Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMWLP3E)

• DOT Name: Unconventional myosin-Va (MYO5A)
• Synonyms: Dilute myosin heavy chain, non-muscle; Myosin heavy chain 12; Myosin-12; Myoxin
• Gene Name: MYO5A
• Related Disease:
  Griscelli syndrome type 1
  Griscelli syndrome type 3
  Advanced cancer
  Colorectal carcinoma
  Hyperpigmentation of the skin
  Non-insulin dependent diabetes
  Overactive bladder
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Stroke
  Testicular cancer
  Adenovirus infection
  Hypopigmentation of the skin
  Laryngeal squamous cell carcinoma
  Neoplasm
  Breast cancer
  Breast carcinoma
  Melanoma
  Movement disorder
  Neuroblastoma
  Peripheral neuropathy
• UniProt ID: MYO5A_HUMAN
• PDB ID: 4D07; 4J5L; 4LLI; 4LX1; 4LX2; 5JCY; 5JCZ
• Pfam ID: PF01843 ; PF00612 ; PF00063
• Sequence:
  MAASELYTKFARVWIPDPEEVWKSAELLKDYKPGDKVLLLHLEEGKDLEYHLDPKTKELP
  HLRNPDILVGENDLTALSYLHEPAVLHNLRVRFIDSKLIYTYCGIVLVAINPYEQLPIYG
  EDIINAYSGQNMGDMDPHIFAVAEEAYKQMARDERNQSIIVSGESGAGKTVSAKYAMRYF
  ATVSGSASEANVEEKVLASNPIMESIGNAKTTRNDNSSRFGKYIEIGFDKRYRIIGANMR
  TYLLEKSRVVFQAEEERNYHIFYQLCASAKLPEFKMLRLGNADNFNYTKQGGSPVIEGVD
  DAKEMAHTRQACTLLGISESHQMGIFRILAGILHLGNVGFTSRDADSCTIPPKHEPLCIF
  CELMGVDYEEMCHWLCHRKLATATETYIKPISKLQATNARDALAKHIYAKLFNWIVDNVN
  QALHSAVKQHSFIGVLDIYGFETFEINSFEQFCINYANEKLQQQFNMHVFKLEQEEYMKE
  QIPWTLIDFYDNQPCINLIESKLGILDLLDEECKMPKGTDDTWAQKLYNTHLNKCALFEK
  PRLSNKAFIIQHFADKVEYQCEGFLEKNKDTVFEEQIKVLKSSKFKMLPELFQDDEKAIS
  PTSATSSGRTPLTRTPAKPTKGRPGQMAKEHKKTVGHQFRNSLHLLMETLNATTPHYVRC
  IKPNDFKFPFTFDEKRAVQQLRACGVLETIRISAAGFPSRWTYQEFFSRYRVLMKQKDVL
  SDRKQTCKNVLEKLILDKDKYQFGKTKIFFRAGQVAYLEKLRADKLRAACIRIQKTIRGW
  LLRKKYLRMRKAAITMQRYVRGYQARCYAKFLRRTKAATIIQKYWRMYVVRRRYKIRRAA
  TIVLQSYLRGFLARNRYRKILREHKAVIIQKRVRGWLARTHYKRSMHAIIYLQCCFRRMM
  AKRELKKLKIEARSVERYKKLHIGMENKIMQLQRKVDEQNKDYKCLVEKLTNLEGIYNSE
  TEKLRSDLERLQLSEEEAKVATGRVLSLQEEIAKLRKDLEQTRSEKKCIEEHADRYKQET
  EQLVSNLKEENTLLKQEKEALNHRIVQQAKEMTETMEKKLVEETKQLELDLNDERLRYQN
  LLNEFSRLEERYDDLKEEMTLMVHVPKPGHKRTDSTHSSNESEYIFSSEIAEMEDIPSRT
  EEPSEKKVPLDMSLFLKLQKRVTELEQEKQVMQDELDRKEEQVLRSKAKEEERPQIRGAE
  LEYESLKRQELESENKKLKNELNELRKALSEKSAPEVTAPGAPAYRVLMEQLTSVSEELD
  VRKEEVLILRSQLVSQKEAIQPKDDKNTMTDSTILLEDVQKMKDKGEIAQAYIGLKETNR
  SSALDYHELNEDGELWLVYEGLKQANRLLESQLQSQKRSHENEAEALRGEIQSLKEENNR
  QQQLLAQNLQLPPEARIEASLQHEITRLTNENLDLMEQLEKQDKTVRKLKKQLKVFAKKI
  GELEVGQMENISPGQIIDEPIRPVNIPRKEKDFQGMLEYKKEDEQKLVKNLILELKPRGV
  AVNLIPGLPAYILFMCVRHADYLNDDQKVRSLLTSTINSIKKVLKKRGDDFETVSFWLSN
  TCRFLHCLKQYSGEEGFMKHNTSRQNEHCLTNFDLAEYRQVLSDLAIQIYQQLVRVLENI
  LQPMIVSGMLEHETIQGVSGVKPTGLRKRTSSIADEGTYTLDSILRQLNSFHSVMCQHGM
  DPELIKQVVKQMFYIIGAITLNNLLLRKDMCSWSKGMQIRYNVSQLEEWLRDKNLMNSGA
  KETLEPLIQAAQLLQVKKKTDDDAEAICSMCNALTTAQIVKVLNLYTPVNEFEERVSVSF
  IRTIQMRLRDRKDSPQLLMDAKHIFPVTFPFNPSSLALETIQIPASLGLGFISRV
• Function: Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Involved in melanosome transport. Also mediates the transport of vesicles to the plasma membrane. May also be required for some polarization process involved in dendrite formation.
• Tissue Specificity: Detected in melanocytes.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Pathogenic Escherichia coli infection (hsa05130)
• Reactome Pathway:
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  Insulin processing (R-HSA-264876)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Griscelli syndrome type 1	DIS8VA00	Definitive	Autosomal recessive	[1]
