Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE7OYQC)

• DOT Name: Synaptotagmin-like protein 5 (SYTL5)
• Gene Name: SYTL5
• Related Disease:
  Anorexia nervosa cachexia
  Bulimia nervosa
• UniProt ID: SYTL5_HUMAN
• Pfam ID: PF00168 ; PF02318
• Sequence:
  MSKNSEFINLSFLLDHEKEMILGVLKRDEYLKKVEDKRIRKLKNELLEAKRRSGKTQQEA
  SRVCVHCHRNLGLIFDRGDPCQACSLRVCRECRVAGPNGSWKCTVCDKIAQLRIITGEWF
  FEEKAKRFKQVNVLGTDVVRQSILRRSPGAEEVQSQEQTRQDAEKSDTSPVAGKKASHDG
  PKRKGFLLSKFRSATRGEIITPKTDTGRSYSLDLDGQHFRSLKSPPGSDRGSTGSSDLND
  QEPGPRTPKSSRSNGVTPGTQSSPAPSTRTVTSVISREYGFENSMDLAAIEGTSQELTKS
  HRRNTSGTPSIAVSGTSLSSDQSRSELDLSESFTEDSEDTVSIRSKSVPGALDKDSLEET
  EESIDALVSSQLSTNTHRLASGLSTTSLNSMMSVYSETGDYGNVKVSGEILLHISYCYKT
  GGLYIFVKNCRNLAIGDEKKQRTDAYVKSYLLPDKSRNNKRKTKIRTGTNPEFNETLKYT
  ISHTQLETRTLQLSVWHYDRFGRNSFLGEVEIPFDSWNFENPTDEWFVLQPKVEFAPDIG
  LQYKGELTVVLRYIPPEENLMLPPEQLQGNKTFKKGKKKESPVISGGILEVFIKEAKNLT
  AVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSGIHPQDIKNVCLEL
  TIWDKEAFSSNIFLGGVRLNSGSGVSHGKNVDWMDSQGEEQRLWQKMANNPGTPFEGVLM
  LRSSMGKCRL
• Function: May act as Rab effector protein and play a role in vesicle trafficking. Binds phospholipids.
• Tissue Specificity: Highly expressed in placenta and liver.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[1]
Bulimia nervosa	DISGQ59Y	Strong	Biomarker	[1]

11 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 Synaptotagmin-like protein 5 (SYTL5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptotagmin-like protein 5 (SYTL5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptotagmin-like protein 5 (SYTL5).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Synaptotagmin-like protein 5 (SYTL5).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptotagmin-like protein 5 (SYTL5).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Synaptotagmin-like protein 5 (SYTL5).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Synaptotagmin-like protein 5 (SYTL5).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Synaptotagmin-like protein 5 (SYTL5).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synaptotagmin-like protein 5 (SYTL5).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Synaptotagmin-like protein 5 (SYTL5).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Synaptotagmin-like protein 5 (SYTL5).	[5]

1 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 Synaptotagmin-like protein 5 (SYTL5).	[9]

References

• [1] Genetic variants associated with disordered eating.Int J Eat Disord. 2013 Sep;46(6):594-608. doi: 10.1002/eat.22133. Epub 2013 Apr 9.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [6] 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.
• [7] 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.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] 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.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.