Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL508AF)

• DOT Name: ATPase family AAA domain-containing protein 3B (ATAD3B)
• Synonyms: AAA-TOB3
• Gene Name: ATAD3B
• Related Disease:
  Advanced cancer
  Astrocytoma
  Carcinoma
  Lung adenocarcinoma
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: ATD3B_HUMAN
• Pfam ID: PF00004 ; PF12037
• Sequence:
  MSWLFGVNKGPKGEGAGPPPPLPPAQPGAEGGGDRGLGDRPAPKDKWSNFDPTGLERAAK
  AARELEHSRYAKEALNLAQMQEQTLQLEQQSKLKEYEAAVEQLKSEQIRAQAEERRKTLS
  EETRQHQARAQYQDKLARQRYEDQLKQQQLLNEENLRKQEESVQKQEAMRRATVEREMEL
  RHKNEMLRVETEARARAKAERENADIIREQIRLKASEHRQTVLESIRTAGTLFGEGFRAF
  VTDRDKVTATVAGLTLLAVGVYSAKNATAVTGRFIEARLGKPSLVRETSRITVLEALRHP
  IQVSRRLLSRPQDVLEGVVLSPSLEARVRDIAIATRNTKKNRGLYRHILLYGPPGTGKTL
  FAKKLALHSGMDYAIMTGGDVAPMGREGVTAMHKLFDWANTSRRGLLLFMDEADAFLRKR
  ATEEISKDLRATLNAFLYHMGQHSNKFMLVLASNLPEQFDCAINSRIDVMVHFDLPQQEE
  RERLVRLHFDNCVLKPATEGKRRLKLAQFDYGRKCSEVARLTEGMSGREIAQLAVSWQAT
  AYASKDGVLTEAMMDACVQDAVQQYRQKMRWLKAEGPGRGVEHPLSGVQGETLTSWSLAT
  DPSYPCLAGPCTFRICSWMGTGLCPGPLSPRMSCGGGRPFCPPGHPLL
• Function: May play a role in a mitochondrial network organization typical for stem cells, characterized by reduced mitochondrial metabolism, low mtDNA copies and fragmentated mitochondrial network. may act by suppressing ATAD3A function, interfering with ATAD3A interaction with matrix nucleoid complexes.
• Tissue Specificity: Tends to be down-regulated in differentiated cells and re-expressed in pluripotent stem cells or cancer cells (at protein level).
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Astrocytoma	DISL3V18	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]
Neoplasm	DISZKGEW	moderate	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of ATPase family AAA domain-containing protein 3B (ATAD3B).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of ATPase family AAA domain-containing protein 3B (ATAD3B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATPase family AAA domain-containing protein 3B (ATAD3B).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATPase family AAA domain-containing protein 3B (ATAD3B).	[8]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of ATPase family AAA domain-containing protein 3B (ATAD3B).	[10]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of ATPase family AAA domain-containing protein 3B (ATAD3B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATPase family AAA domain-containing protein 3B (ATAD3B).	[13]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of ATPase family AAA domain-containing protein 3B (ATAD3B).	[11]

References

• [1] ATAD3, a vital membrane bound mitochondrial ATPase involved in tumor progression.J Bioenerg Biomembr. 2012 Feb;44(1):189-97. doi: 10.1007/s10863-012-9424-5.
• [2] ATAD 3A and ATAD 3B are distal 1p-located genes differentially expressed in human glioma cell lines and present in vitro anti-oncogenic and chemoresistant properties.Exp Cell Res. 2008 Sep 10;314(15):2870-83. doi: 10.1016/j.yexcr.2008.06.017. Epub 2008 Jul 1.
• [3] Molecular characterization of the tumor-associated antigen AAA-TOB3.Cell Mol Life Sci. 2006 Sep;63(18):2162-74. doi: 10.1007/s00018-006-6200-x.
• [4] Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.Int J Biol Markers. 2017 Jul 24;32(3):e325-e332. doi: 10.5301/ijbm.5000275.
• [5] Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.PLoS Comput Biol. 2013;9(6):e1003100. doi: 10.1371/journal.pcbi.1003100. Epub 2013 Jun 20.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [12] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.