Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9VWV18)

DOT Name Protein SON (SON)
Synonyms Bax antagonist selected in saccharomyces 1; BASS1; Negative regulatory element-binding protein; NRE-binding protein; Protein DBP-5; SON3
Gene Name SON
Related Disease
ZTTK syndrome ( )
Cystic kidney disease ( )
Hepatitis ( )
Hepatitis A virus infection ( )
Influenza ( )
Intellectual disability ( )
leukaemia ( )
Leukemia ( )
Medulloblastoma ( )
Movement disorder ( )
Neoplasm ( )
Advanced cancer ( )
Psoriasis ( )
UniProt ID
SON_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7CIQ; 7CIR; 7CIS; 7DYN
Pfam ID
PF14709 ; PF01585 ; PF17069
Sequence
MATNIEQIFRSFVVSKFREIQQELSSGRNEGQLNGETNTPIEGNQAGDAAASARSLPNEE
IVQKIEEVLSGVLDTELRYKPDLKEGSRKSRCVSVQTDPTDEIPTKKSKKHKKHKNKKKK
KKKEKEKKYKRQPEESESKTKSHDDGNIDLESDSFLKFDSEPSAVALELPTRAFGPSETN
ESPAVVLEPPVVSMEVSEPHILETLKPATKTAELSVVSTSVISEQSEQSVAVMPEPSMTK
ILDSFAAAPVPTTTLVLKSSEPVVTMSVEYQMKSVLKSVESTSPEPSKIMLVEPPVAKVL
EPSETLVVSSETPTEVYPEPSTSTTMDFPESSAIEALRLPEQPVDVPSEIADSSMTRPQE
LPELPKTTALELQESSVASAMELPGPPATSMPELQGPPVTPVLELPGPSATPVPELPGPL
STPVPELPGPPATAVPELPGPSVTPVPQLSQELPGLPAPSMGLEPPQEVPEPPVMAQELP
GLPLVTAAVELPEQPAVTVAMELTEQPVTTTELEQPVGMTTVEHPGHPEVTTATGLLGQP
EATMVLELPGQPVATTALELPGQPSVTGVPELPGLPSATRALELSGQPVATGALELPGPL
MAAGALEFSGQSGAAGALELLGQPLATGVLELPGQPGAPELPGQPVATVALEISVQSVVT
TSELSTMTVSQSLEVPSTTALESYNTVAQELPTTLVGETSVTVGVDPLMAPESHILASNT
METHILASNTMDSQMLASNTMDSQMLASNTMDSQMLASSTMDSQMLATSSMDSQMLATSS
MDSQMLATSTMDSQMLATSSMDSQMLATSSMDSQMLATSSMDSQMLATSSMDSQMLATST
MDSQMLATSTMDSQMLATSSMDSQMLASGTMDSQMLASGTMDAQMLASGTMDAQMLASST
QDSAMLGSKSPDPYRLAQDPYRLAQDPYRLGHDPYRLGHDAYRLGQDPYRLGHDPYRLTP
DPYRMSPRPYRIAPRSYRIAPRPYRLAPRPLMLASRRSMMMSYAAERSMMSSYERSMMSY
ERSMMSPMAERSMMSAYERSMMSAYERSMMSPMAERSMMSAYERSMMSAYERSMMSPMAD
RSMMSMGADRSMMSSYSAADRSMMSSYSAADRSMMSSYTADRSMMSMAADSYTDSYTDTY
TEAYMVPPLPPEEPPTMPPLPPEEPPMTPPLPPEEPPEGPALPTEQSALTAENTWPTEVP
SSPSEESVSQPEPPVSQSEISEPSAVPTDYSVSASDPSVLVSEAAVTVPEPPPEPESSIT
LTPVESAVVAEEHEVVPERPVTCMVSETPAMSAEPTVLASEPPVMSETAETFDSMRASGH
VASEVSTSLLVPAVTTPVLAESILEPPAMAAPESSAMAVLESSAVTVLESSTVTVLESST
VTVLEPSVVTVPEPPVVAEPDYVTIPVPVVSALEPSVPVLEPAVSVLQPSMIVSEPSVSV
QESTVTVSEPAVTVSEQTQVIPTEVAIESTPMILESSIMSSHVMKGINLSSGDQNLAPEI
GMQEIALHSGEEPHAEEHLKGDFYESEHGINIDLNINNHLIAKEMEHNTVCAAGTSPVGE
IGEEKILPTSETKQRTVLDTYPGVSEADAGETLSSTGPFALEPDATGTSKGIEFTTASTL
SLVNKYDVDLSLTTQDTEHDMVISTSPSGGSEADIEGPLPAKDIHLDLPSNNNLVSKDTE
EPLPVKESDQTLAALLSPKESSGGEKEVPPPPKETLPDSGFSANIEDINEADLVRPLLPK
DMERLTSLRAGIEGPLLASDVGRDRSAASPVVSSMPERASESSSEEKDDYEIFVKVKDTH
EKSKKNKNRDKGEKEKKRDSSLRSRSKRSKSSEHKSRKRTSESRSRARKRSSKSKSHRSQ
TRSRSRSRRRRRSSRSRSKSRGRRSVSKEKRKRSPKHRSKSRERKRKRSSSRDNRKTVRA
RSRTPSRRSRSHTPSRRRRSRSVGRRRSFSISPSRRSRTPSRRSRTPSRRSRTPSRRSRT
PSRRSRTPSRRSRTPSRRRRSRSVVRRRSFSISPVRLRRSRTPLRRRFSRSPIRRKRSRS
SERGRSPKRLTDLDKAQLLEIAKANAAAMCAKAGVPLPPNLKPAPPPTIEEKVAKKSGGA
TIEELTEKCKQIAQSKEDDDVIVNKPHVSDEEEEEPPFYHHPFKLSEPKPIFFNLNIAAA
KPTPPKSQVTLTKEFPVSSGSQHRKKEADSVYGEWVPVEKNGEENKDDDNVFSSNLPSEP
VDISTAMSERALAQKRLSENAFDLEAMSMLNRAQERIDAWAQLNSIPGQFTGSTGVQVLT
QEQLANTGAQAWIKKDQFLRAAPVTGGMGAVLMRKMGWREGEGLGKNKEGNKEPILVDFK
TDRKGLVAVGERAQKRSGNFSAAMKDLSGKHPVSALMEICNKRRWQPPEFLLVHDSGPDH
RKHFLFRVLRNGALTRPNCMFFLNRY
Function
RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1.
