Details of Drug Off-Target (DOT)

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

• DOT Name: Actin-related protein 3C (ACTR3C)
• Synonyms: Actin-related protein 11
• Gene Name: ACTR3C
• Related Disease:
  Neoplasm
  Lung adenocarcinoma
• UniProt ID: ARP3C_HUMAN
• Pfam ID: PF00022
• Sequence:
  MFESFNVPGLYIAVQAVLALAASWTSRQVGERTLTGIVIDSGDGVTHVIPVAEGYVIGSC
  IKHIPIAGRDITYFIQQLLREREVGIPPEQSLETAKAIKEKYCYICPDIVKEFAKYDVDP
  QKWIKQYTGINAINQKKFVIDVGYERFLGPEIFFHPEFANPDSMESISDVVDEVIQNCPI
  DVRRPLYKMEQIPLSYPQGHGFHPLSPPFH
• Function: May play a role in the suppression of metastatic potential in lung adenoma carcinoma cells.
• Tissue Specificity: Expressed in kidney, stomach, spleen, bone marrow, uterus, testis, placenta, skeletal muscle, mammary gland, lung, fetal liver, and fetal kidney, but not detected in small intestine, brain, and thymus. Expressed in low-metastatic lung adenocarcinoma cells but not in high-metastatic ones.
• 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]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Actin-related protein 3C (ACTR3C).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Actin-related protein 3C (ACTR3C).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Actin-related protein 3C (ACTR3C).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Actin-related protein 3C (ACTR3C).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Actin-related protein 3C (ACTR3C).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Actin-related protein 3C (ACTR3C).	[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] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [7] 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.