Griscelli syndrome type 3	DISG4PY1	Definitive	Autosomal recessive	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Hyperpigmentation of the skin	DISQ205R	Strong	Biomarker	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[6]
Overactive bladder	DISQR5TD	Strong	Altered Expression	[6]
Prostate cancer	DISF190Y	Strong	Altered Expression	[7]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[7]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[8]
Stroke	DISX6UHX	Strong	Biomarker	[9]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[7]
Adenovirus infection	DISUYSBZ	moderate	Altered Expression	[10]
Hypopigmentation of the skin	DIS39YKC	moderate	Genetic Variation	[11]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[12]
Neoplasm	DISZKGEW	moderate	Altered Expression	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[13]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[13]
Melanoma	DIS1RRCY	Limited	Biomarker	[14]
Movement disorder	DISOJJ2D	Limited	Genetic Variation	[15]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[13]
Peripheral neuropathy	DIS7KN5G	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bortezomib	DMNO38U	Approved	Unconventional myosin-Va (MYO5A) increases the response to substance of Bortezomib.	[16]
Paclitaxel	DMLB81S	Approved	Unconventional myosin-Va (MYO5A) increases the response to substance of Paclitaxel.	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Unconventional myosin-Va (MYO5A).	[17]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Unconventional myosin-Va (MYO5A).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Unconventional myosin-Va (MYO5A).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Unconventional myosin-Va (MYO5A).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Unconventional myosin-Va (MYO5A).	[33]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Unconventional myosin-Va (MYO5A).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Unconventional myosin-Va (MYO5A).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Unconventional myosin-Va (MYO5A).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Unconventional myosin-Va (MYO5A).	[20]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Unconventional myosin-Va (MYO5A).	[21]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Unconventional myosin-Va (MYO5A).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Unconventional myosin-Va (MYO5A).	[24]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Unconventional myosin-Va (MYO5A).	[25]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Unconventional myosin-Va (MYO5A).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Unconventional myosin-Va (MYO5A).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Unconventional myosin-Va (MYO5A).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Unconventional myosin-Va (MYO5A).	[30]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Unconventional myosin-Va (MYO5A).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Unconventional myosin-Va (MYO5A).	[34]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Unconventional myosin-Va (MYO5A).	[35]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Unconventional myosin-Va (MYO5A).	[36]

References

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