Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8TUN64)

• DOT Name: Syntaxin-17 (STX17)
• Gene Name: STX17
• Related Disease:
  Advanced cancer
  Alopecia areata
  Hepatocellular carcinoma
  Retinoblastoma
  Cardiomyopathy
• UniProt ID: STX17_HUMAN
• PDB ID: 4WY4; 7BV4; 7BV6
• Sequence:
  MSEDEEKVKLRRLEPAIQKFIKIVIPTDLERLRKHQINIEKYQRCRIWDKLHEEHINAGR
  TVQQLRSNIREIEKLCLKVRKDDLVLLKRMIDPVKEEASAATAEFLQLHLESVEELKKQF
  NDEETLLQPPLTRSMTVGGAFHTTEAEASSQSLTQIYALPEIPQDQNAAESWETLEADLI
  ELSQLVTDFSLLVNSQQEKIDSIADHVNSAAVNVEEGTKNLGKAAKYKLAALPVAGALIG
  GMVGGPIGLLAGFKVAGIAAALGGGVLGFTGGKLIQRKKQKMMEKLTSSCPDLPSQTDKK
  CS
• Function: SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. STX17 is a SNARE of the autophagosome involved in autophagy through the direct control of autophagosome membrane fusion with the lysosome membrane. May also play a role in the early secretory pathway where it may maintain the architecture of the endoplasmic reticulum-Golgi intermediate compartment/ERGIC and Golgi and/or regulate transport between the endoplasmic reticulum, the ERGIC and the Golgi.
• KEGG Pathway:
  S.RE interactions in vesicular transport (hsa04130)
  Autophagy - animal (hsa04140)
• Reactome Pathway: COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alopecia areata	DIS0XXBJ	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[3]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[4]

7 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-17 (STX17).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Syntaxin-17 (STX17).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Syntaxin-17 (STX17).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Syntaxin-17 (STX17).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Syntaxin-17 (STX17).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Syntaxin-17 (STX17).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Syntaxin-17 (STX17).	[12]

1 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-17 (STX17).	[11]

References

• [1] The subcellular localization of syntaxin 17 varies among different cell types and is altered in some malignant cells.J Histochem Cytochem. 2005 Nov;53(11):1371-82. doi: 10.1369/jhc.4A6508.2005. Epub 2005 Jun 13.
• [2] Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.Nature. 2010 Jul 1;466(7302):113-7. doi: 10.1038/nature09114.
• [3] MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation.J Cell Biochem. 2018 May;119(5):3853-3863. doi: 10.1002/jcb.26464. Epub 2018 Jan 19.
• [4] LAMP-2B regulates human cardiomyocyte function by mediating autophagosome-lysosome fusion.Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):556-565. doi: 10.1073/pnas.1808618116. Epub 2018 Dec 24.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] 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.
• [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] 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.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.