Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJQYRC7)

• DOT Name: Unconventional myosin-VI (MYO6)
• Synonyms: Unconventional myosin-6
• Gene Name: MYO6
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Nonsyndromic genetic hearing loss
  Alzheimer disease
  Autosomal dominant nonsyndromic hearing loss 22
  Autosomal recessive nonsyndromic hearing loss 37
  Cardiac disease
  Cardiomyopathy
  Colorectal carcinoma
  Deafness
  Drug dependence
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  High blood pressure
  Myopathy
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate neoplasm
  Sensorineural hearing loss disorder
  Substance abuse
  Substance dependence
  Adenovirus infection
  Lung cancer
  Lung carcinoma
  Melanoma
  Prostate carcinoma
  Skin cancer
  Autosomal dominant nonsyndromic hearing loss
  Hearing loss, autosomal recessive
  Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome
  Advanced cancer
  Amyotrophic lateral sclerosis
  Gastric cancer
  Prostate cancer
  Stomach cancer
  Stroke
• UniProt ID: MYO6_HUMAN
• PDB ID: 2N0Z; 2N10; 2N11; 2N12; 2N13; 6E5N; 6J56
• Pfam ID: PF21521 ; PF16521 ; PF00063
• Sequence:
  MEDGKPVWAPHPTDGFQMGNIVDIGPDSLTIEPLNQKGKTFLALINQVFPAEEDSKKDVE
  DNCSLMYLNEATLLHNIKVRYSKDRIYTYVANILIAVNPYFDIPKIYSSEAIKSYQGKSL
  GTRPPHVFAIADKAFRDMKVLKMSQSIIVSGESGAGKTENTKFVLRYLTESYGTGQDIDD
  RIVEANPLLEAFGNAKTVRNNNSSRFGKFVEIHFNEKSSVVGGFVSHYLLEKSRICVQGK
  EERNYHIFYRLCAGASEDIREKLHLSSPDNFRYLNRGCTRYFANKETDKQILQNRKSPEY
  LKAGSMKDPLLDDHGDFIRMCTAMKKIGLDDEEKLDLFRVVAGVLHLGNIDFEEAGSTSG
  GCNLKNKSAQSLEYCAELLGLDQDDLRVSLTTRVMLTTAGGTKGTVIKVPLKVEQANNAR
  DALAKTVYSHLFDHVVNRVNQCFPFETSSYFIGVLDIAGFEYFEHNSFEQFCINYCNEKL
  QQFFNERILKEEQELYQKEGLGVNEVHYVDNQDCIDLIEAKLVGILDILDEENRLPQPSD
  QHFTSAVHQKHKDHFRLTIPRKSKLAVHRNIRDDEGFIIRHFAGAVCYETTQFVEKNNDA
  LHMSLESLICESRDKFIRELFESSTNNNKDTKQKAGKLSFISVGNKFKTQLNLLLDKLRS
  TGASFIRCIKPNLKMTSHHFEGAQILSQLQCSGMVSVLDLMQGGYPSRASFHELYNMYKK
  YMPDKLARLDPRLFCKALFKALGLNENDYKFGLTKVFFRPGKFAEFDQIMKSDPDHLAEL
  VKRVNHWLTCSRWKKVQWCSLSVIKLKNKIKYRAEACIKMQKTIRMWLCKRRHKPRIDGL
  VKVGTLKKRLDKFNEVVSVLKDGKPEMNKQIKNLEISIDTLMAKIKSTMMTQEQIQKEYD
  ALVKSSEELLSALQKKKQQEEEAERLRRIQEEMEKERKRREEDEKRRRKEEEERRMKLEM
  EAKRKQEEEERKKREDDEKRIQAEVEAQLARQKEEESQQQAVLEQERRDRELALRIAQSE
  AELISDEAQADLALRRSLDSYPVSKNDGTRPKMTPEQMAKEMSEFLSRGPAVLATKAAAG
  TKKYDLSKWKYAELRDTINTSCDIELLAACREEFHRRLKVYHAWKSKNKKRNTETEQRAP
  KSVTDYDFAPFLNNSPQQNPAAQIPARQREIEMNRQQRFFRIPFIRPADQYKDPQSKKKG
  WWYAHFDGPWIARQMELHPDKPPILLVAGKDDMEMCELNLEETGLTRKRGAEILPRQFEE
  IWERCGGIQYLQNAIESRQARPTYATAMLQSLLK
• Function: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. Together with TOM1, mediates delivery of endocytic cargo to autophagosomes thereby promoting autophagosome maturation and driving fusion with lysosomes. Links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN. May act as a regulator of F-actin dynamics. As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. May play a role in the extension and network organization of neurites. Required for structural integrity of inner ear hair cells. Modulates RNA polymerase II-dependent transcription.
• Tissue Specificity: Expressed in most tissues examined including heart, brain, placenta, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in brain, pancreas, testis and small intestine. Also expressed in fetal brain and cochlea. Isoform 1 and isoform 2, containing the small insert, and isoform 4, containing neither insert, are expressed in unpolarized epithelial cells.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Trafficking of AMPA receptors (R-HSA-399719)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  RHOU GTPase cycle (R-HSA-9013420)
  RHOBTB1 GTPase cycle (R-HSA-9013422)
  Gap junction degradation (R-HSA-190873)

