Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ8DJX5)

• DOT Name: Eukaryotic translation initiation factor 5A-1 (EIF5A)
• Synonyms: eIF-5A-1; eIF-5A1; Eukaryotic initiation factor 5A isoform 1; eIF-5A; Rev-binding factor; eIF-4D
• Gene Name: EIF5A
• Related Disease: Faundes-Banka syndrome
• UniProt ID: IF5A1_HUMAN
• PDB ID: 3CPF; 5DLQ; 8A0E
• Pfam ID: PF01287 ; PF21485
• Sequence:
  MADDLDFETGDAGASATFPMQCSALRKNGFVVLKGRPCKIVEMSTSKTGKHGHAKVHLVG
  IDIFTGKKYEDICPSTHNMDVPNIKRNDFQLIGIQDGYLSLLQDSGEVREDLRLPEGDLG
  KEIEQKYDCGEEILITVLSAMTEEAAVAIKAMAK
• Function: Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts. Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome. Acts as a ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step. Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis. Regulates also TNF-alpha-mediated apoptosis. Mediates effects of polyamines on neuronal process extension and survival. Is required for autophagy by assisting the ribosome in translating the ATG3 protein at a specific amino acid sequence, the 'ASP-ASP-Gly' motif, leading to the increase of the efficiency of ATG3 translation and facilitation of LC3B lipidation and autophagosome formation ; (Microbial infection) Cellular cofactor of human T-cell leukemia virus type I (HTLV-1) Rex protein and of human immunodeficiency virus type 1 (HIV-1) Rev protein, essential for mRNA export of retroviral transcripts.
• Tissue Specificity: Expressed in umbilical vein endothelial cells and several cancer cell lines (at protein level).
• Reactome Pathway: Hypusine synthesis from eIF5A-lysine (R-HSA-204626)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Faundes-Banka syndrome	DISRQ7DP	Strong	Autosomal dominant	[1]

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Eukaryotic translation initiation factor 5A-1 (EIF5A) increases the response to substance of Arsenic.	[25]
Methotrexate	DM2TEOL	Approved	Eukaryotic translation initiation factor 5A-1 (EIF5A) affects the response to substance of Methotrexate.	[26]
Paclitaxel	DMLB81S	Approved	Eukaryotic translation initiation factor 5A-1 (EIF5A) increases the response to substance of Paclitaxel.	[27]
Topotecan	DMP6G8T	Approved	Eukaryotic translation initiation factor 5A-1 (EIF5A) affects the response to substance of Topotecan.	[26]
Mitoxantrone	DMM39BF	Approved	Eukaryotic translation initiation factor 5A-1 (EIF5A) affects the response to substance of Mitoxantrone.	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	Eukaryotic translation initiation factor 5A-1 (EIF5A) affects the response to substance of THAPSIGARGIN.	[28]
Sulforaphane	DMQY3L0	Investigative	Eukaryotic translation initiation factor 5A-1 (EIF5A) affects the binding of Sulforaphane.	[29]

22 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 translation initiation factor 5A-1 (EIF5A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[10]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[11]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[12]
Morphine	DMRMS0L	Approved	Morphine increases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[13]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[14]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[23]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the acetylation of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Eukaryotic translation initiation factor 5A-1 (EIF5A).	[22]

References

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