Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAO5WIU)

• DOT Name: Synaptic vesicle glycoprotein 2B (SV2B)
• Gene Name: SV2B
• Related Disease:
  Acute leukaemia
  Alzheimer disease
  Epilepsy
  Huntington disease
  Neoplasm
  Nephropathy
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Acute myelogenous leukaemia
• UniProt ID: SV2B_HUMAN
• Pfam ID: PF07690 ; PF13599 ; PF00083
• Sequence:
  MDDYKYQDNYGGYAPSDGYYRGNESNPEEDAQSDVTEGHDEEDEIYEGEYQGIPHPDDVK
  AKQAKMAPSRMDSLRGQTDLMAERLEDEEQLAHQYETIMDECGHGRFQWILFFVLGLALM
  ADGVEVFVVSFALPSAEKDMCLSSSKKGMLGMIVYLGMMAGAFILGGLADKLGRKRVLSM
  SLAVNASFASLSSFVQGYGAFLFCRLISGIGIGGALPIVFAYFSEFLSREKRGEHLSWLG
  IFWMTGGLYASAMAWSIIPHYGWGFSMGTNYHFHSWRVFVIVCALPCTVSMVALKFMPES
  PRFLLEMGKHDEAWMILKQVHDTNMRAKGTPEKVFTVSNIKTPKQMDEFIEIQSSTGTWY
  QRWLVRFKTIFKQVWDNALYCVMGPYRMNTLILAVVWFAMAFSYYGLTVWFPDMIRYFQD
  EEYKSKMKVFFGEHVYGATINFTMENQIHQHGKLVNDKFTRMYFKHVLFEDTFFDECYFE
  DVTSTDTYFKNCTIESTIFYNTDLYEHKFINCRFINSTFLEQKEGCHMDLEQDNDFLIYL
  VSFLGSLSVLPGNIISALLMDRIGRLKMIGGSMLISAVCCFFLFFGNSESAMIGWQCLFC
  GTSIAAWNALDVITVELYPTNQRATAFGILNGLCKFGAILGNTIFASFVGITKVVPILLA
  AASLVGGGLIALRLPETREQVLM
• Function: Probably plays a role in the control of regulated secretion in neural and endocrine cells; (Microbial infection) Receptor for the C.botulinum neurotoxin type A2 (BoNT/A, botA); glycosylation is not essential but enhances the interaction. Probably also serves as a receptor for the closely related C.botulinum neurotoxin type A1.
• KEGG Pathway: ECM-receptor interaction (hsa04512)
• Reactome Pathway:
  Toxicity of botulinum toxin type A (botA) (R-HSA-5250968)
  Toxicity of botulinum toxin type F (botF) (R-HSA-5250981)
  Toxicity of botulinum toxin type E (botE) (R-HSA-5250992)
  Toxicity of botulinum toxin type D (botD) (R-HSA-5250955)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Epilepsy	DISBB28L	Strong	Genetic Variation	[3]
Huntington disease	DISQPLA4	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Nephropathy	DISXWP4P	Strong	Altered Expression	[6]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[5]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Saquinavir	DMG814N	Approved	Synaptic vesicle glycoprotein 2B (SV2B) affects the response to substance of Saquinavir.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Synaptic vesicle glycoprotein 2B (SV2B).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptic vesicle glycoprotein 2B (SV2B).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Synaptic vesicle glycoprotein 2B (SV2B).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Synaptic vesicle glycoprotein 2B (SV2B).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Synaptic vesicle glycoprotein 2B (SV2B).	[11]

References

• [1] Identification of a novel fusion gene involving RUNX1 and the antisense strand of SV2B in a BCR-ABL1-positive acute leukemia.Genes Chromosomes Cancer. 2013 Dec;52(12):1114-22. doi: 10.1002/gcc.22105. Epub 2013 Oct 3.
• [2] The Synaptic Vesicle Glycoprotein 2: Structure, Function, and Disease Relevance.ACS Chem Neurosci. 2019 Sep 18;10(9):3927-3938. doi: 10.1021/acschemneuro.9b00351. Epub 2019 Aug 23.
• [3] No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy.Epilepsy Res. 2009 Jan;83(1):44-51. doi: 10.1016/j.eplepsyres.2008.09.003. Epub 2008 Oct 31.
• [4] Mutant Huntingtin Causes a Selective Decrease in the Expression of Synaptic Vesicle Protein 2C.Neurosci Bull. 2018 Oct;34(5):747-758. doi: 10.1007/s12264-018-0230-x. Epub 2018 Apr 30.
• [5] Molecular characterization of prostatic small-cell neuroendocrine carcinoma.Prostate. 2003 Apr 1;55(1):55-64. doi: 10.1002/pros.10217.
• [6] Synaptic vesicle protein 2B is expressed in podocyte, and its expression is altered in proteinuric glomeruli.J Am Soc Nephrol. 2006 Oct;17(10):2748-59. doi: 10.1681/ASN.2005121293. Epub 2006 Aug 30.
• [7] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [8] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] 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.
• [12] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [13] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.