Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ96STE)

• DOT Name: Coatomer subunit delta (ARCN1)
• Synonyms: Archain; Delta-coat protein; Delta-COP
• Gene Name: ARCN1
• Related Disease:
  Glioma
  Sensory ataxia
  Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay
• UniProt ID: COPD_HUMAN
• Pfam ID: PF00928 ; PF01217
• Sequence:
  MVLLAAAVCTKAGKAIVSRQFVEMTRTRIEGLLAAFPKLMNTGKQHTFVETESVRYVYQP
  MEKLYMVLITTKNSNILEDLETLRLFSRVIPEYCRALEENEISEHCFDLIFAFDEIVALG
  YRENVNLAQIRTFTEMDSHEEKVFRAVRETQEREAKAEMRRKAKELQQARRDAERQGKKA
  PGFGGFGSSAVSGGSTAAMITETIIETDKPKVAPAPARPSGPSKALKLGAKGKEVDNFVD
  KLKSEGETIMSSSMGKRTSEATKMHAPPINMESVHMKIEEKITLTCGRDGGLQNMELHGM
  IMLRISDDKYGRIRLHVENEDKKGVQLQTHPNVDKKLFTAESLIGLKNPEKSFPVNSDVG
  VLKWRLQTTEESFIPLTINCWPSESGNGCDVNIEYELQEDNLELNDVVITIPLPSGVGAP
  VIGEIDGEYRHDSRRNTLEWCLPVIDAKNKSGSLEFSIAGQPNDFFPVQVSFVSKKNYCN
  IQVTKVTQVDGNSPVRFSTETTFLVDKYEIL
• Function: Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway:
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Genetic Variation	[1]
Sensory ataxia	DISSMCYQ	Strong	Biomarker	[2]
Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay	DISN208Z	Strong	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Coatomer subunit delta (ARCN1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coatomer subunit delta (ARCN1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coatomer subunit delta (ARCN1).	[6]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Coatomer subunit delta (ARCN1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Coatomer subunit delta (ARCN1).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Coatomer subunit delta (ARCN1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Coatomer subunit delta (ARCN1).	[10]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Coatomer subunit delta (ARCN1).	[11]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Coatomer subunit delta (ARCN1).	[12]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine affects the localization of Coatomer subunit delta (ARCN1).	[8]

References

• [1] Fine mapping of a region of chromosome 11q23.3 reveals independent locus associated with risk of glioma.PLoS One. 2012;7(12):e52864. doi: 10.1371/journal.pone.0052864. Epub 2012 Dec 31.
• [2] Mutation in archain 1, a subunit of COPI coatomer complex, causes diluted coat color and Purkinje cell degeneration.PLoS Genet. 2010 May 20;6(5):e1000956. doi: 10.1371/journal.pgen.1000956.
• [3] ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects. Am J Hum Genet. 2016 Aug 4;99(2):451-9. doi: 10.1016/j.ajhg.2016.06.011. Epub 2016 Jul 28.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] 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.
• [6] 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.
• [7] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [8] Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018;14(8):1435-1455. doi: 10.1080/15548627.2018.1474314. Epub 2018 Jul 20.
• [9] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [10] 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.
• [11] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [12] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.