Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNX3RL0)

• DOT Name: Protein strawberry notch homolog 1 (SBNO1)
• Synonyms: Monocyte protein 3; MOP-3
• Gene Name: SBNO1
• 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
  Knee osteoarthritis
  Neoplasm
  Neoplasm of esophagus
  Non-insulin dependent diabetes
  Parkinson disease
  Pulmonary arterial hypertension
  Schizophrenia
  Squamous cell carcinoma
  Venous thromboembolism
  Intellectual disability
  Neuroblastoma
  Non-small-cell lung cancer
  Pneumococcal infection
• UniProt ID: SBNO1_HUMAN
• Pfam ID: PF13872 ; PF13871
• Sequence:
  MVEPGQDLLLAALSESGISPNDLFDIDGGDAGLATPMPTPSVQQSVPLSALELGLETEAA
  VPVKQEPETVPTPALLNVRQQPPSTTTFVLNQINHLPPLGSTIVMTKTPPVTTNRQTITL
  TKFIQTTASTRPSVSAPTVRNAMTSAPSKDQVQLKDLLKNNSLNELMKLKPPANIAQPVA
  TAATDVSNGTVKKESSNKEGARMWINDMKMRSFSPTMKVPVVKEDDEPEEEDEEEMGHAE
  TYAEYMPIKLKIGLRHPDAVVETSSLSSVTPPDVWYKTSISEETIDNGWLSALQLEAITY
  AAQQHETFLPNGDRAGFLIGDGAGVGKGRTIAGIIYENYLLSRKRALWFSVSNDLKYDAE
  RDLRDIGAKNILVHSLNKFKYGKISSKHNGSVKKGVIFATYSSLIGESQSGGKYKTRLKQ
  LLHWCGDDFDGVIVFDECHKAKNLCPVGSSKPTKTGLAVLELQNKLPKARVVYASATGAS
  EPRNMAYMNRLGIWGEGTPFREFSDFIQAVERRGVGAMEIVAMDMKLRGMYIARQLSFTG
  VTFKIEEVLLSQSYVKMYNKAVKLWVIARERFQQAADLIDAEQRMKKSMWGQFWSAHQRF
  FKYLCIASKVKRVVQLAREEIKNGKCVVIGLQSTGEARTLEALEEGGGELNDFVSTAKGV
  LQSLIEKHFPAPDRKKLYSLLGIDLTAPSNNSSPRDSPCKENKIKKRKGEEITREAKKAR
  KVGGLTGSSSDDSGSESDASDNEESDYESSKNMSSGDDDDFNPFLDESNEDDENDPWLIR
  KDHKKNKEKKKKKSIDPDSIQSALLASGLGSKRPSFSSTPVISPAPNSTPANSNTNSNSS
  LITSQDAVERAQQMKKDLLDKLEKLAEDLPPNTLDELIDELGGPENVAEMTGRKGRVVSN
  DDGSISYESRSELDVPVEILNITEKQRFMDGDKNIAIISEAASSGISLQADRRAKNQRRR
  VHMTLELPWSADRAIQQFGRTHRSNQVTAPEYVFLISELAGEQRFASIVAKRLESLGALT
  HGDRRATESRDLSRFNFDNKYGRNALEIVMKSIVNLDSPMVSPPPDYPGEFFKDVRQGLI
  GVGLINVEDRSGILTLDKDYNNIGKFLNRILGMEVHQQNALFQYFADTLTAVVQNAKKNG
  RYDMGILDLGSGDEKVRKSDVKKFLTPGYSTSGHVELYTISVERGMSWEEATKIWAELTG
  PDDGFYLSLQIRNNKKTAILVKEVNPKKKLFLVYRPNTGKQLKLEIYADLKKKYKKVVSD
  DALMHWLDQYNSSADTCTHAYWRGNCKKASLGLVCEIGLRCRTYYVLCGSVLSVWTKVEG
  VLASVSGTNVKMQIVRLRTEDGQRIVGLIIPANCVSPLVNLLSTSDQSQQLAVQQKQLWQ
  QHHPQSITNLSNA

