Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5QG1WG)

• DOT Name: Exocyst complex component 2 (EXOC2)
• Synonyms: Exocyst complex component Sec5
• Gene Name: EXOC2
• Related Disease:
  Advanced cancer
  B-cell lymphoma
  Glaucoma/ocular hypertension
  Open-angle glaucoma
  Pancreatic cancer
  Spondylocarpotarsal synostosis syndrome
  Alopecia
  Complex neurodevelopmental disorder
  Lymphoplasmacytic lymphoma
  Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia
  Psoriasis
  Waldenstrom macroglobulinemia
• UniProt ID: EXOC2_HUMAN
• Pfam ID: PF15469 ; PF01833
• Sequence:
  MSRSRQPPLVTGISPNEGIPWTKVTIRGENLGTGPTDLIGLTICGHNCLLTAEWMSASKI
  VCRVGQAKNDKGDIIVTTKSGGRGTSTVSFKLLKPEKIGILDQSAVWVDEMNYYDMRTDR
  NKGIPPLSLRPANPLGIEIEKSKFSQKDLEMLFHGMSADFTSENFSAAWYLIENHSNTSF
  EQLKMAVTNLKRQANKKSEGSLAYVKGGLSTFFEAQDALSAIHQKLEADGTEKVEGSMTQ
  KLENVLNRASNTADTLFQEVLGRKDKADSTRNALNVLQRFKFLFNLPLNIERNIQKGDYD
  VVINDYEKAKSLFGKTEVQVFKKYYAEVETRIEALRELLLDKLLETPSTLHDQKRYIRYL
  SDLHASGDPAWQCIGAQHKWILQLMHSCKEGYVKDLKGNPGLHSPMLDLDNDTRPSVLGH
  LSQTASLKRGSSFQSGRDDTWRYKTPHRVAFVEKLTKLVLSQLPNFWKLWISYVNGSLFS
  ETAEKSGQIERSKNVRQRQNDFKKMIQEVMHSLVKLTRGALLPLSIRDGEAKQYGGWEVK
  CELSGQWLAHAIQTVRLTHESLTALEIPNDLLQTIQDLILDLRVRCVMATLQHTAEEIKR
  LAEKEDWIVDNEGLTSLPCQFEQCIVCSLQSLKGVLECKPGEASVFQQPKTQEEVCQLSI
  NIMQVFIYCLEQLSTKPDADIDTTHLSVDVSSPDLFGSIHEDFSLTSEQRLLIVLSNCCY
  LERHTFLNIAEHFEKHNFQGIEKITQVSMASLKELDQRLFENYIELKADPIVGSLEPGIY
  AGYFDWKDCLPPTGVRNYLKEALVNIIAVHAEVFTISKELVPRVLSKVIEAVSEELSRLM
  QCVSSFSKNGALQARLEICALRDTVAVYLTPESKSSFKQALEALPQLSSGADKKLLEELL
  NKFKSSMHLQLTCFQAASSTMMKT
• Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
• Tissue Specificity: Widely expressed with highest levels in brain and placenta.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  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
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[2]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Genetic Variation	[3]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[4]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[5]
Spondylocarpotarsal synostosis syndrome	DISF9VP3	Strong	Genetic Variation	[6]
Alopecia	DIS37HU4	Limited	Genetic Variation	[7]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[8]
Lymphoplasmacytic lymphoma	DISMSQ11	Limited	Genetic Variation	[9]
Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia	DIS6FWH7	Limited	Unknown	[10]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[11]
Waldenstrom macroglobulinemia	DIS9O23I	Limited	Genetic Variation	[9]

4 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 2 (EXOC2).	[12]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Exocyst complex component 2 (EXOC2).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Exocyst complex component 2 (EXOC2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Exocyst complex component 2 (EXOC2).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Exocyst complex component 2 (EXOC2).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Exocyst complex component 2 (EXOC2).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Exocyst complex component 2 (EXOC2).	[16]
Marinol	DM70IK5	Approved	Marinol affects the expression of Exocyst complex component 2 (EXOC2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Exocyst complex component 2 (EXOC2).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Exocyst complex component 2 (EXOC2).	[21]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Exocyst complex component 2 (EXOC2).	[22]

References

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• [2] Integrating understanding of epidemiology and genomics in B-cell non-Hodgkin lymphoma as a pathway to novel management strategies.Discov Med. 2016 Mar;21(115):181-8.
• [3] Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma.Nat Genet. 2018 Aug;50(8):1067-1071. doi: 10.1038/s41588-018-0176-y. Epub 2018 Jul 27.
• [4] A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nat Commun. 2018 Jun 11;9(1):2278. doi: 10.1038/s41467-018-04555-4.
• [5] Ras-related small GTPases RalA and RalB regulate cellular survival after ionizing radiation.Int J Radiat Oncol Biol Phys. 2010 Sep 1;78(1):205-12. doi: 10.1016/j.ijrobp.2010.03.023. Epub 2010 Jul 7.
• [6] Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.PLoS One. 2018 Jan 2;13(1):e0189498. doi: 10.1371/journal.pone.0189498. eCollection 2018.
• [7] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [8] 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.
• [9] Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrm macroglobulinemia.Nat Commun. 2018 Oct 10;9(1):4182. doi: 10.1038/s41467-018-06541-2.
• [10] Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma. Hum Mol Genet. 2011 Sep 15;20(18):3718-24. doi: 10.1093/hmg/ddr287. Epub 2011 Jun 23.
• [11] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [12] 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.
• [13] 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.
• [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] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [18] 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.
• [19] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [20] 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.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.