Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP0R3S5)

• DOT Name: Synaptotagmin-like protein 1 (SYTL1)
• Synonyms: Exophilin-7; Protein JFC1
• Gene Name: SYTL1
• Related Disease:
  Neoplasm
  Kennedy disease
  Schistosomiasis
• UniProt ID: SYTL1_HUMAN
• Pfam ID: PF00168
• Sequence:
  MPQRGHPSQEGLWALPSLPMAHGPKPETEGLLDLSFLTEEEQEAIAGVLQRDARLRQLEE
  GRVSKLRASVADPGQLKILTGDWFQEARSQRHHNAHFGSDLVRASMRRKKSTRGDQAPGH
  DREAEAAVKEKEEGPEPRLTIDEAPQERLRETEGPDFPSPSVPLKASDPEEASQAQEDPG
  QGDQQVCAEEADPELEPASGGEQEPRPQQAQTKAASQILENGEEAPGPDPSLDRMLSSSS
  SVSSLNSSTLSGSQMSLSGDAEAVQVRGSVHFALHYEPGAAELRVHVIQCQGLAAARRRR
  SDPYVKSYLLPDKQSKRKTAVKKRNLNPVFNETLRYSVPQAELQGRVLSLSVWHRESLGR
  NIFLGEVEVPLDTWDWGSEPTWLPLQPRVPPSPDDLPSRGLLALSLKYVPAGSEGAGLPP
  SGELHFWVKEARDLLPLRAGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYD
  GFGPADLRQACAELSLWDHGALANRQLGGTRLSLGTGSSYGLQVPWMDSTPEEKQLWQAL
  LEQPCEWVDGLLPLRTNLAPRT
• Function: May play a role in vesicle trafficking. Binds phosphatidylinositol 3,4,5-trisphosphate. Acts as a RAB27A effector protein and may play a role in cytotoxic granule exocytosis in lymphocytes.
• Tissue Specificity: Highly expressed in bone marrow and lymphoid tissues. Detected at lower levels in cerebellum, occipital lobe, prostate, stomach, kidney, appendix, lung and trachea. Expressed in cytotoxic T-lymphocytes (CTL).
• Reactome Pathway: TBC/RABGAPs (R-HSA-8854214)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Kennedy disease	DISXZVM1	Limited	Altered Expression	[2]
Schistosomiasis	DIS6PD44	Limited	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 1 (SYTL1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Synaptotagmin-like protein 1 (SYTL1).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Synaptotagmin-like protein 1 (SYTL1).	[17]

12 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 Synaptotagmin-like protein 1 (SYTL1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Synaptotagmin-like protein 1 (SYTL1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptotagmin-like protein 1 (SYTL1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Synaptotagmin-like protein 1 (SYTL1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Synaptotagmin-like protein 1 (SYTL1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Synaptotagmin-like protein 1 (SYTL1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Synaptotagmin-like protein 1 (SYTL1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Synaptotagmin-like protein 1 (SYTL1).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Synaptotagmin-like protein 1 (SYTL1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Synaptotagmin-like protein 1 (SYTL1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Synaptotagmin-like protein 1 (SYTL1).	[16]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Synaptotagmin-like protein 1 (SYTL1).	[18]

References

• [1] Deregulation of Rab and Rab effector genes in bladder cancer.PLoS One. 2012;7(6):e39469. doi: 10.1371/journal.pone.0039469. Epub 2012 Jun 19.
• [2] CD24 cell surface expression in Mvt1 mammary cancer cells serves as a biomarker for sensitivity to anti-IGF1R therapy.Breast Cancer Res. 2016 May 14;18(1):51. doi: 10.1186/s13058-016-0711-7.
• [3] Saposin-like proteins are expressed in the gastrodermis of Schistosoma mansoni and are immunogenic in natural infections.Int J Infect Dis. 2008 Nov;12(6):e39-47. doi: 10.1016/j.ijid.2007.10.007. Epub 2008 Jun 20.
• [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] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [9] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] 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.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.
• [15] 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.
• [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] 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.
• [18] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.