Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1C6J3K)

• DOT Name: Protein strawberry notch homolog 2 (SBNO2)
• Gene Name: SBNO2
• Related Disease:
  Alzheimer disease
  Autism spectrum disorder
  Autosomal recessive early-onset Parkinson disease 6
  Autosomal recessive juvenile Parkinson disease 2
  Brain neoplasm
  Carcinoma
  Carcinoma of esophagus
  Chagas disease
  Esophageal cancer
  Huntington disease
  Multiple sclerosis
  Neoplasm
  Neoplasm of esophagus
  Parkinson disease
  Pulmonary arterial hypertension
  Schizophrenia
  Squamous cell carcinoma
  Ankylosing spondylitis
  Asthma
  Crohn disease
  Inflammatory bowel disease
  Neuroblastoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: SBNO2_HUMAN
• Pfam ID: PF13872 ; PF13871
• Sequence:
  MLAVGPAMDRDYPQHEPPPAGSLLYSPPPLQSAMLHCPYWNTFSLPPYPAFSSDSRPFMS
  SASFLGSQPCPDTSYAPVATASSLPPKTCDFAQDSSYFEDFSNISIFSSSVDSLSDIVDT
  PDFLPADSLNQVSTIWDDNPAPSTHDKLFQLSRPFAGFEDFLPSHSTPLLVSYQEQSVQS
  QPEEEDEAEEEEAEELGHTETYADYVPSKSKIGKQHPDRVVETSTLSSVPPPDITYTLAL
  PSDSGALSALQLEAITYACQQHEVLLPSGQRAGFLIGDGAGVGKGRTVAGVILENHLRGR
  KKALWFSVSNDLKYDAERDLRDIEATGIAVHALSKIKYGDTTTSEGVLFATYSALIGESQ
  AGGQHRTRLRQILDWCGEAFEGVIVFDECHKAKNAGSTKMGKAVLDLQNKLPLARVVYAS
  ATGASEPRNMIYMSRLGIWGEGTPFRNFEEFLHAIEKRGVGAMEIVAMDMKVSGMYIARQ
  LSFSGVTFRIEEIPLAPAFECVYNRAALLWAEALNVFQQAADWIGLESRKSLWGQFWSAH
  QRFFKYLCIAAKVRRLVELAREELARDKCVVIGLQSTGEARTREVLGENDGHLNCFVSAA
  EGVFLSLIQKHFPSTKRKRDRGAGSKRKRRPRGRGAKAPRLACETAGVIRISDDSSTESD
  PGLDSDFNSSPESLVDDDVVIVDAVGLPSDDRGPLCLLQRDPHGPGVLERVERLKQDLLD
  KVRRLGRELPVNTLDELIDQLGGPQRVAEMTGRKGRVVSRPDGTVAFESRAEQGLSIDHV
  NLREKQRFMSGEKLVAIISEASSSGVSLQADRRVQNQRRRVHMTLELPWSADRAIQQFGR
  THRSNQVSAPEYVFLISELAGERRFASIVAKRLESLGALTHGDRRATESRDLSKYNFENK
  YGTRALHCVLTTILSQTENKVPVPQGYPGGVPTFFRDMKQGLLSVGIGGRESRNGCLDVE
  KDCSITKFLNRILGLEVHKQNALFQYFSDTFDHLIEMDKREGKYDMGILDLAPGIEEIYE
  ESQQVFLAPGHPQDGQVVFYKISVDRGLKWEDAFAKSLALTGPYDGFYLSYKVRGNKPSC
  LLAEQNRGQFFTVYKPNIGRQSQLEALDSLRRKFHRVTAEEAKEPWESGYALSLTHCSHS
  AWNRHCRLAQEGKDCLQGLRLRHHYMLCGALLRVWGRIAAVMADVSSSSYLQIVRLKTKD
  RKKQVGIKIPEGCVRRVLQELRLMDADVKRRQAPALGCPAPPAPRPLALPCGPGEVLDLT
  YSPPAEAFPPPPHFSFPAPLSLDAGPGVVPLGTPDAQADPAALAHQGCDINFKEVLEDML
  RSLHAGPPSEGALGEGAGAGGAAGGGPERQSVIQFSPPFPGAQAPL
• Function: Acts as a transcriptional coregulator, that can have both coactivator and corepressor functions. Inhibits the DCSTAMP-repressive activity of TAL1, hence enhancing the access of the transcription factor MITF to the DC-STAMP promoter in osteoclast. Plays a role in bone homeostasis; required as a positive regulator in TNFSF11//RANKL-mediated osteoclast fusion via a DCSTAMP-dependent pathway. May also be required in the regulation of osteoblast differentiation. Involved in the transcriptional corepression of NF-kappaB in macrophages. Plays a role as a regulator in the pro-inflammatory cascade.
• Tissue Specificity: Detected in macrophages. IL10 regulates expression in a STAT3-dependent way.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Autosomal recessive early-onset Parkinson disease 6	DISHVLD5	Strong	Biomarker	[3]
Autosomal recessive juvenile Parkinson disease 2	DISNSTD1	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[6]
Chagas disease	DIS8KNVF	Strong	Biomarker	[7]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[6]
Huntington disease	DISQPLA4	Strong	Biomarker	[8]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[6]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[11]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Biomarker	[12]
Schizophrenia	DISSRV2N	Strong	Biomarker	[13]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[14]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[15]
Asthma	DISW9QNS	Limited	Genetic Variation	[16]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[17]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[17]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[18]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[19]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[20]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[15]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[15]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[15]

