Details of Drug Off-Target (DOT)

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

• DOT Name: Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP)
• Synonyms: hnRNP Q; Glycine- and tyrosine-rich RNA-binding protein; GRY-RBP; NS1-associated protein 1; Synaptotagmin-binding, cytoplasmic RNA-interacting protein
• Gene Name: SYNCRIP
• Related Disease:
  Acute undifferentiated leukemia
  Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1
  Myeloid leukaemia
  Spinal muscular atrophy
  Frontotemporal dementia
  Leukemia
  Neuroblastoma
• UniProt ID: HNRPQ_HUMAN
• PDB ID: 2DGU; 2MXT; 2NBB; 6KOR
• Pfam ID: PF18360 ; PF00076
• Sequence:
  MATEHVNGNGTEEPMDTTSAVIHSENFQTLLDAGLPQKVAEKLDEIYVAGLVAHSDLDER
  AIEALKEFNEDGALAVLQQFKDSDLSHVQNKSAFLCGVMKTYRQREKQGTKVADSSKGPD
  EAKIKALLERTGYTLDVTTGQRKYGGPPPDSVYSGQQPSVGTEIFVGKIPRDLFEDELVP
  LFEKAGPIWDLRLMMDPLTGLNRGYAFVTFCTKEAAQEAVKLYNNHEIRSGKHIGVCISV
  ANNRLFVGSIPKSKTKEQILEEFSKVTEGLTDVILYHQPDDKKKNRGFCFLEYEDHKTAA
  QARRRLMSGKVKVWGNVGTVEWADPIEDPDPEVMAKVKVLFVRNLANTVTEEILEKAFSQ
  FGKLERVKKLKDYAFIHFDERDGAVKAMEEMNGKDLEGENIEIVFAKPPDQKRKERKAQR
  QAAKNQMYDDYYYYGPPHMPPPTRGRGRGGRGGYGYPPDYYGYEDYYDYYGYDYHNYRGG
  YEDPYYGYEDFQVGARGRGGRGARGAAPSRGRGAAPPRGRAGYSQRGGPGSARGVRGARG
  GAQQQRGRGVRGARGGRGGNVGGKRKADGYNQPDSKRRQTNNQNWGSQPIAQQPLQGGDH
  SGNYGYKSENQEFYQDTFGQQWK
• Function: Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 3 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation; seems not to be essential for GAIT complex function.
• Tissue Specificity: Ubiquitously expressed. Detected in heart, brain, pancreas, placenta, spleen, lung, liver, skeletal muscle, kidney, thymus, prostate, uterus, small intestine, colon, peripheral blood and testis.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute undifferentiated leukemia	DISJ4SSG	Strong	Biomarker	[1]
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1	DISBHBD6	Strong	Biomarker	[2]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[1]
Spinal muscular atrophy	DISTLKOB	Strong	Altered Expression	[3]
Frontotemporal dementia	DISKYHXL	moderate	Biomarker	[4]
Leukemia	DISNAKFL	Limited	Therapeutic	[1]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[5]

29 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 Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[12]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[17]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[18]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[19]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[20]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[21]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[22]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[23]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[18]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[29]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[30]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[31]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate affects the localization of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN affects the localization of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Heterogeneous nuclear ribonucleoprotein Q (SYNCRIP).	[28]

References

• [1] Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells.Nat Genet. 2017 Jun;49(6):866-875. doi: 10.1038/ng.3854. Epub 2017 Apr 24.
• [2] Tear Fluid Protein Changes in Dry Eye Syndrome Associated with Rheumatoid Arthritis: A Proteomic Approach.Ocul Surf. 2017 Jan;15(1):112-129. doi: 10.1016/j.jtos.2016.09.005. Epub 2016 Oct 24.
• [3] Key role of SMN/SYNCRIP and RNA-Motif 7 in spinal muscular atrophy: RNA-Seq and motif analysis of human motor neurons.Brain. 2019 Feb 1;142(2):276-294. doi: 10.1093/brain/awy330.
• [4] Heterogeneous nuclear ribonucleoproteins R and Q accumulate in pathological inclusions in FTLD-FUS.Acta Neuropathol Commun. 2019 Feb 12;7(1):18. doi: 10.1186/s40478-019-0673-y.
• [5] Systematic Analysis of Gene Expression Profiles Controlled by hnRNP Q and hnRNP R, Two Closely Related Human RNA Binding Proteins Implicated in mRNA Processing Mechanisms.Front Mol Biosci. 2018 Aug 30;5:79. doi: 10.3389/fmolb.2018.00079. eCollection 2018.
• [6] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [7] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [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] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [17] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [21] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [22] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [23] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [24] Human hnRNP Q re-localizes to cytoplasmic granules upon PMA, thapsigargin, arsenite and heat-shock treatments. Exp Cell Res. 2009 Apr 1;315(6):968-80. doi: 10.1016/j.yexcr.2009.01.012. Epub 2009 Feb 10.
• [25] 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.
• [26] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [27] 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.
• [28] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [29] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [30] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [31] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [32] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.