Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIVMQ2S)

• DOT Name: Beta-2-syntrophin (SNTB2)
• Synonyms: 59 kDa dystrophin-associated protein A1 basic component 2; Syntrophin-3; SNT3; Syntrophin-like; SNTL
• Gene Name: SNTB2
• Related Disease: Metabolic disorder
• UniProt ID: SNTB2_HUMAN
• PDB ID: 2VRF
• Pfam ID: PF00595 ; PF00169 ; PF18012
• Sequence:
  MRVAAATAAAGAGPAMAVWTRATKAGLVELLLRERWVRVVAELSGESLSLTGDAAAAELE
  PALGPAAAAFNGLPNGGGAGDSLPGSPSRGLGPPSPPAPPRGPAGEAGASPPVRRVRVVK
  QEAGGLGISIKGGRENRMPILISKIFPGLAADQSRALRLGDAILSVNGTDLRQATHDQAV
  QALKRAGKEVLLEVKFIREVTPYIKKPSLVSDLPWEGAAPQSPSFSGSEDSGSPKHQNST
  KDRKIIPLKMCFAARNLSMPDLENRLIELHSPDSRNTLILRCKDTATAHSWFVAIHTNIM
  ALLPQVLAELNAMLGATSTAGGSKEVKHIAWLAEQAKLDGGRQQWRPVLMAVTEKDLLLY
  DCMPWTRDAWASPCHSYPLVATRLVHSGSGCRSPSLGSDLTFATRTGSRQGIEMHLFRVE
  THRDLSSWTRILVQGCHAAAELIKEVSLGCMLNGQEVRLTIHYENGFTISRENGGSSSIL
  YRYPFERLKMSADDGIRNLYLDFGGPEGELTMDLHSCPKPIVFVLHTFLSAKVTRMGLLV
• Function: Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex. May play a role in the regulation of secretory granules via its interaction with PTPRN.
• Tissue Specificity: Ubiquitous. Isoform 1 is the predominant isoform. Weak level of isoform 2 is present in all tested tissues, except in liver and heart where it is highly expressed.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
  Viral myocarditis (hsa05416)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metabolic disorder	DIS71G5H	Strong	Biomarker	[1]

12 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 Beta-2-syntrophin (SNTB2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-2-syntrophin (SNTB2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-2-syntrophin (SNTB2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Beta-2-syntrophin (SNTB2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Beta-2-syntrophin (SNTB2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Beta-2-syntrophin (SNTB2).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Beta-2-syntrophin (SNTB2).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Beta-2-syntrophin (SNTB2).	[2]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Beta-2-syntrophin (SNTB2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Beta-2-syntrophin (SNTB2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Beta-2-syntrophin (SNTB2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Beta-2-syntrophin (SNTB2).	[14]

3 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 affects the phosphorylation of Beta-2-syntrophin (SNTB2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Beta-2-syntrophin (SNTB2).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Beta-2-syntrophin (SNTB2).	[12]

References

• [1] Adipocyte Hypertrophy and Improved Postprandial Lipid Response in Beta 2 Syntrophin Deficient Mice.Cell Physiol Biochem. 2019;52(5):1151-1165. doi: 10.33594/000000078.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] 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.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [11] 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.
• [12] 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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.