Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP8NJFJ)

• DOT Name: 14-3-3 protein eta
• Synonyms: Protein AS1
• Gene Name: YWHAH
• UniProt ID: 1433F_HUMAN
• PDB ID: 2C63; 2C74; 7NMZ
• Pfam ID: PF00244
• Sequence:
  MGDREQLLQRARLAEQAERYDDMASAMKAVTELNEPLSNEDRNLLSVAYKNVVGARRSSW
  RVISSIEQKTMADGNEKKLEKVKAYREKIEKELETVCNDVLSLLDKFLIKNCNDFQYESK
  VFYLKMKGDYYRYLAEVASGEKKNSVVEASEAAYKEAFEISKEQMQPTHPIRLGLALNFS
  VFYYEIQNAPEQACLLAKQAFDDAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDQQDE
  EAGEGN
• Function: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1.
• Tissue Specificity: Expressed mainly in the brain and present in other tissues albeit at lower levels.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  PI3K-Akt sig.ling pathway (hsa04151)
  Hippo sig.ling pathway (hsa04390)
  Hepatitis C (hsa05160)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)
  RHO GTPases activate PKNs (R-HSA-5625740)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Chk1/Chk2(Cds1) mediated inactivation of Cyclin B (R-HSA-75035)
  SARS-CoV-1 targets host intracellular signalling and regulatory pathways (R-HSA-9735871)
  SARS-CoV-2 targets host intracellular signalling and regulatory pathways (R-HSA-9755779)
  Activation of BAD and translocation to mitochondria (R-HSA-111447)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	14-3-3 protein eta decreases the response to substance of Doxorubicin.	[14]
Fluorouracil	DMUM7HZ	Approved	14-3-3 protein eta decreases the response to substance of Fluorouracil.	[14]
PEITC	DMOMN31	Phase 2	14-3-3 protein eta affects the binding of PEITC.	[15]

13 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 14-3-3 protein eta.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 14-3-3 protein eta.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 14-3-3 protein eta.	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 14-3-3 protein eta.	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of 14-3-3 protein eta.	[5]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of 14-3-3 protein eta.	[6]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of 14-3-3 protein eta.	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 14-3-3 protein eta.	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of 14-3-3 protein eta.	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 14-3-3 protein eta.	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of 14-3-3 protein eta.	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 14-3-3 protein eta.	[12]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of 14-3-3 protein eta.	[13]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [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] Characterization of arsenic trioxide resistant clones derived from Jurkat leukemia T cell line: focus on PI3K/Akt signaling pathway. Chem Biol Interact. 2013 Oct 5;205(3):198-211. doi: 10.1016/j.cbi.2013.07.011. Epub 2013 Aug 2.
• [6] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [7] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [8] 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.
• [9] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [14] Arsenic trioxide reverses the chemoresistance in hepatocellular carcinoma: a targeted intervention of 14-3-3/NF-B feedback loop. J Exp Clin Cancer Res. 2018 Dec 20;37(1):321. doi: 10.1186/s13046-018-1005-y.
• [15] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.