Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGBS3RF)

• DOT Name: 14-3-3 protein beta/alpha
• Synonyms: Protein 1054; Protein kinase C inhibitor protein 1; KCIP-1
• Gene Name: YWHAB
• UniProt ID: 1433B_HUMAN
• PDB ID: 2BQ0; 2C23; 4DNK; 5N10; 6A5Q; 6BYK; 6GN0; 6GN8; 6GNJ; 6GNK; 6GNN; 6HEP; 8DP5; 8EQ8; 8EQH
• Pfam ID: PF00244
• Sequence:
  MTMDKSELVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSS
  WRVISSIEQKTERNEKKQQMGKEYREKIEAELQDICNDVLELLDKYLIPNATQPESKVFY
  LKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFY
  YEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGD
  AGEGEN
• 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. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13.
• 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)
  MTOR signalling (R-HSA-165159)
  mTORC1-mediated signalling (R-HSA-166208)
  Frs2-mediated activation (R-HSA-170968)
  ARMS-mediated activation (R-HSA-170984)
  Signaling by Hippo (R-HSA-2028269)
  Rap1 signalling (R-HSA-392517)
  Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA (R-HSA-450385)
  Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA (R-HSA-450513)
  RHO GTPases activate PKNs (R-HSA-5625740)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  RAF activation (R-HSA-5673000)
  MAP2K and MAPK activation (R-HSA-5674135)
  Negative regulation of MAPK pathway (R-HSA-5675221)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  Chk1/Chk2(Cds1) mediated inactivation of Cyclin B (R-HSA-75035)
  Regulation of localization of FOXO transcription factors (R-HSA-9614399)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  SHOC2 M1731 mutant abolishes MRAS complex function (R-HSA-9726840)
  Gain-of-function MRAS complexes activate RAF signaling (R-HSA-9726842)
  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 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	14-3-3 protein beta/alpha affects the binding of PEITC.	[21]
Sulforaphane	DMQY3L0	Investigative	14-3-3 protein beta/alpha affects the binding of Sulforaphane.	[21]

21 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 14-3-3 protein beta/alpha.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 14-3-3 protein beta/alpha.	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 14-3-3 protein beta/alpha.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 14-3-3 protein beta/alpha.	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 14-3-3 protein beta/alpha.	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of 14-3-3 protein beta/alpha.	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of 14-3-3 protein beta/alpha.	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of 14-3-3 protein beta/alpha.	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of 14-3-3 protein beta/alpha.	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of 14-3-3 protein beta/alpha.	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of 14-3-3 protein beta/alpha.	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of 14-3-3 protein beta/alpha.	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of 14-3-3 protein beta/alpha.	[9]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of 14-3-3 protein beta/alpha.	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of 14-3-3 protein beta/alpha.	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 14-3-3 protein beta/alpha.	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 14-3-3 protein beta/alpha.	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of 14-3-3 protein beta/alpha.	[14]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of 14-3-3 protein beta/alpha.	[18]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of 14-3-3 protein beta/alpha.	[19]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of 14-3-3 protein beta/alpha.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Flucloxacillin	DMNUWST	Approved	Flucloxacillin affects the binding of 14-3-3 protein beta/alpha.	[13]

1 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 14-3-3 protein beta/alpha.	[16]

References

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