Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVT4YA1)

• DOT Name: Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)
• Synonyms: ATG12-activating enzyme E1 ATG7; Autophagy-related protein 7; APG7-like; hAGP7; Ubiquitin-activating enzyme E1-like protein
• Gene Name: ATG7
• Related Disease: Spinocerebellar ataxia, autosomal recessive 31
• UniProt ID: ATG7_HUMAN
• Pfam ID: PF16420 ; PF00899
• Sequence:
  MAAATGDPGLSKLQFAPFSSALDVGFWHELTQKKLNEYRLDEAPKDIKGYYYNGDSAGLP
  ARLTLEFSAFDMSAPTPARCCPAIGTLYNTNTLESFKTADKKLLLEQAANEIWESIKSGT
  ALENPVLLNKFLLLTFADLKKYHFYYWFCYPALCLPESLPLIQGPVGLDQRFSLKQIEAL
  ECAYDNLCQTEGVTALPYFLIKYDENMVLVSLLKHYSDFFQGQRTKITIGVYDPCNLAQY
  PGWPLRNFLVLAAHRWSSSFQSVEVVCFRDRTMQGARDVAHSIIFEVKLPEMAFSPDCPK
  AVGWEKNQKGGMGPRMVNLSECMDPKRLAESSVDLNLKLMCWRLVPTLDLDKVVSVKCLL
  LGAGTLGCNVARTLMGWGVRHITFVDNAKISYSNPVRQPLYEFEDCLGGGKPKALAAADR
  LQKIFPGVNARGFNMSIPMPGHPVNFSSVTLEQARRDVEQLEQLIESHDVVFLLMDTRES
  RWLPAVIAASKRKLVINAALGFDTFVVMRHGLKKPKQQGAGDLCPNHPVASADLLGSSLF
  ANIPGYKLGCYFCNDVVAPGDSTRDRTLDQQCTVSRPGLAVIAGALAVELMVSVLQHPEG
  GYAIASSSDDRMNEPPTSLGLVPHQIRGFLSRFDNVLPVSLAFDKCTACSSKVLDQYERE
  GFNFLAKVFNSSHSFLEDLTGLTLLHQETQAAEIWDMSDDETI
• Function: E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Facilitates LC3-I lipidation with phosphatidylethanolamine to form LC3-II which is found on autophagosomal membranes. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Also plays a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner.
• Tissue Specificity: Widely expressed, especially in kidney, liver, lymph nodes and bone marrow.
• KEGG Pathway:
  Autophagy - other (hsa04136)
  Autophagy - animal (hsa04140)
  Ferroptosis (hsa04216)
  Neutrophil extracellular trap formation (hsa04613)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Antigen processing (R-HSA-983168)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spinocerebellar ataxia, autosomal recessive 31	DISQ05EW	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Beta-lapachone	DMMI84K	Phase 2	Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) affects the response to substance of Beta-lapachone.	[37]
Staurosporine	DM0E9BR	Investigative	Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) affects the response to substance of Staurosporine.	[38]

36 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 Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[15]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[16]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[2]
Atazanavir	DMSYRBX	Approved	Atazanavir increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[2]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[17]
Amsacrine	DMZKYIV	Approved	Amsacrine decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[18]
Promethazine	DM6I5GR	Approved	Promethazine decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[19]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[20]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[21]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[22]
CERC-801	DM3SZ7P	Phase 2	CERC-801 decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[24]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[25]
GSK618334	DMJPXZ4	Phase 1	GSK618334 increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[26]
AT7519	DMCE08M	Phase 1	AT7519 decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[27]
PMID26560530-Compound-35	DMO36RL	Patented	PMID26560530-Compound-35 increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[29]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[30]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[31]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[32]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[33]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[34]
Apigenin	DMI3491	Investigative	Apigenin increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[35]
Dorsomorphin	DMKYXJW	Investigative	Dorsomorphin increases the expression of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ubiquitin-like modifier-activating enzyme ATG7 (ATG7).	[7]

References

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