Details of Drug Off-Target (DOT)

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

• DOT Name: Actin-related protein 2/3 complex subunit 1A (ARPC1A)
• Synonyms: SOP2-like protein
• Gene Name: ARPC1A
• Related Disease:
  Rheumatoid arthritis
  Acute coronary syndrome
  Bone osteosarcoma
  Osteosarcoma
  Pancreatic cancer
  Pancreatic tumour
  Plasma cell myeloma
• UniProt ID: ARC1A_HUMAN
• PDB ID: 6YW7
• Pfam ID: PF00400
• Sequence:
  MSLHQFLLEPITCHAWNRDRTQIALSPNNHEVHIYKKNGSQWVKAHELKEHNGHITGIDW
  APKSDRIVTCGADRNAYVWSQKDGVWKPTLVILRINRAATFVKWSPLENKFAVGSGARLI
  SVCYFESENDWWVSKHIKKPIRSTVLSLDWHPNNVLLAAGSCDFKCRVFSAYIKEVDEKP
  ASTPWGSKMPFGQLMSEFGGSGTGGWVHGVSFSASGSRLAWVSHDSTVSVADASKSVQVS
  TLKTEFLPLLSVSFVSENSVVAAGHDCCPMLFNYDDRGCLTFVSKLDIPKQSIQRNMSAM
  ERFRNMDKRATTEDRNTALETLHQNSITQVSIYEVDKQDCRKFCTTGIDGAMTIWDFKTL
  ESSIQGLRIM
• Function: Probably functions as a 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.
• 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)
  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
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[1]
Acute coronary syndrome	DIS7DYEW	Strong	Genetic Variation	[2]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	Strong	Biomarker	[4]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[4]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Brilinta	DMBR01X	Approved	Actin-related protein 2/3 complex subunit 1A (ARPC1A) increases the Acute coronary syndrome ADR of Brilinta.	[2]

11 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 1A (ARPC1A).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Actin-related protein 2/3 complex subunit 1A (ARPC1A).	[15]

References

• [1] Contribution of Genetic Factors to Lower DHEAS in Patients with Rheumatoid Arthritis.Cell Mol Neurobiol. 2018 Jan;38(1):379-383. doi: 10.1007/s10571-017-0522-0. Epub 2017 Jul 15.
• [2] Effect of genetic variations on ticagrelor plasma levels and clinical outcomes. Eur Heart J. 2015 Aug 1;36(29):1901-12.
• [3] Expression of miR?42?p in osteosarcoma with miRNA microarray data, and its potential signaling pathways.Mol Med Rep. 2019 Feb;19(2):974-983. doi: 10.3892/mmr.2018.9761. Epub 2018 Dec 13.
• [4] Characterization of the 7q21-q22 amplicon identifies ARPC1A, a subunit of the Arp2/3 complex, as a regulator of cell migration and invasion in pancreatic cancer.Genes Chromosomes Cancer. 2009 Apr;48(4):330-9. doi: 10.1002/gcc.20643.
• [5] Differential expression of serum proteins in multiple myeloma.Exp Ther Med. 2019 Jan;17(1):649-656. doi: 10.3892/etm.2018.7010. Epub 2018 Nov 23.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):117-27.
• [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] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] Effect of genetic variations on ticagrelor plasma levels and clinical outcomes. Eur Heart J. 2015 Aug 1;36(29):1901-12.