Myosin-IIIa (MYO3A). [10]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA. Mamm Genome. 2011 Apr;22(3-4):170-7. doi: 10.1007/s00335-010-9310-6. Epub 2010 Dec 17.
3 Identification of a novel homozygous mutation in MYO3A in a Chinese family with DFNB30 non-syndromic hearing impairment.Int J Pediatr Otorhinolaryngol. 2016 May;84:43-7. doi: 10.1016/j.ijporl.2016.02.036. Epub 2016 Mar 5.
4 A study of GJB2 and delGJB6-D13S1830 mutations in Brazilian non-syndromic deaf children from the Amazon region.Braz J Otorhinolaryngol. 2013 Jan-Feb;79(1):95-9. doi: 10.5935/1808-8694.20130016.
5 Genetic Hearing Loss Overview. 1999 Feb 14 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
6 Genome-wide association study for colorectal cancer identifies risk polymorphisms in German familial cases and implicates MAPK signalling pathways in disease susceptibility.Carcinogenesis. 2010 Sep;31(9):1612-9. doi: 10.1093/carcin/bgq146. Epub 2010 Jul 7.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 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.
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.