6 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 Protein strawberry notch homolog 2 (SBNO2).	[21]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein strawberry notch homolog 2 (SBNO2).	[25]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Protein strawberry notch homolog 2 (SBNO2).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein strawberry notch homolog 2 (SBNO2).	[29]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein strawberry notch homolog 2 (SBNO2).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein strawberry notch homolog 2 (SBNO2).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein strawberry notch homolog 2 (SBNO2).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein strawberry notch homolog 2 (SBNO2).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein strawberry notch homolog 2 (SBNO2).	[24]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protein strawberry notch homolog 2 (SBNO2).	[26]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein strawberry notch homolog 2 (SBNO2).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein strawberry notch homolog 2 (SBNO2).	[31]

References

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• [5] Amplification of Cyclin L1 is associated with lymph node metastases in head and neck squamous cell carcinoma (HNSCC).Br J Cancer. 2005 Feb 28;92(4):770-4. doi: 10.1038/sj.bjc.6602400.
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• [11] The Essential Role of Drp1 and Its Regulation by S-Nitrosylation of Parkin in Dopaminergic Neurodegeneration: Implications for Parkinson's Disease.Antioxid Redox Signal. 2016 Oct 10;25(11):609-622. doi: 10.1089/ars.2016.6634. Epub 2016 Aug 8.
• [12] A novel S-nitrosocaptopril monohydrate for pulmonary arterial hypertension: H(2)O and -SNO intermolecular stabilization chemistry.Free Radic Biol Med. 2018 Dec;129:107-115. doi: 10.1016/j.freeradbiomed.2018.09.020. Epub 2018 Sep 15.
• [13] Construction and analysis of the protein-protein interaction networks for schizophrenia, bipolar disorder, and major depression.BMC Bioinformatics. 2011;12 Suppl 13(Suppl 13):S20. doi: 10.1186/1471-2105-12-S13-S20. Epub 2011 Nov 30.
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• [15] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
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• [18] A-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet.Biochim Biophys Acta. 2016 May;1864(5):609-21. doi: 10.1016/j.bbapap.2016.02.003. Epub 2016 Feb 5.
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• [21] 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.
• [22] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [23] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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• [25] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
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• [29] 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.
• [30] 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.
• [31] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.