Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ0024B)

• DOT Name: Syntaxin-5 (STX5)
• Gene Name: STX5
• Related Disease:
  Advanced cancer
  Endometriosis
  Spondyloepiphyseal dysplasia tarda, X-linked
  Unverricht-Lundborg syndrome
  Congenital disorder of glycosylation, type IIaa
  Non-insulin dependent diabetes
  Rett syndrome
• UniProt ID: STX5_HUMAN
• PDB ID: 3EFO
• Pfam ID: PF05739 ; PF11416
• Sequence:
  MIPRKRYGSKNTDQGVYLGLSKTQVLSPATAGSSSSDIAPLPPPVTLVPPPPDTMSCRDR
  TQEFLSACKSLQTRQNGIQTNKPALRAVRQRSEFTLMAKRIGKDLSNTFAKLEKLTILAK
  RKSLFDDKAVEIEELTYIIKQDINSLNKQIAQLQDFVRAKGSQSGRHLQTHSNTIVVSLQ
  SKLASMSNDFKSVLEVRTENLKQQRSRREQFSRAPVSALPLAPNHLGGGAVVLGAESHAS
  KDVAIDMMDSRTSQQLQLIDEQDSYIQSRADTMQNIESTIVELGSIFQQLAHMVKEQEET
  IQRIDENVLGAQLDVEAAHSEILKYFQSVTSNRWLMVKIFLILIVFFIIFVVFLA
• Function: Mediates endoplasmic reticulum to Golgi transport. Together with p115/USO1 and GM130/GOLGA2, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus; [Isoform 2]: Required for Golgi to endoplasmic reticulum retrogade transport, and for intra-Golgi transport; (Microbial infection) Required for the efficient production of infectious virion during human cytomegalovirus infection. Mechanistically, participates in the formation of the cytoplasmic viral assembly compartment where tegument acquisition and envelopment occur.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway:
  Cargo concentration in the ER (R-HSA-5694530)
  COPI-mediated anterograde transport (R-HSA-6807878)
  Intra-Golgi traffic (R-HSA-6811438)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOC GTPase cycle (R-HSA-9013106)
  RHOG GTPase cycle (R-HSA-9013408)
  Insertion of tail-anchored proteins into the endoplasmic reticulum membrane (R-HSA-9609523)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Endometriosis	DISX1AG8	Strong	Biomarker	[1]
Spondyloepiphyseal dysplasia tarda, X-linked	DIS9EL3M	Strong	Genetic Variation	[2]
Unverricht-Lundborg syndrome	DISG4WLX	Strong	Biomarker	[3]
Congenital disorder of glycosylation, type IIaa	DISP5HU0	Limited	Autosomal recessive	[4]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[5]
Rett syndrome	DISGG5UV	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Syntaxin-5 (STX5).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Syntaxin-5 (STX5).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Syntaxin-5 (STX5).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Syntaxin-5 (STX5).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Syntaxin-5 (STX5).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Syntaxin-5 (STX5).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Syntaxin-5 (STX5).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Syntaxin-5 (STX5).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntaxin-5 (STX5).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Syntaxin-5 (STX5).	[17]

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 decreases the methylation of Syntaxin-5 (STX5).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Syntaxin-5 (STX5).	[18]

References

• [1] Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal-Mild Endometriosis.Reprod Sci. 2017 Mar;24(3):413-420. doi: 10.1177/1933719116657190. Epub 2016 Sep 27.
• [2] A trs20 mutation that mimics an SEDT-causing mutation blocks selective and non-selective autophagy: a model for TRAPP III organization.Traffic. 2013 Oct;14(10):1091-104. doi: 10.1111/tra.12095. Epub 2013 Aug 15.
• [3] Functional assays for the assessment of the pathogenicity of variants of GOSR2, an ER-to-Golgi SNARE involved in progressive myoclonus epilepsies.Dis Model Mech. 2017 Dec 19;10(12):1391-1398. doi: 10.1242/dmm.029132.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [5] The assembly of lipid droplets and its relation to cellular insulin sensitivity.Biochem Soc Trans. 2009 Oct;37(Pt 5):981-5. doi: 10.1042/BST0370981.
• [6] Analysis of gene expression in Ca(2+)-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways.Neurosci Lett. 2017 Feb 3;639:88-93. doi: 10.1016/j.neulet.2016.12.068. Epub 2016 Dec 29.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] 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.
• [13] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] 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.