Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEL5B2H)

• DOT Name: Synapse-associated protein 1 (SYAP1)
• Synonyms: BSD domain-containing signal transducer and Akt interactor protein; BSTA
• Gene Name: SYAP1
• UniProt ID: SYAP1_HUMAN
• PDB ID: 1X3A
• Pfam ID: PF03909
• Sequence:
  MFRGLSSWLGLQQPVAGGGQPNGDAPPEQPSETVAESAEEELQQAGDQELLHQAKDFGNY
  LFNFASAATKKITESVAETAQTIKKSVEEGKIDGIIDKTIIGDFQKEQKKFVEEQHTKKS
  EAAVPPWVDTNDEETIQQQILALSADKRNFLRDPPAGVQFNFDFDQMYPVALVMLQEDEL
  LSKMRFALVPKLVKEEVFWRNYFYRVSLIKQSAQLTALAAQQQAAGKEEKSNGREQDLPL
  AEAVRPKTPPVVIKSQLKTQEDEEEISTSPGVSEFVSDAFDACNLNQEDLRKEMEQLVLD
  KKQEETAVLEEDSADWEKELQQELQEYEVVTESEKRDENWDKEIEKMLQEEN
• Function: Plays a role in adipocyte differentiation by promoting mTORC2-mediated phosphorylation of AKT1 at 'Ser-473' after growth factor stimulation.
• Tissue Specificity: Expressed in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas .

Molecular Interaction Atlas (MIA) of This DOT

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 Synapse-associated protein 1 (SYAP1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Synapse-associated protein 1 (SYAP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Synapse-associated protein 1 (SYAP1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synapse-associated protein 1 (SYAP1).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Synapse-associated protein 1 (SYAP1).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Synapse-associated protein 1 (SYAP1).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Synapse-associated protein 1 (SYAP1).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Synapse-associated protein 1 (SYAP1).	[9]

2 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 Synapse-associated protein 1 (SYAP1).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Synapse-associated protein 1 (SYAP1).	[8]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.