Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHBPF1Z)

• DOT Name: Ezrin (EZR)
• Synonyms: Cytovillin; Villin-2; p81
• Gene Name: EZR
• Related Disease: Autosomal recessive non-syndromic intellectual disability
• UniProt ID: EZRI_HUMAN
• PDB ID: 1NI2; 4RM8; 4RM9; 4RMA; 7T1K; 7T1L
• Pfam ID: PF00769 ; PF20492 ; PF09380 ; PF00373 ; PF09379
• Sequence:
  MPKPINVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLHYVDNKGFPTWLK
  LDKKVSAQEVRKENPLQFKFRAKFYPEDVAEELIQDITQKLFFLQVKEGILSDEIYCPPE
  TAVLLGSYAVQAKFGDYNKEVHKSGYLSSERLIPQRVMDQHKLTRDQWEDRIQVWHAEHR
  GMLKDNAMLEYLKIAQDLEMYGINYFEIKNKKGTDLWLGVDALGLNIYEKDDKLTPKIGF
  PWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKRILQLCMGNHELYMRRRKPDTI
  EVQQMKAQAREEKHQKQLERQQLETEKKRRETVEREKEQMMREKEELMLRLQDYEEKTKK
  AERELSEQIQRALQLEEERKRAQEEAERLEADRMAALRAKEELERQAVDQIKSQEQLAAE
  LAEYTAKIALLEEARRRKEDEVEEWQHRAKEAQDDLVKTKEELHLVMTAPPPPPPPVYEP
  VSYHVQESLQDEGAEPTGYSAELSSEGIRDDRNEEKRITEAEKNERVQRQLLTLSSELSQ
  ARDENKRTHNDIIHNENMRQGRDKYKTLRQIRQGNTKQRIDEFEAL
• Function: Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis.
• Tissue Specificity: Expressed in cerebral cortex, basal ganglia, hippocampus, hypophysis, and optic nerve. Weakly expressed in brain stem and diencephalon. Stronger expression was detected in gray matter of frontal lobe compared to white matter (at protein level). Component of the microvilli of intestinal epithelial cells. Preferentially expressed in astrocytes of hippocampus, frontal cortex, thalamus, parahippocampal cortex, amygdala, insula, and corpus callosum. Not detected in neurons in most tissues studied.
• KEGG Pathway:
  Tight junction (hsa04530)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Gastric acid secretion (hsa04971)
  Pathogenic Escherichia coli infection (hsa05130)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  Recycling pathway of L1 (R-HSA-437239)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Netrin-1 signaling (R-HSA-373752)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ezrin (EZR).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ezrin (EZR).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ezrin (EZR).	[32]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the phosphorylation of Ezrin (EZR).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ezrin (EZR).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ezrin (EZR).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ezrin (EZR).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ezrin (EZR).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ezrin (EZR).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ezrin (EZR).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ezrin (EZR).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ezrin (EZR).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ezrin (EZR).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ezrin (EZR).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ezrin (EZR).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ezrin (EZR).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ezrin (EZR).	[16]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ezrin (EZR).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ezrin (EZR).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ezrin (EZR).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ezrin (EZR).	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Ezrin (EZR).	[20]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Ezrin (EZR).	[21]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ezrin (EZR).	[22]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Ezrin (EZR).	[23]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ezrin (EZR).	[24]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Ezrin (EZR).	[25]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Ezrin (EZR).	[21]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Ezrin (EZR).	[20]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Ezrin (EZR).	[26]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Ezrin (EZR).	[20]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Ezrin (EZR).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ezrin (EZR).	[27]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ezrin (EZR).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ezrin (EZR).	[19]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Ezrin (EZR).	[29]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ezrin (EZR).	[17]
CXL	DM3JFZ2	Phase 2	CXL increases the expression of Ezrin (EZR).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ezrin (EZR).	[25]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ezrin (EZR).	[31]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Ezrin (EZR).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ezrin (EZR).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ezrin (EZR).	[35]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Ezrin (EZR).	[36]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Ezrin (EZR).	[37]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Ezrin (EZR).	[38]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Ezrin (EZR).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Ezrin (EZR).	[30]

References

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