Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1QAU16)

• DOT Name: Alpha-centractin (ACTR1A)
• Synonyms: Centractin; ARP1; Actin-RPV; Centrosome-associated actin homolog
• Gene Name: ACTR1A
• Related Disease:
  Acute leukaemia
  Choriocarcinoma
  Hepatocellular carcinoma
  Immunodeficiency
  Plasma cell myeloma
  Spinocerebellar ataxia type 5
  Allergic rhinitis
  Ulcerative colitis
  Mesothelioma
• UniProt ID: ACTZ_HUMAN
• Pfam ID: PF00022
• Sequence:
  MESYDVIANQPVVIDNGSGVIKAGFAGDQIPKYCFPNYVGRPKHVRVMAGALEGDIFIGP
  KAEEHRGLLSIRYPMEHGIVKDWNDMERIWQYVYSKDQLQTFSEEHPVLLTEAPLNPRKN
  RERAAEVFFETFNVPALFISMQAVLSLYATGRTTGVVLDSGDGVTHAVPIYEGFAMPHSI
  MRIDIAGRDVSRFLRLYLRKEGYDFHSSSEFEIVKAIKERACYLSINPQKDETLETEKAQ
  YYLPDGSTIEIGPSRFRAPELLFRPDLIGEESEGIHEVLVFAIQKSDMDLRRTLFSNIVL
  SGGSTLFKGFGDRLLSEVKKLAPKDVKIRISAPQERLYSTWIGGSILASLDTFKKMWVSK
  KEYEEDGARSIHRKTF
• Function: Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
  AURKA Activation by TPX2 (R-HSA-8854518)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[1]
Choriocarcinoma	DISDBVNL	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Immunodeficiency	DIS093I0	Strong	Biomarker	[4]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[5]
Spinocerebellar ataxia type 5	DISPYXJ0	Strong	Genetic Variation	[6]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[7]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[8]
Mesothelioma	DISKWK9M	Limited	Genetic Variation	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Alpha-centractin (ACTR1A) affects the response to substance of Methotrexate.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Alpha-centractin (ACTR1A).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-centractin (ACTR1A).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Alpha-centractin (ACTR1A).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Alpha-centractin (ACTR1A).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-centractin (ACTR1A).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Alpha-centractin (ACTR1A).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Alpha-centractin (ACTR1A).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Alpha-centractin (ACTR1A).	[17]
Selenium	DM25CGV	Approved	Selenium increases the expression of Alpha-centractin (ACTR1A).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Alpha-centractin (ACTR1A).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alpha-centractin (ACTR1A).	[19]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Alpha-centractin (ACTR1A).	[16]

References

• [1] Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene.Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4573-8. doi: 10.1073/pnas.95.8.4573.
• [2] The ARP-1 orphan receptor represses steroid-mediated stimulation of human placental lactogen gene expression.J Mol Endocrinol. 1996 Jun;16(3):221-7. doi: 10.1677/jme.0.0160221.
• [3] Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXR alpha and retinoic acid.Mol Cell Biol. 1992 Aug;12(8):3380-9. doi: 10.1128/mcb.12.8.3380-3389.1992.
• [4] Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.J Clin Invest. 2013 Sep;123(9):3829-38. doi: 10.1172/JCI70266. Epub 2013 Aug 8.
• [5] DCZ0814 induces apoptosis and G0/G1 phase cell cycle arrest in myeloma by dual inhibition of mTORC1/2.Cancer Manag Res. 2019 May 27;11:4797-4808. doi: 10.2147/CMAR.S194202. eCollection 2019.
• [6] Beta-III spectrin mutation L253P associated with spinocerebellar ataxia type 5 interferes with binding to Arp1 and protein trafficking from the Golgi.Hum Mol Genet. 2010 Sep 15;19(18):3634-41. doi: 10.1093/hmg/ddq279. Epub 2010 Jul 5.
• [7] Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nat Genet. 2018 Aug;50(8):1072-1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16.
• [8] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [9] Transcriptome sequencing of malignant pleural mesothelioma tumors.Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3521-6. doi: 10.1073/pnas.0712399105. Epub 2008 Feb 26.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [17] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [18] 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.
• [19] 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.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.