Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG1V44F)

• DOT Name: ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1)
• Synonyms: ATP11 homolog
• Gene Name: ATPAF1
• Related Disease:
  Clear cell renal carcinoma
  Obesity
  Asthma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: ATPF1_HUMAN
• Pfam ID: PF06644
• Sequence:
  MAAVVVAAAGGAGPAVLQVAGLYRGLCAVRSRALGLGLVSPAQLRVFPVRPGSGRPEGGA
  DSSGVGAEAELQANPFYDRYRDKIQLLRRSDPAAFESRLEKRSEFRKQPVGHSRQGDFIK
  CVEQKTDALGKQSVNRGFTKDKTLSSIFNIEMVKEKTAEEIKQIWQQYFAAKDTVYAVIP
  AEKFDLIWNRAQSCPTFLCALPRREGYEFFVGQWTGTELHFTALINIQTRGEAAASQLIL
  YHYPELKEEKGIVLMTAEMDSTFLNVAEAQCIANQVQLFYATDRKETYGLVETFNLRPNE
  FKYMSVIAELEQSGLGAELKCAQNQNKT
• Function: May play an essential role for the assembly of the mitochondrial F1-F0 complex.
• Tissue Specificity: Weakly expressed in muscle.
• BioCyc Pathway: MetaCyc:ENSG00000123472-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[2]
Asthma	DISW9QNS	Limited	Genetic Variation	[3]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[4]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[4]

9 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 ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[13]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[14]

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 ATP synthase mitochondrial F1 complex assembly factor 1 (ATPAF1).	[8]

References

• [1] Systematic Analysis of the Expression of the Mitochondrial ATP Synthase (Complex V) Subunits in Clear Cell Renal Cell Carcinoma.Transl Oncol. 2017 Aug;10(4):661-668. doi: 10.1016/j.tranon.2017.06.002. Epub 2017 Jun 30.
• [2] Orchestrated downregulation of genes involved in oxidative metabolic pathways in obese vs. lean high-fat young male consumers.J Physiol Biochem. 2011 Mar;67(1):15-26. doi: 10.1007/s13105-010-0044-4. Epub 2010 Sep 30.
• [3] Identification of ATPAF1 as a novel candidate gene for asthma in children.J Allergy Clin Immunol. 2011 Oct;128(4):753-760.e11. doi: 10.1016/j.jaci.2011.04.058. Epub 2011 Jun 22.
• [4] A novel approach to identify driver genes involved in androgen-independent prostate cancer.Mol Cancer. 2014 May 23;13:120. doi: 10.1186/1476-4598-13-120.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.