Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6TPBA9)

• DOT Name: Synaptotagmin-like protein 3 (SYTL3)
• Synonyms: Exophilin-6
• Gene Name: SYTL3
• Related Disease:
  Cystic fibrosis
  Peripheral arterial disease
  Chediak-Higashi syndrome
• UniProt ID: SYTL3_HUMAN
• Pfam ID: PF00168 ; PF02318
• Sequence:
  MAQEIDLSALKELEREAILQVLYRDQAVQNTEEERTRKLKTHLQHLRWKGAKNTDWEHKE
  KCCARCQQVLGFLLHRGAVCRGCSHRVCAQCRVFLRGTHAWKCTVCFEDRNVKIKTGEWF
  YEERAKKFPTGGKHETVGGQLLQSYQKLSKISVVPPTPPPVSESQCSRSPGRLQEFGQFR
  GFNKSVENLFLSLATHVKKLSKSQNDMTSEKHLLATGPRQCVGQTERRSQSDTAVNVTTR
  KVSAPDILKPLNQEDPKCSTNPILKQQNLPSSPAPSTIFSGGFRHGSLISIDSTCTEMGN
  FDNANVTGEIEFAIHYCFKTHSLEICIKACKNLAYGEEKKKKCNPYVKTYLLPDRSSQGK
  RKTGVQRNTVDPTFQETLKYQVAPAQLVTRQLQVSVWHLGTLARRVFLGEVIIPLATWDF
  EDSTTQSFRWHPLRAKAEKYEDSVPQSNGELTVRAKLVLPSRPRKLQEAQEGTDQPSLHG
  QLCLVVLGAKNLPVRPDGTLNSFVKGCLTLPDQQKLRLKSPVLRKQACPQWKHSFVFSGV
  TPAQLRQSSLELTVWDQALFGMNDRLLGGTRLGSKGDTAVGGDACSLSKLQWQKVLSSPN
  LWTDMTLVLH
• Function: May act as Rab effector protein and play a role in vesicle trafficking. Binds phospholipids in the presence of calcium ions.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[1]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[2]
Chediak-Higashi syndrome	DISPJLLO	Disputed	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Synaptotagmin-like protein 3 (SYTL3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Synaptotagmin-like protein 3 (SYTL3).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Synaptotagmin-like protein 3 (SYTL3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptotagmin-like protein 3 (SYTL3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Synaptotagmin-like protein 3 (SYTL3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Synaptotagmin-like protein 3 (SYTL3).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Synaptotagmin-like protein 3 (SYTL3).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Synaptotagmin-like protein 3 (SYTL3).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Synaptotagmin-like protein 3 (SYTL3).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Synaptotagmin-like protein 3 (SYTL3).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synaptotagmin-like protein 3 (SYTL3).	[13]

References

• [1] Evaluation of respiratory dynamics by volumetric capnography during submaximal exercise protocol of six minutes on treadmill in cystic fibrosis patients.J Pediatr (Rio J). 2019 Jan-Feb;95(1):76-86. doi: 10.1016/j.jped.2017.10.007. Epub 2017 Nov 29.
• [2] Variants Associated with the Ankle Brachial Index Differ by Hispanic/Latino Ethnic Group: a genome-wide association study in the Hispanic Community Health Study/Study of Latinos.Sci Rep. 2019 Aug 6;9(1):11410. doi: 10.1038/s41598-019-47928-5.
• [3] LYST controls the biogenesis of the endosomal compartment required for secretory lysosome function.Traffic. 2015 Feb;16(2):191-203. doi: 10.1111/tra.12244. Epub 2015 Jan 6.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] 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.
• [14] 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.