Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT80PO4Q)

• DOT Name: Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 (NYAP2)
• Gene Name: NYAP2
• UniProt ID: NYAP2_HUMAN
• Pfam ID: PF15452 ; PF15439
• Sequence:
  MISSKMMSSNPEEDPLDTFLQYIEDMGMKAYDGLVIQNASDIARENDRLRNETNLAYLKE
  KNEKRRRQEEAIKRIGGEVGRGHEGSYVGKHFRMGFMTMPAPQDRLPHPCSSGFSVRSQS
  LHSVGGTDDDSSCGSRRQPPPKPKRDPSTKLSTSSETVSSTAASKSGKTPERTEASAKPR
  PHSDEYSKKIPPPKPKRNPNTQLSTSFDETYIKKHGPRRTSLPRDSSLSQMGSPAGDPEE
  EEPVYIEMVGNILRDFRKEDDDQSEAVYEEMKYPIFDDLGQDAKCDFDHHSCSSQCATPT
  VPDLDFAKASVPCPPKGLLCDIPPPFPNLLSHRPPLLVFPPAPVHCSPNSDESPLTPLEV
  TKLPVLENVSYMKQPAGASPSTLPSHVPGHAKLEKEQAAALGPASATPALSSSPPPPSTL
  YRTQSPHGYPKSHSTSPSPVSMGRSLTPLSLKRPPPYDAVHSGSLSRSSPSVPHSTPRPV
  SQDGAKMVNAAVNTYGAAPGGSRSRTPTSPLEELTSLFSSGRSLLRKSSSGRRSKEPAEK
  STEELKVRSHSTEPLPKLDNKERGHHGASSSREPVKAQEWDGTPGTPVVTSRLGRCSVSP
  TLLAGNHSSEPKVSCKLGRSASTSGVPPPSVTPLRQSSDLQQSQVPSSLANRD
• Function: Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis.

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 Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 (NYAP2).	[1]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 (NYAP2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 (NYAP2).	[3]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 (NYAP2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 (NYAP2).	[5]

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] 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.
• [3] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [4] 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.
• [5] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.