Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWG7F3H)

• DOT Name: 14-3-3 protein theta
• Synonyms: 14-3-3 protein T-cell; 14-3-3 protein tau; Protein HS1
• Gene Name: YWHAQ
• UniProt ID: 1433T_HUMAN
• PDB ID: 2BTP; 5IQP; 6BCR; 6BD2; 6BQT; 6KZG; 6KZH
• Pfam ID: PF00244
• Sequence:
  MEKTELIQKAKLAEQAERYDDMATCMKAVTEQGAELSNEERNLLSVAYKNVVGGRRSAWR
  VISSIEQKTDTSDKKLQLIKDYREKVESELRSICTTVLELLDKYLIANATNPESKVFYLK
  MKGDYFRYLAEVACGDDRKQTIDNSQGAYQEAFDISKKEMQPTHPIRLGLALNFSVFYYE
  ILNNPELACTLAKTAFDEAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDSAGEECDAA
  EGAEN
• 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: Abundantly expressed in brain, heart and pancreas, and at lower levels in kidney and placenta. Up-regulated in the lumbar spinal cord from patients with sporadic amyotrophic lateral sclerosis (ALS) compared with controls, with highest levels of expression in individuals with predominant lower motor neuron involvement.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  PI3K-Akt sig.ling pathway (hsa04151)
  Hippo sig.ling pathway (hsa04390)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  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)
  Regulation of localization of FOXO transcription factors (R-HSA-9614399)
  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
Vinblastine	DM5TVS3	Approved	14-3-3 protein theta affects the response to substance of Vinblastine.	[21]
PEITC	DMOMN31	Phase 2	14-3-3 protein theta affects the binding of PEITC.	[22]
Sulforaphane	DMQY3L0	Investigative	14-3-3 protein theta affects the binding of Sulforaphane.	[22]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of 14-3-3 protein theta.	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the ubiquitination of 14-3-3 protein theta.	[5]
I3C	DMIGFOR	Phase 3	I3C decreases the phosphorylation of 14-3-3 protein theta.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of 14-3-3 protein theta.	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 14-3-3 protein theta.	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 14-3-3 protein theta.	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of 14-3-3 protein theta.	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of 14-3-3 protein theta.	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of 14-3-3 protein theta.	[8]
Aspirin	DM672AH	Approved	Aspirin increases the expression of 14-3-3 protein theta.	[9]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of 14-3-3 protein theta.	[10]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of 14-3-3 protein theta.	[8]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of 14-3-3 protein theta.	[11]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of 14-3-3 protein theta.	[11]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of 14-3-3 protein theta.	[12]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of 14-3-3 protein theta.	[13]
Thiotepa	DMIZKOP	Approved	Thiotepa increases the expression of 14-3-3 protein theta.	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of 14-3-3 protein theta.	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of 14-3-3 protein theta.	[17]
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of 14-3-3 protein theta.	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 14-3-3 protein theta.	[19]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of 14-3-3 protein theta.	[20]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of 14-3-3 protein theta.	[18]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the localization of 14-3-3 protein theta.	[15]

References

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• [11] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
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