Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9S9NJ7)

• DOT Name: Exocyst complex component 5 (EXOC5)
• Synonyms: Exocyst complex component Sec10; hSec10
• Gene Name: EXOC5
• Related Disease:
  Autosomal dominant polycystic kidney disease
  Dysuria
  Episodic kinesigenic dyskinesia 1
  Neovascular age-related macular degeneration
• UniProt ID: EXOC5_HUMAN
• Pfam ID: PF07393 ; PF20667
• Sequence:
  MATTAELFEEPFVADEYIERLVWRTPGGGSRGGPEAFDPKRLLEEFVNHIQELQIMDERI
  QRKVEKLEQQCQKEAKEFAKKVQELQKSNQVAFQHFQELDEHISYVATKVCHLGDQLEGV
  NTPRQRAVEAQKLMKYFNEFLDGELKSDVFTNSEKIKEAADIIQKLHLIAQELPFDRFSE
  VKSKIASKYHDLECQLIQEFTSAQRRGEISRMREVAAVLLHFKGYSHCVDVYIKQCQEGA
  YLRNDIFEDAGILCQRVNKQVGDIFSNPETVLAKLIQNVFEIKLQSFVKEQLEECRKSDA
  EQYLKNLYDLYTRTTNLSSKLMEFNLGTDKQTFLSKLIKSIFISYLENYIEVETGYLKSR
  SAMILQRYYDSKNHQKRSIGTGGIQDLKERIRQRTNLPLGPSIDTHGETFLSQEVVVNLL
  QETKQAFERCHRLSDPSDLPRNAFRIFTILVEFLCIEHIDYALETGLAGIPSSDSRNANL
  YFLDVVQQANTIFHLFDKQFNDHLMPLISSSPKLSECLQKKKEIIEQMEMKLDTGIDRTL
  NCMIGQMKHILAAEQKKTDFKPEDENNVLIQYTNACVKVCAYVRKQVEKIKNSMDGKNVD
  TVLMELGVRFHRLIYEHLQQYSYSCMGGMLAICDVAEYRKCAKDFKIPMVLHLFDTLHAL
  CNLLVVAPDNLKQVCSGEQLANLDKNILHSFVQLRADYRSARLARHFS
• Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Salmonella infection (hsa05132)
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant polycystic kidney disease	DISBHWUI	Strong	Biomarker	[1]
Dysuria	DIS7ZXDJ	Strong	Altered Expression	[2]
Episodic kinesigenic dyskinesia 1	DISGVQMP	Strong	Biomarker	[1]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Exocyst complex component 5 (EXOC5).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Exocyst complex component 5 (EXOC5).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Exocyst complex component 5 (EXOC5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Exocyst complex component 5 (EXOC5).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Exocyst complex component 5 (EXOC5).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Exocyst complex component 5 (EXOC5).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Exocyst complex component 5 (EXOC5).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Exocyst complex component 5 (EXOC5).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Exocyst complex component 5 (EXOC5).	[12]

References

• [1] The exocyst protein Sec10 interacts with Polycystin-2 and knockdown causes PKD-phenotypes.PLoS Genet. 2011 Apr;7(4):e1001361. doi: 10.1371/journal.pgen.1001361. Epub 2011 Apr 7.
• [2] Urothelial Defects from Targeted Inactivation of Exocyst Sec10 in Mice Cause Ureteropelvic Junction Obstructions.PLoS One. 2015 Jun 5;10(6):e0129346. doi: 10.1371/journal.pone.0129346. eCollection 2015.
• [3] Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration.J Hum Genet. 2018 Oct;63(10):1083-1091. doi: 10.1038/s10038-018-0493-0. Epub 2018 Jul 27.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] 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.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.