Tissue Specificity Widely expressed, with the higher expression seen in leukocyte and heart.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
ZTTK syndrome DISJ2N14 Definitive Autosomal dominant [1]
Cystic kidney disease DISRT1LM Strong Genetic Variation [2]
Hepatitis DISXXX35 Strong Biomarker [3]
Hepatitis A virus infection DISUMFQV Strong Biomarker [3]
Influenza DIS3PNU3 Strong Biomarker [4]
Intellectual disability DISMBNXP Strong Genetic Variation [5]
leukaemia DISS7D1V Strong Altered Expression [6]
Leukemia DISNAKFL Strong Altered Expression [6]
Medulloblastoma DISZD2ZL Strong Biomarker [7]
Movement disorder DISOJJ2D Strong Genetic Variation [5]
Neoplasm DISZKGEW Disputed Biomarker [8]
Advanced cancer DISAT1Z9 Limited Biomarker [9]
Psoriasis DIS59VMN Limited Genetic Variation [10]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Protein SON (SON) increases the response to substance of Arsenic trioxide. [27]
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21 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 Protein SON (SON). [11]
Ciclosporin DMAZJFX Approved Ciclosporin affects the expression of Protein SON (SON). [12]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Protein SON (SON). [13]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Protein SON (SON). [12]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein SON (SON). [14]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Protein SON (SON). [15]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Protein SON (SON). [17]
Selenium DM25CGV Approved Selenium decreases the expression of Protein SON (SON). [18]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Protein SON (SON). [14]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Protein SON (SON). [19]
Cidofovir DMA13GD Approved Cidofovir decreases the expression of Protein SON (SON). [12]
Ifosfamide DMCT3I8 Approved Ifosfamide decreases the expression of Protein SON (SON). [12]
Clodronate DM9Y6X7 Approved Clodronate decreases the expression of Protein SON (SON). [12]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Protein SON (SON). [20]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of Protein SON (SON). [13]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Protein SON (SON). [18]
Afimoxifene DMFORDT Phase 2 Afimoxifene decreases the expression of Protein SON (SON). [14]
ACYLINE DM9GRTK Phase 2 ACYLINE increases the expression of Protein SON (SON). [21]
UNC0379 DMD1E4J Preclinical UNC0379 decreases the expression of Protein SON (SON). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Protein SON (SON). [24]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Protein SON (SON). [25]
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⏷ Show the Full List of 21 Drug(s)
5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Quercetin DM3NC4M Approved Quercetin affects the phosphorylation of Protein SON (SON). [16]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Protein SON (SON). [22]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Protein SON (SON). [16]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Protein SON (SON). [16]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the phosphorylation of Protein SON (SON). [26]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renalphenotypes.Kidney Int. 2019 Jun;95(6):1494-1504. doi: 10.1016/j.kint.2019.01.025. Epub 2019 Mar 15.
3 The role of SON in splicing, development, and disease.Wiley Interdiscip Rev RNA. 2014 Sep-Oct;5(5):637-46. doi: 10.1002/wrna.1235. Epub 2014 Apr 30.
4 Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication.Nature. 2010 Feb 11;463(7282):818-22. doi: 10.1038/nature08760. Epub 2010 Jan 17.
5 De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome. Am J Hum Genet. 2016 Sep 1;99(3):711-719. doi: 10.1016/j.ajhg.2016.06.029. Epub 2016 Aug 18.
6 SON and Its Alternatively Spliced Isoforms Control MLL Complex-Mediated H3K4me3 and Transcription of Leukemia-Associated Genes.Mol Cell. 2016 Mar 17;61(6):859-73. doi: 10.1016/j.molcel.2016.02.024.
7 Mutated SON putatively causes a cancer syndrome comprising high-risk medulloblastoma combined with caf-au-lait spots.Fam Cancer. 2019 Jul;18(3):353-358. doi: 10.1007/s10689-019-00121-z.
8 Noninvasive imaging of human telomerase reverse transcriptase (hTERT) messenger RNA with 99mTc-radiolabeled antisense probes in malignant tumors.J Nucl Med. 2007 Dec;48(12):2028-36. doi: 10.2967/jnumed.107.042622. Epub 2007 Nov 15.
9 Translation termination depends on the sequential ribosomal entry of eRF1 and eRF3.Nucleic Acids Res. 2019 May 21;47(9):4798-4813. doi: 10.1093/nar/gkz177.
10 Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis.Nat Commun. 2015 Apr 9;6:6793. doi: 10.1038/ncomms7793.
11 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
12 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
13 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
14 Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
15 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.
16 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.
17 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
18 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.
19 Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
20 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
21 Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
22 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.
23 Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
24 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
25 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.
26 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
27 The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.