Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7MJRXY)

• DOT Name: Protein transport protein Sec61 subunit gamma (SEC61G)
• Gene Name: SEC61G
• Related Disease:
  Non-small-cell lung cancer
  Systemic lupus erythematosus
  Adult glioblastoma
  Glioblastoma multiforme
• UniProt ID: SC61G_HUMAN
• PDB ID: 6W6L; 8B6L; 8DNV; 8DNW; 8DNX; 8DNY; 8DNZ; 8DO0; 8DO1; 8DO2; 8DO3
• Pfam ID: PF00584
• Sequence:
  MDQVMQFVEPSRQFVKDSIRLVKRCTKPDRKEFQKIAMATAIGFAIMGFIGFFVKLIHIP
  INNIIVGG
• Function: Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides. The SEC61 channel is also involved in ER membrane insertion of transmembrane proteins: it mediates membrane insertion of the first few transmembrane segments of proteins, while insertion of subsequent transmembrane regions of multi-pass membrane proteins is mediated by the multi-pass translocon (MPT) complex. The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER.
• KEGG Pathway:
  Protein export (hsa03060)
  Protein processing in endoplasmic reticulum (hsa04141)
  Phagosome (hsa04145)
  Vibrio cholerae infection (hsa05110)
• Reactome Pathway:
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  Insertion of tail-anchored proteins into the endoplasmic reticulum membrane (R-HSA-9609523)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Disputed	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[3]

12 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 Protein transport protein Sec61 subunit gamma (SEC61G).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[9]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[10]
Sertraline	DM0FB1J	Approved	Sertraline decreases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein transport protein Sec61 subunit gamma (SEC61G).	[15]

References

• [1] LncRNA LINC02418 regulates proliferation and apoptosis of non-small cell lung cancer cells by regulating miR-4677-3p/SEC61G.Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10354-10362. doi: 10.26355/eurrev_201912_19673.
• [2] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [3] Identification of SEC61G as a Novel Prognostic Marker for Predicting Survival and Response to Therapies in Patients with Glioblastoma.Med Sci Monit. 2019 May 16;25:3624-3635. doi: 10.12659/MSM.916648.
• [4] 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.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] 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.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [11] Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.