Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT18H1B0)

• DOT Name: Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1)
• Synonyms: Eukaryotic peptide chain release factor subunit 3a; eRF3a; EC 3.6.5.-; G1 to S phase transition protein 1 homolog
• Gene Name: GSPT1
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cataract
  Colorectal carcinoma
  Hepatitis
  Hepatitis A virus infection
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Non-small-cell lung cancer
  Schizophrenia
  Testicular germ cell tumor
  Advanced cancer
  Gastric cancer
  Stomach cancer
  Gastric neoplasm
  Asthma
  Parkinson disease
• UniProt ID: ERF3A_HUMAN
• PDB ID: 3E1Y; 3J5Y; 3KUI; 4D61; 5HXB; 5LZT; 6XK9
• EC Number: 3.6.5.-
• Pfam ID: PF00009 ; PF03144 ; PF03143
• Sequence:
  MELSEPIVENGETEMSPEESWEHKEEISEAEPGGGSLGDGRPPEESAHEMMEEEEEIPKP
  KSVVAPPGAPKKEHVNVVFIGHVDAGKSTIGGQIMYLTGMVDKRTLEKYEREAKEKNRET
  WYLSWALDTNQEERDKGKTVEVGRAYFETEKKHFTILDAPGHKSFVPNMIGGASQADLAV
  LVISARKGEFETGFEKGGQTREHAMLAKTAGVKHLIVLINKMDDPTVNWSNERYEECKEK
  LVPFLKKVGFNPKKDIHFMPCSGLTGANLKEQSDFCPWYIGLPFIPYLDNLPNFNRSVDG
  PIRLPIVDKYKDMGTVVLGKLESGSICKGQQLVMMPNKHNVEVLGILSDDVETDTVAPGE
  NLKIRLKGIEEEEILPGFILCDPNNLCHSGRTFDAQIVIIEHKSIICPGYNAVLHIHTCI
  EEVEITALICLVDKKSGEKSKTRPRFVKQDQVCIARLRTAGTICLETFKDFPQMGRFTLR
  DEGKTIAIGKVLKLVPEKD
• Function: GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA. GSPT1/ERF3A mediates ETF1/ERF1 delivery to stop codons: The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site. GTP hydrolysis by GSPT1/ERF3A induces a conformational change that leads to its dissociation, permitting ETF1/ERF1 to accommodate fully in the A-site. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway:
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) (R-HSA-975956)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  Eukaryotic Translation Termination (R-HSA-72764)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Cataract	DISUD7SL	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Hepatitis	DISXXX35	Strong	Biomarker	[6]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Lung squamous cell carcinoma	DISXPIBD	Strong	Genetic Variation	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[9]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[10]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[11]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[12]
Gastric cancer	DISXGOUK	moderate	Biomarker	[13]
Stomach cancer	DISKIJSX	moderate	Biomarker	[13]
Gastric neoplasm	DISOKN4Y	Disputed	Biomarker	[14]
Asthma	DISW9QNS	Limited	Genetic Variation	[15]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[16]

19 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 Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[25]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[26]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[33]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[34]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[35]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[36]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[29]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1).	[30]

References

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