Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6CV0CA)

• DOT Name: Synaptophysin-like protein 2 (SYPL2)
• Gene Name: SYPL2
• Related Disease:
  Alzheimer disease
  Aortic valve stenosis
  Cardiac failure
  Congestive heart failure
• UniProt ID: SYPL2_HUMAN
• Pfam ID: PF01284
• Sequence:
  MSSTESAGRTADKSPRQQVDRLLVGLRWRRLEEPLGFIKVLQWLFAIFAFGSCGSYSGET
  GAMVRCNNEAKDVSSIIVAFGYPFRLHRIQYEMPLCDEESSSKTMHLMGDFSAPAEFFVT
  LGIFSFFYTMAALVIYLRFHNLYTENKRFPLVDFCVTVSFTFFWLVAAAAWGKGLTDVKG
  ATRPSSLTAAMSVCHGEEAVCSAGATPSMGLANISVLFGFINFFLWAGNCWFVFKETPWH
  GQGQGQDQDQDQDQGQGPSQESAAEQGAVEKQ
• Function: Involved in communication between the T-tubular and junctional sarcoplasmic reticulum (SR) membranes.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Aortic valve stenosis	DISW7AQ9	Strong	Genetic Variation	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Synaptophysin-like protein 2 (SYPL2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptophysin-like protein 2 (SYPL2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Synaptophysin-like protein 2 (SYPL2).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Synaptophysin-like protein 2 (SYPL2).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Synaptophysin-like protein 2 (SYPL2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synaptophysin-like protein 2 (SYPL2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Synaptophysin-like protein 2 (SYPL2).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Synaptophysin-like protein 2 (SYPL2).	[12]

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 Synaptophysin-like protein 2 (SYPL2).	[9]

References

• [1] Mitsugumin 29 is transcriptionally induced in senile plaque-associated astrocytes.Brain Res. 2012 Mar 2;1441:9-16. doi: 10.1016/j.brainres.2011.12.062. Epub 2012 Jan 12.
• [2] Impact of Vascular Hemodynamics on Aortic Stenosis Evaluation: New Insights Into the Pathophysiology of Normal Flow-Small Aortic Valve Area-Low Gradient Pattern.J Am Heart Assoc. 2017 Jul 7;6(7):e006276. doi: 10.1161/JAHA.117.006276.
• [3] Mitsugumin 29 regulates t-tubule architecture in the failing heart.Sci Rep. 2017 Jul 13;7(1):5328. doi: 10.1038/s41598-017-05284-2.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [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] 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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.