Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT05LLF4)

DOT Name Sentrin-specific protease 6 (SENP6)
Synonyms EC 3.4.22.-; SUMO-1-specific protease 1; Sentrin/SUMO-specific protease SENP6
Gene Name SENP6
Related Disease
Advanced cancer ( )
Hepatocellular carcinoma ( )
Lyme disease ( )
Myopia ( )
Premature aging syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
UniProt ID
SENP6_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.4.22.-
Pfam ID
PF02902
Sequence
MAAGKSGGSAGEITFLEALARSESKRDGGFKNNWSFDHEEESEGDTDKDGTNLLSVDEDE
DSETSKGKKLNRRSEIVANSSGEFILKTYVRRNKSESFKTLKGNPIGLNMLSNNKKLSEN
TQNTSLCSGTVVHGRRFHHAHAQIPVVKTAAQSSLDRKERKEYPPHVQKVEINPVRLSRL
QGVERIMKKTEESESQVEPEIKRKVQQKRHCSTYQPTPPLSPASKKCLTHLEDLQRNCRQ
AITLNESTGPLLRTSIHQNSGGQKSQNTGLTTKKFYGNNVEKVPIDIIVNCDDSKHTYLQ
TNGKVILPGAKIPKITNLKERKTSLSDLNDPIILSSDDDDDNDRTNRRESISPQPADSAC
SSPAPSTGKVEAALNENTCRAERELRSIPEDSELNTVTLPRKARMKDQFGNSIINTPLKR
RKVFSQEPPDALALSCQSSFDSVILNCRSIRVGTLFRLLIEPVIFCLDFIKIQLDEPDHD
PVEIILNTSDLTKCEWCNVRKLPVVFLQAIPAVYQKLSIQLQMNKEDKVWNDCKGVNKLT
NLEEQYIILIFQNGLDPPANMVFESIINEIGIKNNISNFFAKIPFEEANGRLVACTRTYE
ESIKGSCGQKENKIKTVSFESKIQLRSKQEFQFFDEEEETGENHTIFIGPVEKLIVYPPP
PAKGGISVTNEDLHCLNEGEFLNDVIIDFYLKYLVLEKLKKEDADRIHIFSSFFYKRLNQ
RERRNHETTNLSIQQKRHGRVKTWTRHVDIFEKDFIFVPLNEAAHWFLAVVCFPGLEKPK
YEPNPHYHENAVIQKCSTVEDSCISSSASEMESCSQNSSAKPVIKKMLNKKHCIAVIDSN
PGQEESDPRYKRNICSVKYSVKKINHTASENEEFNKGESTSQKVADRTKSENGLQNESLS
STHHTDGLSKIRLNYSDESPEAGKMLEDELVDFSEDQDNQDDSSDDGFLADDNCSSEIGQ
WHLKPTICKQPCILLMDSLRGPSRSNVVKILREYLEVEWEVKKGSKRSFSKDVMKGSNPK
VPQQNNFSDCGVYVLQYVESFFENPILSFELPMNLANWFPPPRMRTKREEIRNIILKLQE
DQSKEKRKHKDTYSTEAPLGEGTEQYVNSISD
Function
Protease that deconjugates SUMO1, SUMO2 and SUMO3 from targeted proteins. Processes preferentially poly-SUMO2 and poly-SUMO3 chains, but does not efficiently process SUMO1, SUMO2 and SUMO3 precursors. Deconjugates SUMO1 from RXRA, leading to transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complex. Desumoylates PML and CENPI, protecting them from degradation by the ubiquitin ligase RNF4, which targets polysumoylated proteins for proteasomal degradation. Desumoylates also RPA1, thus preventing recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination.
Tissue Specificity Highly expressed in reproductive organs, such as testis, ovary and prostate.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Hepatocellular carcinoma DIS0J828 Strong Posttranslational Modification [2]
Lyme disease DISO70G5 Strong Biomarker [3]
Myopia DISK5S60 Strong Genetic Variation [4]
Premature aging syndrome DIS51AGT Strong Genetic Variation [5]
Prostate cancer DISF190Y Strong Biomarker [6]
Prostate carcinoma DISMJPLE Strong Biomarker [7]
Prostate neoplasm DISHDKGQ Strong Biomarker [6]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Sentrin-specific protease 6 (SENP6). [8]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Sentrin-specific protease 6 (SENP6). [17]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Sentrin-specific protease 6 (SENP6). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Sentrin-specific protease 6 (SENP6). [20]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Sentrin-specific protease 6 (SENP6). [19]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Sentrin-specific protease 6 (SENP6). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Sentrin-specific protease 6 (SENP6). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Sentrin-specific protease 6 (SENP6). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Sentrin-specific protease 6 (SENP6). [12]
Panobinostat DM58WKG Approved Panobinostat affects the expression of Sentrin-specific protease 6 (SENP6). [13]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Sentrin-specific protease 6 (SENP6). [14]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of Sentrin-specific protease 6 (SENP6). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Sentrin-specific protease 6 (SENP6). [16]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 affects the expression of Sentrin-specific protease 6 (SENP6). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Sentrin-specific protease 6 (SENP6). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Sentrin-specific protease 6 (SENP6). [21]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Sentrin-specific protease 6 (SENP6). [22]
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⏷ Show the Full List of 12 Drug(s)

References

1 Claudin 1 expression in basal-like breast cancer is related to patient age.BMC Cancer. 2013 May 30;13:268. doi: 10.1186/1471-2407-13-268.
2 Inhibition of SENP6-induced radiosensitization of human hepatocellular carcinoma cells by blocking radiation-induced NF-B activation.Cancer Biother Radiopharm. 2013 Apr;28(3):196-200. doi: 10.1089/cbr.2012.1288. Epub 2013 Mar 5.
3 Lyme Disease Risks in Europe under Multiple Uncertain Drivers of Change.Environ Health Perspect. 2019 Jun;127(6):67010. doi: 10.1289/EHP4615. Epub 2019 Jun 24.
4 Down scaling of climate change scenarii to river basin level: A transdisciplinary methodology applied to Evrotas river basin, Greece.Sci Total Environ. 2019 Apr 10;660:1623-1632. doi: 10.1016/j.scitotenv.2018.12.369. Epub 2018 Dec 26.
5 Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway.Nat Commun. 2018 Jan 10;9(1):143. doi: 10.1038/s41467-017-02413-3.
6 Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.Nat Genet. 2018 May;50(5):682-692. doi: 10.1038/s41588-018-0086-z. Epub 2018 Apr 16.
7 Silk scaffolds connected with different naturally occurring biomaterials for prostate cancer cell cultivation in 3D.Biopolymers. 2017 Feb;107(2):70-79. doi: 10.1002/bip.22993.
8 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.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
13 The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects. Clin Cancer Res. 2016 May 15;22(10):2534-44. doi: 10.1158/1078-0432.CCR-15-1666. Epub 2016 Jan 5.
14 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
15 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
16 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
17 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.
18 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.
19 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.
20 Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
21 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
22 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.