Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4YA137)

• DOT Name: Exocyst complex component 7 (EXOC7)
• Synonyms: Exocyst complex component Exo70
• Gene Name: EXOC7
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Dengue
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Neurodevelopmental disorder with seizures and brain atrophy
  Varicose veins
  Complex neurodevelopmental disorder
• UniProt ID: EXOC7_HUMAN
• Pfam ID: PF03081 ; PF20669
• Sequence:
  MIPPQEASARRREIEDKLKQEEETLSFIRDSLEKSDQLTKNMVSILSSFESRLMKLENSI
  IPVHKQTENLQRLQENVEKTLSCLDHVISYYHVASDTEKIIREGPTGRLEEYLGSMAKIQ
  KAVEYFQDNSPDSPELNKVKLLFERGKEALESEFRSLMTRHSKVVSPVLILDLISGDDDL
  EAQEDVTLEHLPESVLQDVIRISRWLVEYGRNQDFMNVYYQIRSSQLDRSIKGLKEHFHK
  SSSSSGVPYSPAIPNKRKDTPTKKPVKRPGTIRKAQNLLKQYSQHGLDGKKGGSNLIPLE
  GLLPCTPRGGLPGPWINAACVCAADISPGHEHDFRVKHLSEALNDKHGPLAGRDDMLDVE
  TDAYIHCVSAFVKLAQSEYQLLADIIPEHHQKKTFDSLIQDALDGLMLEGENIVSAARKA
  IVRHDFSTVLTVFPILRHLKQTKPEFDQVLQGTAASTKNKLPGLITSMETIGAKALEDFA
  DNIKNDPDKEYNMPKDGTVHELTSNAILFLQQLLDFQETAGAMLASQETSSSATSYSSEF
  SKRLLSTYICKVLGNLQLNLLSKSKVYEDPALSAIFLHNNYNYILKSLEKSELIQLVAVT
  QKTAERSYREHIEQQIQTYQRSWLKVTDYIAEKNLPVFQPGVKLRDKERQIIKERFKGFN
  DGLEELCKIQKAWAIPDTEQRDRIRQAQKTIVKETYGAFLQKFGSVPFTKNPEKYIKYGV
  EQVGDMIDRLFDTSA
• Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. In adipocytes, plays a crucial role in targeting SLC2A4 vesicle to the plasma membrane in response to insulin, perhaps directing the vesicle to the precise site of fusion. It is required for neuron survival and plays an essential role in cortical development.
• Tissue Specificity: Abundant in the ventricular zone, the outer subventricular zone and the cortical plate of the fetal cortex.
• KEGG Pathway:
  Insulin sig.ling pathway (hsa04910)
  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

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Dengue	DISKH221	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Neurodevelopmental disorder with seizures and brain atrophy	DISAL3A7	Strong	Autosomal recessive	[5]
Varicose veins	DISIMBN2	Strong	Biomarker	[6]
Complex neurodevelopmental disorder	DISB9AFI	Moderate	Autosomal recessive	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Exocyst complex component 7 (EXOC7) affects the response to substance of Methotrexate.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Exocyst complex component 7 (EXOC7).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Exocyst complex component 7 (EXOC7).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Exocyst complex component 7 (EXOC7).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Exocyst complex component 7 (EXOC7).	[11]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Exocyst complex component 7 (EXOC7).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Exocyst complex component 7 (EXOC7).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Exocyst complex component 7 (EXOC7).	[15]

2 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 7 (EXOC7).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Exocyst complex component 7 (EXOC7).	[14]

References

• [1] Exo70 isoform switching upon epithelial-mesenchymal transition mediates cancer cell invasion.Dev Cell. 2013 Dec 9;27(5):560-73. doi: 10.1016/j.devcel.2013.10.020.
• [2] Exo70 is an independent prognostic factor in colon cancer.Sci Rep. 2017 Jul 11;7(1):5039. doi: 10.1038/s41598-017-05308-x.
• [3] EXO70 protein influences dengue virus secretion.Microbes Infect. 2011 Feb;13(2):143-50. doi: 10.1016/j.micinf.2010.10.011. Epub 2010 Oct 27.
• [4] Exo70 is transcriptionally up-regulated by hepatic nuclear factor 4 and contributes to cell cycle control in hepatoma cells.Oncotarget. 2016 Feb 23;7(8):9150-62. doi: 10.18632/oncotarget.7133.
• [5] Regulation of human cerebral cortical development by EXOC7 and EXOC8, components of the exocyst complex, and roles in neural progenitor cell proliferation and survival. Genet Med. 2020 Jun;22(6):1040-1050. doi: 10.1038/s41436-020-0758-9. Epub 2020 Feb 27.
• [6] Drosophila Exo70 Is Essential for Neurite Extension and Survival under Thermal Stress.J Neurosci. 2018 Sep 12;38(37):8071-8086. doi: 10.1523/JNEUROSCI.0620-18.2018. Epub 2018 Aug 1.
• [7] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [11] 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.
• [12] 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.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.