Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMS3D8W)

• DOT Name: Unconventional myosin-XVI (MYO16)
• Synonyms: Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 3; Unconventional myosin-16
• Gene Name: MYO16
• Related Disease:
  Alzheimer disease
  Autism spectrum disorder
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Intellectual disability
  Isolated congenital microcephaly
  Meningococcal disease
  Schizophrenia
  Nephropathy
  Type-1/2 diabetes
• UniProt ID: MYO16_HUMAN
• Pfam ID: PF12796 ; PF00063 ; PF15452 ; PF15439
• Sequence:
  MEIDQCLLESLPLGQRQRLVKRMRCEQIKAYYEREKAFQKQEGFLKRLKHAKNPKVHFNL
  TDMLQDAIIHHNDKEVLRLLKEGADPHTLVSSGGSLLHLCARYDNAFIAEILIDRGVNVN
  HQDEDFWTPMHIACACDNPDIVLLLVLAGANVLLQDVNGNIPLDYAVEGTESSSILLTYL
  DENGVDLTSLRQMKLQRPMSMLTDVKHFLSSGGNVNEKNDEGVTLLHMACASGYKEVVSL
  ILEHGGDLNIVDDQYWTPLHLAAKYGQTNLVKLLLMHQANPHLVNCNEEKASDIAASEFI
  EEMLLKAEIAWEEKMKEPLSASTLAQEEPYEEIIHDLPVLSSKLSPLVLPIAKQDSLLEK
  DIMFKDATKGLCKQQSQDSIPENPMMSGSTKPEQVKLMPPAPNDDLATLSELNDGSLLYE
  IQKRFGNNQIYTFIGDILLLVNPYKELPIYSSMVSQLYFSSSGKLCSSLPPHLFSCVERA
  FHQLFREQRPQCFILSGERGSGKSEASKQIIRHLTCRAGASRATLDSRFKHVVCILEAFG
  HAKTTLNDLSSCFIKYFELQFCERKQQLTGARIYTYLLEKSRLVSQPLGQSNFLIFYLLM
  DGLSAEEKYGLHLNNLCAHRYLNQTIQDDASTGERSLNREKLAVLKRALNVVGFSSLEVE
  NLFVILAAILHLGDIRFTALNEGNSAFVSDLQLLEQVAGMLQVSTDELASALTTDIQYFK
  GDMIIRRHTIQIAEFFRDLLAKSLYSRLFSFLVNTMNSCLHSQDEQKSMQTLDIGILDIF
  GFEEFQKNEFEQLCVNMTNEKMHHYINEVLFLHEQVECVQEGVTMETAYSPGNQNGVLDF
  FFQKPSGFLTLLDEESQMIWSVESNFPKKLQSLLESSNTNAVYSPMKDGNGNVALKDHGT
  AFTIMHYAGRVMYDVVGAIEKNKDSLSQNLLFVMKTSENVVINHLFQSKLSQTGSLVSAY
  PSFKFRGHKSALLSKKMTASSIIGENKNYLELSKLLKKKGTSTFLQRLERGDPVTIASQL
  RKSLMDIIGKLQKCTPHFIHCIRPNNSKLPDTFDNFYVSAQLQYIGVLEMVKIFRYGYPV
  RLSFSDFLSRYKPLADTFLREKKEQSAAERCRLVLQQCKLQGWQMGVRKVFLKYWHADQL
  NDLCLQLQRKIITCQKVIRGFLARQHLLQRISIRQQEVTSINSFLQNTEDMGLKTYDALV
  IQNASDIARENDRLRSEMNAPYHKEKLEVRNMQEEGSKRTDDKSGPRHFHPSSMSVCAAV
  DGLGQCLVGPSIWSPSLHSVFSMDDSSSLPSPRKQPPPKPKRDPNTRLSASYEAVSACLS
  AAREAANEALARPRPHSDDYSTMKKIPPRKPKRSPNTKLSGSYEEISGSRPGDARPAGAP
  GAAARVLTPGTPQCALPPAAPPGDEDDSEPVYIEMLGHAARPDSPDPGESVYEEMKCCLP
  DDGGPGAGSFLLHGASPPLLHRAPEDEAAGPPGDACDIPPPFPNLLPHRPPLLVFPPTPV
  TCSPASDESPLTPLEVKKLPVLETNLKYPVQPEGSSPLSPQYSKSQKGDGDRPASPGLAL
  FNGSGRASPPSTPPPPPPPPGPPPAPYRPCAHLAFPPEPAPVNAGKAGPSAEAPKVHPKP
  NSAPVAGPCSSFPKIPYSPVKATRADARKAGSSASPPAPYSPPSSRPLSSPLDELASLFN
  SGRSVLRKSAAGRKIREAEGFETNMNISSRDDPSTSEITSETQDRNANNHGIQLSNSLSS
  AITAENGNSISNGLPEEDGYSRLSISGTGTSTFQRHRDSHTTQVIHQLRLSENESVALQE
  LLDWRRKLCEEGQDWQQILHHAEPRVPPPPPCKKPSLLKKPEGASCNRLPSELWDTTI
• Function: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. May be involved in targeting of the catalytic subunit of protein phosphatase 1 during brain development. Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis.
• KEGG Pathway: Motor proteins (hsa04814)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[2]
Colon cancer	DISVC52G	Strong	Genetic Variation	[3]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[3]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[3]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[3]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[3]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[4]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[4]
Meningococcal disease	DISGDM2Z	Strong	Genetic Variation	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[6]
Nephropathy	DISXWP4P	moderate	Genetic Variation	[7]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[7]

3 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-XVI (MYO16).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Unconventional myosin-XVI (MYO16).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Unconventional myosin-XVI (MYO16).	[13]

4 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 Unconventional myosin-XVI (MYO16).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Unconventional myosin-XVI (MYO16).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Unconventional myosin-XVI (MYO16).	[11]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Unconventional myosin-XVI (MYO16).	[14]

References

• [1] Genome-wide analysis of genetic predisposition to Alzheimer's disease and related sex disparities.Alzheimers Res Ther. 2019 Jan 12;11(1):5. doi: 10.1186/s13195-018-0458-8.
• [2] Sex-specific association of a common variant of the XG gene with autism spectrum disorders.Am J Med Genet B Neuropsychiatr Genet. 2013 Oct;162B(7):742-50. doi: 10.1002/ajmg.b.32165.
• [3] Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas.Oncotarget. 2017 Oct 9;8(58):98623-98634. doi: 10.18632/oncotarget.21697. eCollection 2017 Nov 17.
• [4] Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment.PLoS One. 2015 Apr 22;10(4):e0123106. doi: 10.1371/journal.pone.0123106. eCollection 2015.
• [5] Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease.Nat Genet. 2010 Sep;42(9):772-6. doi: 10.1038/ng.640. Epub 2010 Aug 8.
• [6] Fine mapping on chromosome 13q32-34 and brain expression analysis implicates MYO16 in schizophrenia.Neuropsychopharmacology. 2014 Mar;39(4):934-43. doi: 10.1038/npp.2013.293. Epub 2013 Oct 21.
• [7] An intergenic region on chromosome 13q33.3 is associated with the susceptibility to kidney disease in type 1 and 2 diabetes.Kidney Int. 2011 Jul;80(1):105-11. doi: 10.1038/ki.2011.64. Epub 2011 Mar 16.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] 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.
• [10] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.