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Nonsyndromic genetic hearing loss	DISZX61P	Definitive	Autosomal dominant	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Autosomal dominant nonsyndromic hearing loss 22	DISHLH3F	Strong	Autosomal dominant	[5]
Autosomal recessive nonsyndromic hearing loss 37	DISW62TK	Strong	Autosomal recessive	[5]
Cardiac disease	DISVO1I5	Strong	Biomarker	[6]
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Deafness	DISKCLH4	Strong	Genetic Variation	[9]
Drug dependence	DIS9IXRC	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	Strong	Biomarker	[13]
Myopathy	DISOWG27	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[16]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[17]
Substance abuse	DIS327VW	Strong	Biomarker	[10]
Substance dependence	DISDRAAR	Strong	Biomarker	[10]
Adenovirus infection	DISUYSBZ	moderate	Altered Expression	[18]
Lung cancer	DISCM4YA	moderate	Altered Expression	[19]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[19]
Melanoma	DIS1RRCY	moderate	Biomarker	[20]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[21]
Skin cancer	DISTM18U	moderate	Biomarker	[20]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[22]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[22]
Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome	DISXZN77	Supportive	Autosomal dominant	[23]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[24]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[25]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[26]
Prostate cancer	DISF190Y	Limited	Biomarker	[27]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[26]
Stroke	DISX6UHX	Limited	Biomarker	[28]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Unconventional myosin-VI (MYO6) affects the response to substance of Methotrexate.	[51]
Fluorouracil	DMUM7HZ	Approved	Unconventional myosin-VI (MYO6) affects the response to substance of Fluorouracil.	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Unconventional myosin-VI (MYO6).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Unconventional myosin-VI (MYO6).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Unconventional myosin-VI (MYO6).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Unconventional myosin-VI (MYO6).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Unconventional myosin-VI (MYO6).	[33]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Unconventional myosin-VI (MYO6).	[34]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Unconventional myosin-VI (MYO6).	[35]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Unconventional myosin-VI (MYO6).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Unconventional myosin-VI (MYO6).	[37]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Unconventional myosin-VI (MYO6).	[38]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Unconventional myosin-VI (MYO6).	[39]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Unconventional myosin-VI (MYO6).	[40]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Unconventional myosin-VI (MYO6).	[41]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Unconventional myosin-VI (MYO6).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Unconventional myosin-VI (MYO6).	[35]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Unconventional myosin-VI (MYO6).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Unconventional myosin-VI (MYO6).	[43]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Unconventional myosin-VI (MYO6).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Unconventional myosin-VI (MYO6).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Unconventional myosin-VI (MYO6).	[47]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Unconventional myosin-VI (MYO6).	[48]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Unconventional myosin-VI (MYO6).	[49]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Unconventional myosin-VI (MYO6).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Unconventional myosin-VI (MYO6).	[44]

References

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