Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ9VV5T)

• DOT Name: AFG1-like ATPase (AFG1L)
• Synonyms: Lactation elevated protein 1; EC 3.6.-.-; Protein AFG1 homolog
• Gene Name: AFG1L
• Related Disease: Bipolar disorder
• UniProt ID: AFG1L_HUMAN
• EC Number: 3.6.-.-
• Pfam ID: PF03969
• Sequence:
  MAASWSLLVTLRPLAQSPLRGRCVGCGAWAAALAPLATAPGKPFWKAYTVQTSESMTPTA
  TSETYLKALAVCHGPLDHYDFLIKAHELKDDEHQRRVIQCLQKLHEDLKGYNIEAEGLFS
  KLFSRSKPPRGLYVYGDVGTGKTMVMDMFYAYVEMKRKKRVHFHGFMLDVHKRIHRLKQS
  LPKRKPGFMAKSYDPIAPIAEEISEEACLLCFDEFQVTDIADAMILKQLFENLFKNGVVV
  VATSNRPPEDLYKNGLQRANFVPFIAVLKEYCNTVQLDSGIDYRKRELPAAGKLYYLTSE
  ADVEAVMDKLFDELAQKQNDLTRPRILKVQGRELRLNKACGTVADCTFEELCERPLGASD
  YLELSKNFDTIFLRNIPQFTLANRTQGRRFITLIDNFYDLKVRIICSASTPISSLFLHQH
  HDSELEQSRILMDDLGLSQDSAEGLSMFTGEEEIFAFQRTISRLTEMQTEQYWNEGDRTK
  K
• Function: Putative mitochondrial ATPase. Plays a role in mitochondrial morphology and mitochondrial protein metabolism. Promotes degradation of excess nuclear-encoded complex IV subunits (COX4I1, COX5A and COX6A1) and normal activity of complexes III and IV of the respiratory chain. Mediates mitochondrial translocation of TP53 and its transcription-independent apoptosis in response to genotoxic stress.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of AFG1-like ATPase (AFG1L).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of AFG1-like ATPase (AFG1L).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of AFG1-like ATPase (AFG1L).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of AFG1-like ATPase (AFG1L).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of AFG1-like ATPase (AFG1L).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of AFG1-like ATPase (AFG1L).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of AFG1-like ATPase (AFG1L).	[3]

References

• [1] An investigation of candidate regions for association with bipolar disorder.Am J Med Genet B Neuropsychiatr Genet. 2010 Oct 5;153B(7):1292-7. doi: 10.1002/ajmg.b.31100.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [6] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.