Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTR5311)

• DOT Name: Double-stranded RNA-binding protein Staufen homolog 1 (STAU1)
• Gene Name: STAU1
• Related Disease:
  Colorectal carcinoma
  Gastric cancer
  Hepatitis C virus infection
  Major depressive disorder
  Neoplasm
  Schizophrenia
  Spinocerebellar ataxia type 2
  Stomach cancer
  Ebola virus infection
  Enterovirus infection
  Neuroblastoma
  Obesity
  X-linked congenital generalized hypertrichosis
• UniProt ID: STAU1_HUMAN
• PDB ID: 4DKK; 6HTU; 6SDW; 6SDY
• Pfam ID: PF00035 ; PF16482
• Sequence:
  MSQVQVQVQNPSAALSGSQILNKNQSLLSQPLMSIPSTTSSLPSENAGRPIQNSALPSAS
  ITSTSAAAESITPTVELNALCMKLGKKPMYKPVDPYSRMQSTYNYNMRGGAYPPRYFYPF
  PVPPLLYQVELSVGGQQFNGKGKTRQAAKHDAAAKALRILQNEPLPERLEVNGRESEEEN
  LNKSEISQVFEIALKRNLPVNFEVARESGPPHMKNFVTKVSVGEFVGEGEGKSKKISKKN
  AAIAVLEELKKLPPLPAVERVKPRIKKKTKPIVKPQTSPEYGQGINPISRLAQIQQAKKE
  KEPEYTLLTERGLPRRREFVMQVKVGNHTAEGTGTNKKVAKRNAAENMLEILGFKVPQAQ
  PTKPALKSEEKTPIKKPGDGRKVTFFEPGSGDENGTSNKEDEFRMPYLSHQQLPAGILPM
  VPEVAQAVGVSQGHHTKDFTRAAPNPAKATVTAMIARELLYGGTSPTAETILKNNISSGH
  VPHGPLTRPSEQLDYLSRVQGFQVEYKDFPKNNKNEFVSLINCSSQPPLISHGIGKDVES
  CHDMAALNILKLLSELDQQSTEMPRTGNGPMSVCGRC
• Function: Binds double-stranded RNA (regardless of the sequence) and tubulin. May play a role in specific positioning of mRNAs at given sites in the cell by cross-linking cytoskeletal and RNA components, and in stimulating their translation at the site.; (Microbial infection) Plays a role in virus particles production of many viruses including of HIV-1, HERV-K, ebola virus and influenza virus. Acts by interacting with various viral proteins involved in particle budding process.
• Tissue Specificity: Widely expressed. Expressed in brain, pancreas, heart, skeletal muscles, liver, lung, kidney and placenta.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[3]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[5]
Spinocerebellar ataxia type 2	DISF7WDI	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[7]
Enterovirus infection	DISH2UDP	Limited	Biomarker	[8]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[9]
Obesity	DIS47Y1K	Limited	Genetic Variation	[10]
X-linked congenital generalized hypertrichosis	DISVL46B	Limited	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[20]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Double-stranded RNA-binding protein Staufen homolog 1 (STAU1).	[18]

References

• [1] SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization.Nat Commun. 2016 Dec 22;7:13875. doi: 10.1038/ncomms13875.
• [2] E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis.Cell Death Dis. 2017 Jun 1;8(6):e2837. doi: 10.1038/cddis.2017.205.
• [3] Staufen1 promotes HCV replication by inhibiting protein kinase R and transporting viral RNA to the site of translation and replication in the cells.Nucleic Acids Res. 2016 Jun 20;44(11):5271-87. doi: 10.1093/nar/gkw312. Epub 2016 Apr 22.
• [4] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [5] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [6] Staufen1 links RNA stress granules and autophagy in a model of neurodegeneration.Nat Commun. 2018 Sep 7;9(1):3648. doi: 10.1038/s41467-018-06041-3.
• [7] Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis.mBio. 2018 Oct 9;9(5):e01771-18. doi: 10.1128/mBio.01771-18.
• [8] Staufen1 Protein Participates Positively in the Viral RNA Replication of Enterovirus 71.Viruses. 2019 Feb 8;11(2):142. doi: 10.3390/v11020142.
• [9] Lin28B and miR-142-3p regulate neuronal differentiation by modulating Staufen1 expression.Cell Death Differ. 2018 Feb;25(2):432-443. doi: 10.1038/cdd.2017.182. Epub 2017 Nov 3.
• [10] Regulated expression of Gemin5, Xrn1, Cpeb and Stau1 in the uterus and ovaries after superovulation and the effect of exogenous estradiol and leptin in rodents.Mol Biol Rep. 2019 Apr;46(2):2533-2540. doi: 10.1007/s11033-019-04606-z. Epub 2019 Jan 28.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] 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.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [17] 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.
• [18] 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.
• [19] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [20] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.