Details of Drug Off-Target (DOT)

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

• DOT Name: Arrestin domain-containing protein 1 (ARRDC1)
• Synonyms: Alpha-arrestin 1
• Gene Name: ARRDC1
• Related Disease:
  Clear cell renal carcinoma
  Neoplasm
  Renal cell carcinoma
  Asthma
• UniProt ID: ARRD1_HUMAN
• Pfam ID: PF02752 ; PF00339
• Sequence:
  MGRVQLFEISLSHGRVVYSPGEPLAGTVRVRLGAPLPFRAIRVTCIGSCGVSNKANDTAW
  VVEEGYFNSSLSLADKGSLPAGEHSFPFQFLLPATAPTSFEGPFGKIVHQVRAAIHTPRF
  SKDHKCSLVFYILSPLNLNSIPDIEQPNVASATKKFSYKLVKTGSVVLTASTDLRGYVVG
  QALQLHADVENQSGKDTSPVVASLLQKVSYKAKRWIHDVRTIAEVEGAGVKAWRRAQWHE
  QILVPALPQSALPGCSLIHIDYYLQVSLKAPEATVTLPVFIGNIAVNHAPVSPRPGLGLP
  PGAPPLVVPSAPPQEEAEAEAAAGGPHFLDPVFLSTKSHSQRQPLLATLSSVPGAPEPCP
  QDGSPASHPLHPPLCISTGATVPYFAEGSGGPVPTTSTLILPPEYSSWGYPYEAPPSYEQ
  SCGGVEPSLTPES
• Function: Functions as an adapter recruiting ubiquitin-protein ligases to their specific substrates. Through an ubiquitination-dependent mechanism plays for instance a role in the incorporation of SLC11A2 into extracellular vesicles. More generally, plays a role in the extracellular transport of proteins between cells through the release in the extracellular space of microvesicles. By participating in the ITCH-mediated ubiquitination and subsequent degradation of NOTCH1, negatively regulates the NOTCH signaling pathway.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[1]
Asthma	DISW9QNS	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Arrestin domain-containing protein 1 (ARRDC1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Arrestin domain-containing protein 1 (ARRDC1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Arrestin domain-containing protein 1 (ARRDC1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Arrestin domain-containing protein 1 (ARRDC1).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Arrestin domain-containing protein 1 (ARRDC1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Arrestin domain-containing protein 1 (ARRDC1).	[8]

References

• [1] ARRDC1 and ARRDC3 act as tumor suppressors in renal cell carcinoma by facilitating YAP1 degradation.Am J Cancer Res. 2018 Jan 1;8(1):132-143. eCollection 2018.
• [2] Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies.Lancet Respir Med. 2019 Jun;7(6):509-522. doi: 10.1016/S2213-2600(19)30055-4. Epub 2019 Apr 27.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [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.
• [8] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.