Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5EWXAN)

DOT Name Exocyst complex component 4 (EXOC4)
Synonyms Exocyst complex component Sec8
Gene Name EXOC4
Related Disease
Autosomal dominant polycystic kidney disease ( )
Alzheimer disease ( )
Food allergy ( )
Malignant peripheral nerve sheath tumor ( )
Schizophrenia ( )
Neoplasm ( )
Obesity ( )
Squamous cell carcinoma ( )
Non-insulin dependent diabetes ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rheumatoid arthritis ( )
UniProt ID
EXOC4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7PC5
Pfam ID
PF20652 ; PF04048
Sequence
MAAEAAGGKYRSTVSKSKDPSGLLISVIRTLSTSDDVEDRENEKGRLEEAYEKCDRDLDE
LIVQHYTELTTAIRTYQSITERITNSRNKIKQVKENLLSCKMLLHCKRDELRKLWIEGIE
HKHVLNLLDEIENIKQVPQKLEQCMASKHYLSATDMLVSAVESLEGPLLQVEGLSDLRLE
LHSKKMNLHLVLIDELHRHLYIKSTSRVVQRNKEKGKISSLVKDASVPLIDVTNLPTPRK
FLDTSHYSTAGSSSVREINLQDIKEDLELDPEENSTLFMGILIKGLAKLKKIPETVKAII
ERLEQELKQIVKRSTTQVADSGYQRGENVTVENQPRLLLELLELLFDKFNAVAAAHSVVL
GYLQDTVVTPLTQQEDIKLYDMADVWVKIQDVLQMLLTEYLDMKNTRTASEPSAQLSYAS
TGREFAAFFAKKKPQRPKNSLFKFESSSHAISMSAYLREQRRELYSRSGELQGGPDDNLI
EGGGTKFVCKPGARNITVIFHPLLRFIQEIEHALGLGPAKQCPLREFLTVYIKNIFLNQV
LAEINKEIEGVTKTSDPLKILANADTMKVLGVQRPLLQSTIIVEKTVQDLLNLMHDLSAY
SDQFLNMVCVKLQEYKDTCTAAYRGIVQSEEKLVISASWAKDDDISRLLKSLPNWMNMAQ
PKQLRPKREEEEDFIRAAFGKESEVLIGNLGDKLIPPQDILRDVSDLKALANMHESLEWL
ASRTKSAFSNLSTSQMLSPAQDSHTNTDLPPVSEQIMQTLSELAKSFQDMADRCLLVLHL
EVRVHCFHYLIPLAKEGNYAIVANVESMDYDPLVVKLNKDISAIEEAMSASLQQHKFQYI
FEGLGHLISCILINGAQYFRRISESGIKKMCRNIFVLQQNLTNITMSREADLDFARQYYE
MLYNTADELLNLVVDQGVKYTELEYIHALTLLHRSQTGVGELTTQNTRLQRLKEIICEQA
AIKQATKDKKITTV
Function Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
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

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal dominant polycystic kidney disease DISBHWUI Definitive Biomarker [1]
Alzheimer disease DISF8S70 Strong Genetic Variation [2]
Food allergy DISMQ1BP Strong Genetic Variation [3]
Malignant peripheral nerve sheath tumor DIS0JTN6 Strong Biomarker [4]
Schizophrenia DISSRV2N Strong Genetic Variation [5]
Neoplasm DISZKGEW moderate Altered Expression [6]
Obesity DIS47Y1K moderate Biomarker [7]
Squamous cell carcinoma DISQVIFL moderate Biomarker [6]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [8]
Prostate cancer DISF190Y Limited Genetic Variation [9]
Prostate carcinoma DISMJPLE Limited Genetic Variation [9]
Rheumatoid arthritis DISTSB4J Limited Biomarker [10]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 Exocyst complex component 4 (EXOC4). [11]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Exocyst complex component 4 (EXOC4). [12]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Exocyst complex component 4 (EXOC4). [13]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Exocyst complex component 4 (EXOC4). [14]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Exocyst complex component 4 (EXOC4). [16]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Exocyst complex component 4 (EXOC4). [17]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Exocyst complex component 4 (EXOC4). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Exocyst complex component 4 (EXOC4). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Exocyst complex component 4 (EXOC4). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Exocyst complex component 4 (EXOC4). [22]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Exocyst complex component 4 (EXOC4). [23]
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⏷ Show the Full List of 11 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Exocyst complex component 4 (EXOC4). [15]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Exocyst complex component 4 (EXOC4). [20]
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References

1 Compromised cytoarchitecture and polarized trafficking in autosomal dominant polycystic kidney disease cells.J Cell Biol. 2000 Apr 3;149(1):111-24. doi: 10.1083/jcb.149.1.111.
2 Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
3 Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy.J Allergy Clin Immunol. 2018 Mar;141(3):991-1001. doi: 10.1016/j.jaci.2017.09.015. Epub 2017 Oct 10.
4 Sec6/8 regulates Bcl-2 and Mcl-1, but not Bcl-xl, in malignant peripheral nerve sheath tumor cells.Apoptosis. 2016 May;21(5):594-608. doi: 10.1007/s10495-016-1230-9.
5 Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
6 Exocyst complex component Sec8: a presumed component in the progression of human oral squamous-cell carcinoma by secretion of matrix metalloproteinases.J Cancer Res Clin Oncol. 2013 Apr;139(4):533-42. doi: 10.1007/s00432-012-1356-2. Epub 2012 Dec 4.
7 Genome-Wide Interaction and Pathway Association Studies for Body Mass Index.Front Genet. 2019 May 1;10:404. doi: 10.3389/fgene.2019.00404. eCollection 2019.
8 Polymorphisms near EXOC4 and LRGUK on chromosome 7q32 are associated with Type 2 Diabetes and fasting glucose; the NHLBI Family Heart Study.BMC Med Genet. 2008 May 22;9:46. doi: 10.1186/1471-2350-9-46.
9 Genetic variations in TP53 binding sites are predictors of clinical outcomes in prostate cancer patients.Arch Toxicol. 2014 Apr;88(4):901-11. doi: 10.1007/s00204-014-1196-8. Epub 2014 Jan 22.
10 Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population.Arthritis Rheum. 2005 May;52(5):1371-80. doi: 10.1002/art.21013.
11 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.
12 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
13 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
14 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.
15 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
16 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.
17 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
18 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
19 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
20 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.
21 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
22 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.
23 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.