Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY1X6A2)

• DOT Name: Protein transport protein Sec61 subunit beta (SEC61B)
• Gene Name: SEC61B
• Related Disease:
  Polycystic liver disease 1
  Autosomal dominant polycystic liver disease
  Neuroblastoma
  SEC61B-related polycystic liver disease
• UniProt ID: SC61B_HUMAN
• PDB ID: 6W6L; 8B6L; 8DNV; 8DNW; 8DNX; 8DNY; 8DNZ; 8DO0; 8DO1; 8DO2; 8DO3
• Pfam ID: PF03911
• Sequence:
  MPGPTPSGTNVGSSGRSPSKAVAARAAGSTVRQRKNASCGTRSAGRTTSAGTGGMWRFYT
  EDSPGLKVGPVPVLVMSLLFIASVFMLHIWGKYTRS
• 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
Polycystic liver disease 1	DIS52T2A	Moderate	Autosomal dominant	[1]
Autosomal dominant polycystic liver disease	DISJS005	Disputed	Genetic Variation	[2]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[3]
SEC61B-related polycystic liver disease	DISQV9UC	Limited	Autosomal dominant	[4]

2 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 Protein transport protein Sec61 subunit beta (SEC61B).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein transport protein Sec61 subunit beta (SEC61B).	[14]

14 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 beta (SEC61B).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[10]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[10]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein transport protein Sec61 subunit beta (SEC61B).	[18]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Genetics of polycystic liver diseases.Curr Opin Gastroenterol. 2019 Mar;35(2):65-72. doi: 10.1097/MOG.0000000000000514.
• [3] 3,4-dihydroxybenzalacetone and caffeic acid phenethyl ester induce preconditioning ER stress and autophagy in SH-SY5Y cells.J Cell Physiol. 2018 Feb;233(2):1671-1684. doi: 10.1002/jcp.26080. Epub 2017 Aug 23.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [16] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.