Details of Drug Off-Target (DOT)

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

• DOT Name: Double-stranded RNA-binding protein Staufen homolog 2 (STAU2)
• Gene Name: STAU2
• Related Disease: Microphthalmia
• UniProt ID: STAU2_HUMAN
• Pfam ID: PF00035 ; PF16482
• Sequence:
  MANPKEKTAMCLVNELARFNRVQPQYKLLNERGPAHSKMFSVQLSLGEQTWESEGSSIKK
  AQQAVANKALTESTLPKPVQKPPKSNVNNNPGSITPTVELNGLAMKRGEPAIYRPLDPKP
  FPNYRANYNFRGMYNQRYHCPVPKIFYVQLTVGNNEFFGEGKTRQAARHNAAMKALQALQ
  NEPIPERSPQNGESGKDVDDDKDANKSEISLVFEIALKRNMPVSFEVIKESGPPHMKSFV
  TRVSVGEFSAEGEGNSKKLSKKRAATTVLQELKKLPPLPVVEKPKLFFKKRPKTIVKAGP
  EYGQGMNPISRLAQIQQAKKEKEPDYVLLSERGMPRRREFVMQVKVGNEVATGTGPNKKI
  AKKNAAEAMLLQLGYKASTNLQDQLEKTGENKGWSGPKPGFPEPTNNTPKGILHLSPDVY
  QEMEASRHKVISGTTLGYLSPKDMNQPSSSFFSISPTSNSSATIARELLMNGTSSTAEAI
  GLKGSSPTPPCSPVQPSKQLEYLARIQGFQAALSALKQFSEQGLDPIDGAMNIEKGSLEK
  QAKHLREKADNNQAPPGSIAQDCKKSNSAV
• Function: RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microphthalmia	DISGEBES	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[12]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[13]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Double-stranded RNA-binding protein Staufen homolog 2 (STAU2).	[9]

References

• [1] The double-stranded RNA-binding protein Staufen 2 regulates eye size.Mol Cell Neurosci. 2012 Nov;51(3-4):101-11. doi: 10.1016/j.mcn.2012.08.008. Epub 2012 Aug 24.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [14] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.