Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ICPMK)

DOT Name Translocation protein SEC63 homolog (SEC63)
Gene Name SEC63
Related Disease
Polycystic liver disease 2 ( )
Hereditary nonpolyposis colon cancer ( )
Lynch syndrome ( )
Autosomal dominant polycystic kidney disease ( )
Autosomal dominant polycystic liver disease ( )
Polycystic liver disease 1 ( )
Polycystic kidney disease ( )
UniProt ID
SEC63_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00226 ; PF02889
Sequence
MAGQQFQYDDSGNTFFYFLTSFVGLIVIPATYYLWPRDQNAEQIRLKNIRKVYGRCMWYR
LRLLKPQPNIIPTVKKIVLLAGWALFLFLAYKVSKTDREYQEYNPYEVLNLDPGATVAEI
KKQYRLLSLKYHPDKGGDEVMFMRIAKAYAALTDEESRKNWEEFGNPDGPQATSFGIALP
AWIVDQKNSILVLLVYGLAFMVILPVVVGSWWYRSIRYSGDQILIRTTQIYTYFVYKTRN
MDMKRLIMVLAGASEFDPQYNKDATSRPTDNILIPQLIREIGSINLKKNEPPLTCPYSLK
ARVLLLSHLARMKIPETLEEDQQFMLKKCPALLQEMVNVICQLIVMARNREEREFRAPTL
ASLENCMKLSQMAVQGLQQFKSPLLQLPHIEEDNLRRVSNHKKYKIKTIQDLVSLKESDR
HTLLHFLEDEKYEEVMAVLGSFPYVTMDIKSQVLDDEDSNNITVGSLVTVLVKLTRQTMA
EVFEKEQSICAAEEQPAEDGQGETNKNRTKGGWQQKSKGPKKTAKSKKKKPLKKKPTPVL
LPQSKQQKQKQANGVVGNEAAVKEDEEEVSDKGSDSEEEETNRDSQSEKDDGSDRDSDRE
QDEKQNKDDEAEWQELQQSIQRKERALLETKSKITHPVYSLYFPEEKQEWWWLYIADRKE
QTLISMPYHVCTLKDTEEVELKFPAPGKPGNYQYTVFLRSDSYMGLDQIKPLKLEVHEAK
PVPENHPQWDTAIEGDEDQEDSEGFEDSFEEEEEEEEDDD
Function
Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER). Proposed to play an auxiliary role in recognition of precursors with short and apolar signal peptides. May cooperate with SEC62 and HSPA5/BiP to facilitate targeting of small presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen. Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia.
Tissue Specificity Widely expressed, with high levels in the liver.
KEGG Pathway
Protein export (hsa03060 )
Protein processing in endoplasmic reticulum (hsa04141 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Polycystic liver disease 2 DISF25HM Definitive Autosomal dominant [1]
Hereditary nonpolyposis colon cancer DISPA49R Strong Biomarker [2]
Lynch syndrome DIS3IW5F Strong Biomarker [2]
Autosomal dominant polycystic kidney disease DISBHWUI moderate Biomarker [3]
Autosomal dominant polycystic liver disease DISJS005 moderate Biomarker [4]
Polycystic liver disease 1 DIS52T2A Supportive Autosomal dominant [5]
Polycystic kidney disease DISWS3UY Limited Biomarker [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Translocation protein SEC63 homolog (SEC63). [7]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Translocation protein SEC63 homolog (SEC63). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Translocation protein SEC63 homolog (SEC63). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Translocation protein SEC63 homolog (SEC63). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Translocation protein SEC63 homolog (SEC63). [11]
Menadione DMSJDTY Approved Menadione affects the expression of Translocation protein SEC63 homolog (SEC63). [12]
Clozapine DMFC71L Approved Clozapine increases the expression of Translocation protein SEC63 homolog (SEC63). [13]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Translocation protein SEC63 homolog (SEC63). [14]
Benzatropine DMF7EXL Approved Benzatropine increases the expression of Translocation protein SEC63 homolog (SEC63). [13]
Haloperidol DM96SE0 Approved Haloperidol increases the expression of Translocation protein SEC63 homolog (SEC63). [13]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Translocation protein SEC63 homolog (SEC63). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Translocation protein SEC63 homolog (SEC63). [16]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Translocation protein SEC63 homolog (SEC63). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Translocation protein SEC63 homolog (SEC63). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Translocation protein SEC63 homolog (SEC63). [20]
Okadaic acid DM47CO1 Investigative Okadaic acid decreases the expression of Translocation protein SEC63 homolog (SEC63). [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Translocation protein SEC63 homolog (SEC63). [17]
------------------------------------------------------------------------------------

References

1 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.
2 Hepatocellular carcinoma as extracolonic manifestation of Lynch syndrome indicates SEC63 as potential target gene in hepatocarcinogenesis.Scand J Gastroenterol. 2013 Mar;48(3):344-51. doi: 10.3109/00365521.2012.752030.
3 Endoplasmic reticulum stress and monogenic kidney diseases in precision nephrology.Pediatr Nephrol. 2019 Sep;34(9):1493-1500. doi: 10.1007/s00467-018-4031-2. Epub 2018 Aug 11.
4 Severe Polycystic Liver Disease Is Not Caused by Large Deletions of the PRKCSH Gene.J Clin Lab Anal. 2016 Sep;30(5):431-6. doi: 10.1002/jcla.21875. Epub 2015 Sep 13.
5 Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management. Orphanet J Rare Dis. 2014 May 1;9:69. doi: 10.1186/1750-1172-9-69.
6 Genetics of polycystic liver diseases.Curr Opin Gastroenterol. 2019 Mar;35(2):65-72. doi: 10.1097/MOG.0000000000000514.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 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.
13 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.
14 Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
15 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
16 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.
17 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.
18 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
19 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
20 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
21 Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.