Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA3ZP22)

• DOT Name: Unconventional myosin-XVB (MYO15B)
• Synonyms: Myosin XVBP; Unconventional myosin-15B
• Gene Name: MYO15B
• UniProt ID: MY15B_HUMAN
• PDB ID: 2DLP
• Pfam ID: PF00373 ; PF00063 ; PF00784 ; PF07653
• Sequence:
  MGRNQRKAPQRLERPGRPASGEQESGSASADGAPSRERRSDRGQADRAKPAAEPATAGGQ
  GTPGGRRKPTAEGNGGCRRPGAGLSPKAQERQSNAQRQGRGPRGGRGGRLEEGSLSGGEE
  LGGRRRRKRKDKGPSARRGRRTPRSLNGDTSGGDGGSSCPDSETREAQESGSQRGTAREL
  RPTPEPTDMGSEGTKTGPESALEPSSDGLDSDWPHADTRGREGSSGTGPLGASEHSGGDS
  DSSPLGTGPGRGSRAAMASRTFEDSSRAPRDTGPAKDASDNRAQRGAEPETMQASTARAP
  RHQVGKAVGQVPAAAGEGEAGAAAGAGPEDPAPLAALLVVRRLLARPPPGAASQAVGPRR
  AGLKERLLSVARALGLLRWLRRRLRLRRRPPEGEGQGTGPRASEGWGRRKPDEGRGHGRG
  SKGRGRGKADEGRGHERGDEGRGRGKADEGRGHERGYEGRGCGKADEGRGHERGDEGRDH
  QRGYEGWGREPGLRHRLALRLAGLAGLGGMPRASPGGRSPQVPTSPVPGDPFDQEDETPD
  PKFAVVFPRIHRAGRASSSRSSEEASADAPTGEGRGWPRAGVGGHSEGCRTSGEGVSGLR
  RGSLLAPTAPDGPSLDESGSSSEAELETLNDEPPVRWAQGSGPHEGPRLGAAVLLPRLSL
  ETRLQQEGDPGLRGSLRELWEPEDEDEAVLERDLELSLRPGLEAPPFPGAKGRSLGDGLE
  DMEDLARLRLVCDSSVLLCLKKRFHLGRIYTFGGPVLLVLNPHRSLPLFSPEVQASYHPR
  KALSTTPHIFAIVASAYDLAQNTGQDPCILLCSSHCSGHSGSGKTEAAKKIMQFLSSLEQ
  DQTGNRECQVEDMLPILSSFGHAKTILNANASRFGQVFCLYLQQGVIVGASVSHYLLETS
  RVVFQAQAERSFHVFYKLLAGLDSIERERLSLQGPETYYYLNQGQACRLQGKEDAQDFEG
  LLKALQGLGLCPEELNAVWAVLAAILQLGNICFSSSERESQEVAAVSSWAEIHTAARLLR
  VPPECLEGAVTRRVTETPYGQVSRSLPVESAFDARDALAKALYSRLFHRLLRRTNARLAP
  PGEGGSIGTVTVVDAYGFEALRVNGLEQLCNNLASERLQLFSSQMLLAQEEEECRRELLS
  WVPVPQPPRESCLDLLVDQPHSLLSILDAQTWLSQATDHTFLQKSHYHHGDHPSYAKPRL
  PLPVFTVRHYAGTVTYQVHKFLNRNRDQLDPAVVEMLGQSQLQLVGSLFQEAEPQSRGGR
  GRPTLASRFQQALEDLIARLGRSHVYFIQCLTPNPGKLPGLFDVGHVTEQLHQAAILEAV
  GTRSANFPVRVPFEAFLASFQALGSEGQEDLSDREKCGAVLSQVLGAESPLYHLGATKVL
  LQEQGWQRLEELRDQQRSQALVDLHRSFHTCISRQRVLPRMQARMRGFQARKRYLRRRAA
  LGQLNTILLVAQPLLQRRQRLQLGRWQGWHSSERALERVPSMELGRLEIPAELAVMLKTA
  ESHRDALAGSITECLPPEVPARPSLTLPADIDLFPFSSFVAIGFQEPSLPRPGQPLAKPL
  TQLDGDNPQRALDINKVMLRLLGDGSLESWQRQIMGAYLVRQGQCRPGLRNELFSQLVAQ
  LWQNPDEQQSQRGWALMAVLLSAFPPLPVLQKPLLKFVSDQAPRGMAALCQHKLLGALEQ
  SQLASGATRAHPPTQLEWLAGWRRGRMALDVFTFSEECYSAEVESWTTGEQLAGWILQSR
  GLEAPPRGWSVSLHSRDAWQDLAGCDFVLDLISQTEDLGDPARPRSYPITPLGSAEAIPL
  APGIQAPSLPPGPPPGPAPTLPSRDHTGEVQRSGSLDGFLDQIFQPVISSGLSDLEQSWA
  LSSRMKGGGAIGPTQQGYPMVYPGMIQMPAYQPGMVPAPMPMMPAMGTVPAMPAMVVPPQ
  PPLPSLDAGQLAVQQQNFIQQQALILAQQMTAQAMSLSLEQQMQQRQQQARASEAASQAS
