Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRF3E58)

• DOT Name: Actin-related protein 10 (ACTR10)
• Synonyms: Actin-related protein 11; hARP11
• Gene Name: ACTR10
• Related Disease:
  Neoplasm
  Lung adenocarcinoma
• UniProt ID: ARP10_HUMAN
• Pfam ID: PF00022
• Sequence:
  MPLYEGLGSGGEKTAVVIDLGEAFTKCGFAGETGPRCIIPSVIKRAGMPKPVRVVQYNIN
  TEELYSYLKEFIHILYFRHLLVNPRDRRVVIIESVLCPSHFRETLTRVLFKYFEVPSVLL
  APSHLMALLTLGINSAMVLDCGYRESLVLPIYEGIPVLNCWGALPLGGKALHKELETQLL
  EQCTVDTSVAKEQSLPSVMGSVPEGVLEDIKARTCFVSDLKRGLKIQAAKFNIDGNNERP
  SPPPNVDYPLDGEKILHILGSIRDSVVEILFEQDNEEQSVATLILDSLIQCPIDTRKQLA
  ENLVVIGGTSMLPGFLHRLLAEIRYLVEKPKYKKALGTKTFRIHTPPAKANCVAWLGGAI
  FGALQDILGSRSVSKEYYNQTGRIPDWCSLNNPPLEMMFDVGKTQPPLMKRAFSTEK
• Function: Part of the dynactin complex that 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:
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  Neutrophil degranulation (R-HSA-6798695)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
  MHC class II antigen presentation (R-HSA-2132295)

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]

6 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 10 (ACTR10).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Actin-related protein 10 (ACTR10).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Actin-related protein 10 (ACTR10).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Actin-related protein 10 (ACTR10).	[5]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Actin-related protein 10 (ACTR10).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Actin-related protein 10 (ACTR10).	[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] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] 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.
• [6] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.