Molecular Interaction Atlas (MIA) of This DOT

23 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]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[11]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[12]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Biomarker	[13]
Schizophrenia	DISSRV2N	Strong	Biomarker	[14]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[15]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[16]
Intellectual disability	DISMBNXP	Limited	Biomarker	[17]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[19]
Pneumococcal infection	DIS6SXQD	Limited	Altered Expression	[20]

9 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 strawberry notch homolog 1 (SBNO1).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein strawberry notch homolog 1 (SBNO1).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein strawberry notch homolog 1 (SBNO1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein strawberry notch homolog 1 (SBNO1).	[24]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein strawberry notch homolog 1 (SBNO1).	[25]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Protein strawberry notch homolog 1 (SBNO1).	[26]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein strawberry notch homolog 1 (SBNO1).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein strawberry notch homolog 1 (SBNO1).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein strawberry notch homolog 1 (SBNO1).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein strawberry notch homolog 1 (SBNO1).	[29]

References

• [1] The roles of S-nitrosylation and S-glutathionylation in Alzheimer's disease.Methods Enzymol. 2019;626:499-538. doi: 10.1016/bs.mie.2019.08.004.
• [2] Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function.Mol Psychiatry. 2020 Aug;25(8):1835-1848. doi: 10.1038/s41380-018-0113-6. Epub 2018 Jul 9.
• [3] S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson's Disease Models.Cell Rep. 2017 Nov 21;21(8):2171-2182. doi: 10.1016/j.celrep.2017.10.068.
• [4] Anticonvulsant prophylaxis and steroid use in adults with metastatic brain tumors: summary of SNO and ASCO endorsement of the Congress of Neurological Surgeons guidelines.Neuro Oncol. 2019 Mar 18;21(4):424-427. doi: 10.1093/neuonc/noz034.
• [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.
• [6] A Comparison of the Toxicity of Mono, Bis, Tris and Tetrakis Phosphino Silver Complexes on SNO Esophageal Cancer Cells.Anticancer Agents Med Chem. 2018;18(3):394-400. doi: 10.2174/1871520617666170522123742.
• [7] Potential Utility of Protein Targets of Cysteine-S-Nitrosylation in Identifying Clinical Disease Status in Human Chagas Disease.Front Microbiol. 2019 Jan 15;9:3320. doi: 10.3389/fmicb.2018.03320. eCollection 2018.
• [8] S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington's disease.Antioxid Redox Signal. 2013 Oct 10;19(11):1173-84. doi: 10.1089/ars.2012.4928. Epub 2013 Jun 20.
• [9] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [10] The Role of Survivorship Care for Patients with Glioma.Semin Oncol Nurs. 2018 Dec;34(5):547-552. doi: 10.1016/j.soncn.2018.10.015. Epub 2018 Nov 13.
• [11] Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nat Genet. 2018 Apr;50(4):559-571. doi: 10.1038/s41588-018-0084-1. Epub 2018 Apr 9.
• [12] 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.
• [13] 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.
• [14] Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet. 2011 Jul 10;43(9):860-3. doi: 10.1038/ng.886.
• [15] SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus.Biochem Biophys Res Commun. 2001 Aug 24;286(3):559-65. doi: 10.1006/bbrc.2001.5428.
• [16] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [17] Genomic structural variants are linked with intellectual disability.J Neural Transm (Vienna). 2015 Sep;122(9):1289-301. doi: 10.1007/s00702-015-1366-8. Epub 2015 Jan 28.
• [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.
• [19] TERC identified as a probable target within the 3q26 amplicon that is detected frequently in non-small cell lung cancers.Clin Cancer Res. 2003 Oct 15;9(13):4705-13.
• [20] An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action.Nat Med. 2014 Aug;20(8):919-26. doi: 10.1038/nm.3599. Epub 2014 Jul 27.
• [21] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [22] 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.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [25] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [26] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [27] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [28] 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.
• [29] 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.
• [30] 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.