Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNEC9UT)

• DOT Name: Actin-related protein 3B (ACTR3B)
• Synonyms: ARP3-beta; Actin-like protein 3B; Actin-related protein ARP4
• Gene Name: ACTR3B
• Related Disease:
  Neoplasm
  Lung adenocarcinoma
• UniProt ID: ARP3B_HUMAN
• Pfam ID: PF00022
• Sequence:
  MAGSLPPCVVDCGTGYTKLGYAGNTEPQFIIPSCIAIRESAKVVDQAQRRVLRGVDDLDF
  FIGDEAIDKPTYATKWPIRHGIIEDWDLMERFMEQVVFKYLRAEPEDHYFLMTEPPLNTP
  ENREYLAEIMFESFNVPGLYIAVQAVLALAASWTSRQVGERTLTGIVIDSGDGVTHVIPV
  AEGYVIGSCIKHIPIAGRDITYFIQQLLREREVGIPPEQSLETAKAIKEKYCYICPDIVK
  EFAKYDVDPRKWIKQYTGINAINQKKFVIDVGYERFLGPEIFFHPEFANPDFMESISDVV
  DEVIQNCPIDVRRPLYKNVVLSGGSTMFRDFGRRLQRDLKRVVDARLRLSEELSGGRIKP
  KPVEVQVVTHHMQRYAVWFGGSMLASTPEFFQVCHTKKDYEEYGPSICRHNPVFGVMS
• Function: Plays a role in the organization of the actin cytoskeleton. May function as ATP-binding component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. May decrease the metastatic potential of tumors.
• Tissue Specificity: Detected in fetal brain. Detected throughout the adult brain, in neurons from gray matter, but not in white matter. Detected in liver, skeletal muscle and pancreas. Detected in lung adenocarcinoma cells with low metastatic potential, but not in lung adenocarcinoma cells with high metastatic potential.
• KEGG Pathway:
  Endocytosis (hsa04144)
  Tight junction (hsa04530)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Regulation of actin cytoskeleton (hsa04810)
  Bacterial invasion of epithelial cells (hsa05100)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Yersinia infection (hsa05135)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Actin-related protein 3B (ACTR3B).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Actin-related protein 3B (ACTR3B).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Actin-related protein 3B (ACTR3B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Actin-related protein 3B (ACTR3B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Actin-related protein 3B (ACTR3B).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Actin-related protein 3B (ACTR3B).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Actin-related protein 3B (ACTR3B).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Actin-related protein 3B (ACTR3B).	[7]

References

• [1] Expression of the Arp11 gene suppresses the tumorigenicity of PC-14 human lung adenocarcinoma cells.Biochem Biophys Res Commun. 2003 Dec 26;312(4):889-96. doi: 10.1016/j.bbrc.2003.10.200.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] 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.