  PSAVTSKPRKPPTPPEKPQRDLGSEGGCLRETSEEAEDRPYQPKSFQQKRNYFQRMGQPQ
  ITVRTMKPPAKVHIPQGEAQEEEEEEEEEEEQEEQEVETRAVPSPPPPPIVKKPLKQGGA
  KAPKEAEAEPAKETAAKGHGQGPAQGRGTVVRSSDSKPKRPQPSREIGNIIRMYQSRPGP
  VPVPVQPSRPPKAFLRKIDPKDEALAKLGINGAHSSPPMLSPSPGKGPPPAVAPRPKAPL
  QLGPSSSIKEKQGPLLDLFGQKLPIAHTPPPPPAPPLPLPEDPGTLSAERRCLTQPVEDQ
  GVSTQLLAPSGSVCFSYTGTPWKLFLRKEVFYPRENFSHPYYLRLLCEQILRDTFSESCI
  RISQNERRKMKDLLGGLEVDLDSLTTTEDSVKKRIVVAARDNWANYFSRFFPVSGESGSD
  VQLLAVSHRGLRLLKVTQGPGLRPDQLKILCSYSFAEVLGVECRGGSTLELSLKSEQLVL
  HTARARAIEALVELFLNELKKDSGYVIALRSYITDNCSLLSFHRGDLIKLLPVATLEPGW
  QFGSAGGRSGLFPADIVQPAAAPDFSFSKEQRSGWHKGQLSNGEPGLARWDRASERPAHP
  WSQAHSDDSEATSLSSVAYAFLPDSHSYTMQEFARRYFRRSQALLGQTDGGAAGKDTDSL
  VQYTKAPIQESLLSLSDDVSKLAVASFLALMRFMGDQSKPRGKDEMDLLYELLKLCQQEK
  LRDEIYCQVIKQVTGHPRPEHCTRGWSFLSLLTGFFPPSTRLMPYLTKFLQDSGPSQELA
  RSSQEHLQRTVKYGGRRRMPPPGEMKAFLKGQAIRLLLIHLPGGVDYRTNIQTFTVAAEV
  QEELCRQMGITEPQEVQEFALFLIKEKSQLVRPLQPAEYLNSVVVDQDVSLHSRRLHWET
  PLHFDNSTYISTHYSQVLWDYLQGKLPVSAKADAQLARLAALQHLSKANRNTPSGQDLLA
  YVPKQLQRQVNTASIKNLMGQELRRLEGHSPQEAQISFIEAMSQLPLFGYTVYGVLRVSM
  QALSGPTLLGLNRQHLILMDPSSQSLYCRIALKSLQRLHLLSPLEEKGPPGLEVNYGSAD
  NPQTIWFELPQAQELLYTTVFLIDSSASCTEWPSIN
• Tissue Specificity: Detected in brain, stomach and kidney.
• KEGG Pathway: Motor proteins (hsa04814)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Unconventional myosin-XVB (MYO15B).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Unconventional myosin-XVB (MYO15B).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Unconventional myosin-XVB (MYO15B).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Unconventional myosin-XVB (MYO15B).	[8]

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-XVB (MYO15B).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Unconventional myosin-XVB (MYO15B).	[3]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Unconventional myosin-XVB (MYO15B).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Unconventional myosin-XVB (MYO15B).	[6]

References

• [1] 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.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [5] 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.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] 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.
• [8] 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.