Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3ZT7D)

• DOT Name: Exocyst complex component 8 (EXOC8)
• Synonyms: Exocyst complex 84 kDa subunit
• Gene Name: EXOC8
• Related Disease: Neurodevelopmental disorder with microcephaly, seizures, and brain atrophy
• UniProt ID: EXOC8_HUMAN
• Pfam ID: PF16528 ; PF08700
• Sequence:
  MAMAMSDSGASRLRRQLESGGFEARLYVKQLSQQSDGDRDLQEHRQRIQALAEETAQNLK
  RNVYQNYRQFIETAREISYLESEMYQLSHLLTEQKSSLESIPLTLLPAAAAAGAAAASGG
  EEGVGGAGGRDHLRGQAGFFSTPGGASRDGSGPGEEGKQRTLTTLLEKVEGCRHLLETPG
  QYLVYNGDLVEYDADHMAQLQRVHGFLMNDCLLVATWLPQRRGMYRYNALYSLDGLAVVN
  VKDNPPMKDMFKLLMFPESRIFQAENAKIKREWLEVLEDTKRALSEKRRREQEEAAAPRG
  PPQVTSKATNPFEDDEEEEPAVPEVEEEKVDLSMEWIQELPEDLDVCIAQRDFEGAVDLL
  DKLNHYLEDKPSPPPVKELRAKVEERVRQLTEVLVFELSPDRSLRGGPKATRRAVSQLIR
  LGQCTKACELFLRNRAAAVHTAIRQLRIEGATLLYIHKLCHVFFTSLLETAREFEIDFAG
  TDSGCYSAFVVWARSAMGMFVDAFSKQVFDSKESLSTAAECVKVAKEHCQQLGDIGLDLT
  FIIHALLVKDIQGALHSYKEIIIEATKHRNSEEMWRRMNLMTPEALGKLKEEMKSCGVSN
  FEQYTGDDCWVNLSYTVVAFTKQTMGFLEEALKLYFPELHMVLLESLVEIILVAVQHVDY
  SLRCEQDPEKKAFIRQNASFLYETVLPVVEKRFEEGVGKPAKQLQDLRNASRLIRVNPES
  TTSVV
• Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
• Reactome Pathway:
  Insulin processing (R-HSA-264876)
  VxPx cargo-targeting to cilium (R-HSA-5620916)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurodevelopmental disorder with microcephaly, seizures, and brain atrophy	DISRTTRZ	Strong	Autosomal recessive	[1]

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 Exocyst complex component 8 (EXOC8).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Exocyst complex component 8 (EXOC8).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Exocyst complex component 8 (EXOC8).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Exocyst complex component 8 (EXOC8).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Exocyst complex component 8 (EXOC8).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Exocyst complex component 8 (EXOC8).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Exocyst complex component 8 (EXOC8).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Exocyst complex component 8 (EXOC8).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Exocyst complex component 8 (EXOC8).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Exocyst complex component 8 (EXOC8).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Exocyst complex component 8 (EXOC8).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Exocyst complex component 8 (EXOC8).	[9]

References

• [1] High-throughput discovery of novel developmental phenotypes. Nature. 2016 Sep 22;537(7621):508-514. doi: 10.1038/nature19356. Epub 2016 Sep 14.
• [2] 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.
• [3] 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.
• [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] 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] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.