Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX1CC39)

• DOT Name: Exocyst complex component 1 (EXOC1)
• Synonyms: Exocyst complex component Sec3
• Gene Name: EXOC1
• Related Disease:
  Cervical cancer
  Advanced cancer
  Cervical carcinoma
  Lung cancer
  Lung carcinoma
  Methicillin-resistant staphylococci infection
• UniProt ID: EXOC1_HUMAN
• Pfam ID: PF15277 ; PF20654 ; PF09763
• Sequence:
  MTAIKHALQRDIFTPNDERLLSIVNVCKAGKKKKNCFLCATVTTERPVQVKVVKVKKSDK
  GDFYKRQIAWALRDLAVVDAKDAIKENPEFDLHFEKIYKWVASSTAEKNAFISCIWKLNQ
  RYLRKKIDFVNVSSQLLEESVPSGENQSVTGGDEEVVDEYQELNAREEQDIEIMMEGCEY
  AISNAEAFAEKLSRELQVLDGANIQSIMASEKQVNILMKLLDEALKEVDQIELKLSSYEE
  MLQSVKEQMDQISESNHLIHLSNTNNVKLLSEIEFLVNHMDLAKGHIKALQEGDLASSRG
  IEACTNAADALLQCMNVALRPGHDLLLAVKQQQQRFSDLRELFARRLASHLNNVFVQQGH
  DQSSTLAQHSVELTLPNHHPFHRDLLRYAKLMEWLKSTDYGKYEGLTKNYMDYLSRLYER
  EIKDFFEVAKIKMTGTTKESKKFATLPRKESAVKQETESLHGSSGKLTGSTSSLNKLSVQ
  SSGNRRSQSSSLLDMGNMSASDLDVADRTKFDKIFEQVLSELEPLCLAEQDFISKFFKLQ
  QHQSMPGTMAEAEDLDGGTLSRQHNCGTPLPVSSEKDMIRQMMIKIFRCIEPELNNLIAL
  GDKIDSFNSLYMLVKMSHHVWTAQNVDPASFLSTTLGNVLVTVKRNFDKCISNQIRQMEE
  VKISKKSKVGILPFVAEFEEFAGLAESIFKNAERRGDLDKAYTKLIRGVFVNVEKVANES
  QKTPRDVVMMENFHHIFATLSRLKISCLEAEKKEAKQKYTDHLQSYVIYSLGQPLEKLNH
  FFEGVEARVAQGIREEEVSYQLAFNKQELRKVIKEYPGKEVKKGLDNLYKKVDKHLCEEE
  NLLQVVWHSMQDEFIRQYKHFEGLIARCYPGSGVTMEFTIQDILDYCSSIAQSH
• Function: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.; (Microbial infection) Has an antiviral effect against flaviviruses by affecting viral RNA transcription and translation through the sequestration of elongation factor 1-alpha (EEF1A1). This results in decreased viral RNA synthesis and decreased viral protein translation.
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[3]

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 1 (EXOC1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Exocyst complex component 1 (EXOC1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Exocyst complex component 1 (EXOC1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Exocyst complex component 1 (EXOC1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Exocyst complex component 1 (EXOC1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Exocyst complex component 1 (EXOC1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Exocyst complex component 1 (EXOC1).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Exocyst complex component 1 (EXOC1).	[12]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Exocyst complex component 1 (EXOC1).	[8]

References

• [1] Immuno-related polymorphisms and cervical cancer risk: The IARC multicentric case-control study.PLoS One. 2017 May 15;12(5):e0177775. doi: 10.1371/journal.pone.0177775. eCollection 2017.
• [2] Sec3 knockdown inhibits TGF- induced epithelial-mesenchymal transition through the down-regulation of Akt phosphorylation in A549 cells.Biochem Biophys Res Commun. 2019 Nov 5;519(2):253-260. doi: 10.1016/j.bbrc.2019.08.145. Epub 2019 Sep 5.
• [3] Molecular Characterization of Methicillin-Resistant Staphylococcus aureus from Outpatients in Northern Japan: Increasing Tendency of ST5/ST764 MRSA-IIa with Arginine Catabolic Mobile Element.Microb Drug Resist. 2017 Jul;23(5):616-625. doi: 10.1089/mdr.2016.0176. Epub 2016 Nov 21.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [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] 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.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.