Details of Drug Off-Target (DOT)

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

DOT Name Syntaxin-binding protein 5-like (STXBP5L)
Synonyms Lethal(2) giant larvae protein homolog 4; Tomosyn-2
Gene Name STXBP5L
Related Disease
Schizophrenia ( )
Non-insulin dependent diabetes ( )
UniProt ID
STB5L_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
MKKFNFRKVLDGLTASSPGSGSSSGSNSGGGAGSGSVHPAGTAGVLREEIQETLTSEYFQ
ICKTVRHGFPHQPTALAFDPVQKILAIGTRTGAIRILGRPGVDCYCQHESGAAVLQLQFL
INEGALVSASSDDTLHLWNLRQKRPAILHSLKFNRERITYCHLPFQSKWLYVGTERGNTH
IVNIESFILSGYVIMWNKAIELSTKTHPGPVVHLSDSPRDEGKLLIGYENGTVVFWDLKS
KRAELRVYYDEAIHSIDWHHEGKQFMCSHSDGSLTLWNLKSPSRPFQTTIPHGKSQREGR
KSESCKPILKVEYKTCKNSEPFIIFSGGLSYDKACRRPSLTIMHGKAITVLEMDHPIVEF
LTLCETPYPNEFQEPYAVVVLLEKDLIVVDLTQSNFPIFENPYPMDIHESPVTCTAYFAD
CPPDLILVLYSIGVKHKKQGYSNKEWPISGGAWNLGAQTYPEIIITGHADGSIKFWDASA
ITLQMLYKLKTSKVFEKQKVGEGKQTCEIVEEDPFAIQMIYWCPESRIFCVSGVSAYVII
YKFSRHEITTEIVSLEVRLQYDVEDIITPEPETSPPFPDLSAQLPSSRSLSGSTNTVASE
GVTKDSIPCLNVKTRPVRMPPGYQAELVIQLVWVDGEPPQQITSLAVSSAYGIVAFGNCN
GLAVVDFIQKTVLLSMGTIDLYRSSDLYQRQPRSPRKNKQFIADNFCMRGLSNFYPDLTK
RIRTSYQSLTELNDSPVPLELERCKSPTSDHVNGHCTSPTSQSCSSGKRLSSADVSKVNR
WGPGRPPFRKAQSAACMEISLPVTTEENRENSYNRSRSSSISSIDKDSKEAITALYFMDS
FARKNDSTISPCLFVGTSLGMVLIISLNLPLADEQRFTEPVMVLPSGTFLSLKGAVLTFS
CMDRMGGLMQPPYEVWRDPNNIDENEKSWRRKVVMNSSSASQEIGDHQYTIICSEKQAKV
FSLPSQTCLYVHNITETSFILQANVVVMCSSACLACFCANGHIMIMSLPSLRPMLDVNYL
PLTDMRIARTFCFTNEGQALYLVSPTEIQRLTYSQEMCDNLQDMLGDLFTPIETPEAQNR
GFLKGLFGGSGQTFDREELFGEASAGKASRSLAQHIPGPGSIEGMKGAAGGVMGELTRAR
IALDERGQRLGELEEKTAGMMTSAEAFSKHAHELMLKYKDKKWYQF
Function
Plays a role in vesicle trafficking and exocytosis inhibition. In pancreatic beta-cells, inhibits insulin secretion probably by interacting with and regulating STX1A and STX4, key t-SNARE proteins involved in the fusion of insulin granules to the plasma membrane. Also plays a role in neurotransmitter release by inhibiting basal acetylcholine release from axon terminals and by preventing synaptic fatigue upon repetitive stimulation. Promotes as well axonal outgrowth.
Tissue Specificity Detected in kidney, hippocampus and lung carcinoma.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Schizophrenia DISSRV2N Strong Genetic Variation [1]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Syntaxin-binding protein 5-like (STXBP5L). [3]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Syntaxin-binding protein 5-like (STXBP5L). [4]
Testosterone Undecanoate DMZO10Y Approved Testosterone Undecanoate increases the expression of Syntaxin-binding protein 5-like (STXBP5L). [5]
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2 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 Syntaxin-binding protein 5-like (STXBP5L). [6]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Syntaxin-binding protein 5-like (STXBP5L). [7]
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References

1 Identifying the genetic risk factors for treatment response to lurasidone by genome-wide association study: A meta-analysis of samples from three independent clinical trials.Schizophr Res. 2018 Sep;199:203-213. doi: 10.1016/j.schres.2018.04.006. Epub 2018 May 2.
2 Positional cloning of a type 2 diabetes quantitative trait locus; tomosyn-2, a negative regulator of insulin secretion.PLoS Genet. 2011 Oct;7(10):e1002323. doi: 10.1371/journal.pgen.1002323. Epub 2011 Oct 6.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
5 Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
6 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.
7 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.