Details of Drug Off-Target (DOT)

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

• DOT Name: Actin-related protein 2/3 complex subunit 5 (ARPC5)
• Synonyms: Arp2/3 complex 16 kDa subunit; p16-ARC
• Gene Name: ARPC5
• Related Disease:
  Advanced cancer
  Congenital hypothyroidism
  Head-neck squamous cell carcinoma
  Lung squamous cell carcinoma
  Periodontal disease
  Plasma cell myeloma
  Rhabdomyosarcoma
• UniProt ID: ARPC5_HUMAN
• PDB ID: 6UHC; 6YW7
• Pfam ID: PF04699
• Sequence:
  MSKNTVSSARFRKVDVDEYDENKFVDEEDGGDGQAGPDEGEVDSCLRQGNMTAALQAALK
  NPPINTKSQAVKDRAGSIVLKVLISFKANDIEKAVQSLDKNGVDLLMKYIYKGFESPSDN
  SSAMLLQWHEKALAAGGVGSIVRVLTARKTV
• Function: Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).
• 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)
• Reactome Pathway:
  EPHB-mediated forward signaling (R-HSA-3928662)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  Neutrophil degranulation (R-HSA-6798695)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)

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]
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[1]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[3]
Periodontal disease	DISJQHVN	Strong	Biomarker	[4]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[5]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[6]

10 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 Actin-related protein 2/3 complex subunit 5 (ARPC5).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[12]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[13]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus increases the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Actin-related protein 2/3 complex subunit 5 (ARPC5).	[16]

References

• [1] Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma.Int J Oncol. 2012 Jun;40(6):1770-8. doi: 10.3892/ijo.2012.1390. Epub 2012 Feb 29.
• [2] Effects of hypothyroidism on expression of CRMP2B and ARPC5 during development of the rat frontal cortex.Int J Biol Sci. 2013;9(2):209-18. doi: 10.7150/ijbs.5646. Epub 2013 Feb 12.
• [3] Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma.J Hum Genet. 2012 Jan;57(1):38-45. doi: 10.1038/jhg.2011.126. Epub 2011 Nov 17.
• [4] Targeted Proteomics Guided by Label-free Quantitative Proteome Analysis in Saliva Reveal Transition Signatures from Health to Periodontal Disease.Mol Cell Proteomics. 2018 Jul;17(7):1392-1409. doi: 10.1074/mcp.RA118.000718. Epub 2018 Apr 2.
• [5] The Expression of Actin-Related Protein 2/3 Complex Subunit 5 (ARPC5) Expression in Multiple Myeloma and its Prognostic Significance.Med Sci Monit. 2018 Sep 11;24:6340-6348. doi: 10.12659/MSM.908944.
• [6] The essential role of clathrin-mediated endocytosis in the infectious entry of human enterovirus 71.J Biol Chem. 2011 Jan 7;286(1):309-21. doi: 10.1074/jbc.M110.168468. Epub 2010 Oct 18.
• [7] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] 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.
• [13] Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells. Biol Pharm Bull. 2007 Feb;30(2):247-53. doi: 10.1248/bpb.30.247.
• [14] Calcineurin is an important factor involved in glucose uptake in human adipocytes. Mol Cell Biochem. 2018 Aug;445(1-2):157-168. doi: 10.1007/s11010-017-3261-0. Epub 2018 Jan 27.
• [15] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.