Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE3M7QB)

DOT Name Syntaxin-binding protein 5 (STXBP5)
Synonyms Lethal(2) giant larvae protein homolog 3; Tomosyn-1
Gene Name STXBP5
Related Disease
Neoplasm ( )
Non-small-cell lung cancer ( )
Von willebrand disease ( )
Von Willebrand disease 1 ( )
Von Willebrand disease 2 ( )
UniProt ID
STXB5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF08596 ; PF08366 ; PF00400
Sequence
MRKFNIRKVLDGLTAGSSSASQQQQQQHPPGNREPEIQETLQSEHFQLCKTVRHGFPYQP
SALAFDPVQKILAVGTQTGALRLFGRPGVECYCQHDSGAAVIQLQFLINEGALVSALADD
TLHLWNLRQKRPAILHSLKFCRERVTFCHLPFQSKWLYVGTERGNIHIVNVESFTLSGYV
IMWNKAIELSSKSHPGPVVHISDNPMDEGKLLIGFESGTVVLWDLKSKKADYRYTYDEAI
HSVAWHHEGKQFICSHSDGTLTIWNVRSPAKPVQTITPHGKQLKDGKKPEPCKPILKVEF
KTTRSGEPFIILSGGLSYDTVGRRPCLTVMHGKSTAVLEMDYSIVDFLTLCETPYPNDFQ
EPYAVVVLLEKDLVLIDLAQNGYPIFENPYPLSIHESPVTCCEYFADCPVDLIPALYSVG
ARQKRQGYSKKEWPINGGNWGLGAQSYPEIIITGHADGSVKFWDASAITLQVLYKLKTSK
VFEKSRNKDDRPNTDIVDEDPYAIQIISWCPESRMLCIAGVSAHVIIYRFSKQEVITEVI
PMLEVRLLYEINDVETPEGEQPPPLPTPVGGSNPQPIPPQSHPSTSSSSSDGLRDNVPCL
KVKNSPLKQSPGYQTELVIQLVWVGGEPPQQITSLAVNSSYGLVVFGNCNGIAMVDYLQK
AVLLNLGTIELYGSNDPYRREPRSPRKSRQPSGAGLCDISEGTVVPEDRCKSPTSGSSSP
HNSDDEQKMNNFIEKVKTKSRKFSKMVANDIAKMSRKLSLPTDLKPDLDVKDNSFSRSRS
SSVTSIDKESREAISALHFCETFTRKTDSSPSPCLWVGTTLGTVLVIALNLPPGGEQRLL
QPVIVSPSGTILRLKGAILRMAFLDTTGCLIPPAYEPWREHNVPEEKDEKEKLKKRRPVS
VSPSSSQEISENQYAVICSEKQAKVISLPTQNCAYKQNITETSFVLRGDIVALSNSICLA
CFCANGHIMTFSLPSLRPLLDVYYLPLTNMRIARTFCFTNNGQALYLVSPTEIQRLTYSQ
ETCENLQEMLGELFTPVETPEAPNRGFFKGLFGGGAQSLDREELFGESSSGKASRSLAQH
IPGPGGIEGVKGAASGVVGELARARLALDERGQKLGDLEERTAAMLSSAESFSKHAHEIM
LKYKDKKWYQF
Function
Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Strong Genetic Variation [1]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [2]
Von willebrand disease DIS3TZCH Strong Altered Expression [3]
Von Willebrand disease 1 DISUGLZA Strong Genetic Variation [4]
Von Willebrand disease 2 DISEYUBR Strong Genetic Variation [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 Syntaxin-binding protein 5 (STXBP5). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Syntaxin-binding protein 5 (STXBP5). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Syntaxin-binding protein 5 (STXBP5). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Syntaxin-binding protein 5 (STXBP5). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Syntaxin-binding protein 5 (STXBP5). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Syntaxin-binding protein 5 (STXBP5). [10]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Syntaxin-binding protein 5 (STXBP5). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Syntaxin-binding protein 5 (STXBP5). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Syntaxin-binding protein 5 (STXBP5). [15]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Syntaxin-binding protein 5 (STXBP5). [16]
AHPN DM8G6O4 Investigative AHPN increases the expression of Syntaxin-binding protein 5 (STXBP5). [17]
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⏷ Show the Full List of 11 Drug(s)
2 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 Syntaxin-binding protein 5 (STXBP5). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Syntaxin-binding protein 5 (STXBP5). [13]
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References

1 Molecular analysis of germline t(3;6) and t(3;12) associated with conventional renal cell carcinomas indicates their rate-limiting role and supports the three-hit model of carcinogenesis.Cancer Genet Cytogenet. 2010 Aug;201(1):15-23. doi: 10.1016/j.cancergencyto.2010.04.018.
2 Long noncoding RNA STXBP5-AS1 inhibits cell proliferation, migration, and invasion via preventing the PI3K/AKT against STXBP5 expression in non-small-cell lung carcinoma.J Cell Biochem. 2019 May;120(5):7489-7498. doi: 10.1002/jcb.28023. Epub 2018 Nov 18.
3 CLEC4M and STXBP5 gene variations contribute to von Willebrand factor level variation in von Willebrand disease.J Thromb Haemost. 2015 Jun;13(6):956-66. doi: 10.1111/jth.12927. Epub 2015 May 9.
4 Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand Disease patients.PLoS One. 2018 Feb 1;13(2):e0192024. doi: 10.1371/journal.pone.0192024. eCollection 2018.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
7 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.
8 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.
9 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.
10 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
11 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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 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.
15 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
16 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
17 Identification of retinoid-modulated proteins in squamous carcinoma cells using high-throughput immunoblotting. Cancer Res. 2004 Apr 1;64(7):2439-48. doi: 10.1158/0008-5472.can-03-2643.