Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQJ05ZS)

DOT Name Sentrin-specific protease 7 (SENP7)
Synonyms EC 3.4.22.-; SUMO-1-specific protease 2; Sentrin/SUMO-specific protease SENP7
Gene Name SENP7
Related Disease
Autism ( )
Autism spectrum disorder ( )
Herpes simplex infection ( )
Inflammatory bowel disease ( )
Prostate neoplasm ( )
Stargardt disease ( )
Breast cancer ( )
Breast carcinoma ( )
Hepatocellular carcinoma ( )
UniProt ID
SENP7_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3EAY; 7R2E
EC Number
3.4.22.-
Pfam ID
PF02902
Sequence
MDKRKLGRRPSSSEIITEGKRKKSSSDLSEIRKMLNAKPEDVHVQSPLSKFRSSERWTLP
LQWERSLRNKVISLDHKNKKHIRGCPVTSKSSPERQLKVMLTNVLWTDLGRKFRKTLPRN
DANLCDANKVQSDSLPSTSVDSLETCQKLEPLRQSLNLSERIPRVILTNVLGTELGRKYI
RTPPVTEGSLSDTDNLQSEQLSSSSDGSLESYQNLNPHKSCYLSERGSQRSKTVDDNSAK
QTAHNKEKRRKDDGISLLISDTQPEDLNSGSRGCDHLEQESRNKDVKYSDSKVELTLISR
KTKRRLRNNLPDSQYCTSLDKSTEQTKKQEDDSTISTEFEKPSENYHQDPKLPEEITTKP
TKSDFTKLSSLNSQELTLSNATKSASAGSTTETVENSNSIDIVGISSLVEKDENELNTIE
KPILRGHNEGNQSLISAEPIVVSSDEEGPVEHKSSEILKLQSKQDRETTNENESTSESAL
LELPLITCESVQMSSELCPYNPVMENISSIMPSNEMDLQLDFIFTSVYIGKIKGASKGCV
TITKKYIKIPFQVSLNEISLLVDTTHLKRFGLWKSKDDNHSKRSHAILFFWVSSDYLQEI
QTQLEHSVLSQQSKSSEFIFLELHNPVSQREELKLKDIMTEISIISGELELSYPLSWVQA
FPLFQNLSSKESSFIHYYCVSTCSFPAGVAVAEEMKLKSVSQPSNTDAAKPTYTFLQKQS
SGCYSLSITSNPDEEWREVRHTGLVQKLIVYPPPPTKGGLGVTNEDLECLEEGEFLNDVI
IDFYLKYLILEKASDELVERSHIFSSFFYKCLTRKENNLTEDNPNLSMAQRRHKRVRTWT
RHINIFNKDYIFVPVNESSHWYLAVICFPWLEEAVYEDFPQTVSQQSQAQQSQNDNKTID
NDLRTTSTLSLSAEDSQSTESNMSVPKKMCKRPCILILDSLKAASVQNTVQNLREYLEVE
WEVKLKTHRQFSKTNMVDLCPKVPKQDNSSDCGVYLLQYVESFFKDPIVNFELPIHLEKW
FPRHVIKTKREDIRELILKLHLQQQKGSSS
Function
Protease that acts as a positive regulator of the cGAS-STING pathway by catalyzing desumoylation of CGAS. Desumoylation of CGAS promotes DNA-binding activity of CGAS, subsequent oligomerization and activation. Deconjugates SUMO2 and SUMO3 from targeted proteins, but not SUMO1. Catalyzes the deconjugation of poly-SUMO2 and poly-SUMO3 chains. Has very low efficiency in processing full-length SUMO proteins to their mature forms.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autism DISV4V1Z Strong Biomarker [1]
Autism spectrum disorder DISXK8NV Strong Genetic Variation [2]
Herpes simplex infection DISL1SAV Strong Biomarker [3]
Inflammatory bowel disease DISGN23E Strong Biomarker [4]
Prostate neoplasm DISHDKGQ Strong Altered Expression [5]
Stargardt disease DISPXOTO Strong Genetic Variation [6]
Breast cancer DIS7DPX1 Limited Genetic Variation [7]
Breast carcinoma DIS2UE88 Limited Genetic Variation [7]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [8]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Sentrin-specific protease 7 (SENP7). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Sentrin-specific protease 7 (SENP7). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Sentrin-specific protease 7 (SENP7). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Sentrin-specific protease 7 (SENP7). [12]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Sentrin-specific protease 7 (SENP7). [13]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Sentrin-specific protease 7 (SENP7). [14]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Sentrin-specific protease 7 (SENP7). [15]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of Sentrin-specific protease 7 (SENP7). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Sentrin-specific protease 7 (SENP7). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Sentrin-specific protease 7 (SENP7). [18]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Sentrin-specific protease 7 (SENP7). [19]
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⏷ Show the Full List of 11 Drug(s)

References

1 Exploring the Sensory Profiles of Children on the Autism Spectrum Using the Short Sensory Profile-2 (SSP-2).J Autism Dev Disord. 2019 May;49(5):2069-2079. doi: 10.1007/s10803-019-03889-2.
2 Adaptation and psychometric properties of the Polish version of the Short Sensory Profile 2.Medicine (Baltimore). 2019 Nov;98(44):e17689. doi: 10.1097/MD.0000000000017689.
3 SENP7 Potentiates cGAS Activation by Relieving SUMO-Mediated Inhibition of Cytosolic DNA Sensing.PLoS Pathog. 2017 Jan 17;13(1):e1006156. doi: 10.1371/journal.ppat.1006156. eCollection 2017 Jan.
4 DeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells.Cell Rep. 2019 Dec 10;29(11):3522-3538.e7. doi: 10.1016/j.celrep.2019.11.028.
5 SPOP E3 Ubiquitin Ligase Adaptor Promotes Cellular Senescence by Degrading the SENP7 deSUMOylase.Cell Rep. 2015 Nov 10;13(6):1183-1193. doi: 10.1016/j.celrep.2015.09.083. Epub 2015 Oct 29.
6 Color vision in Stargardt's disease.Int Ophthalmol. 1992 Nov;16(6):423-8. doi: 10.1007/BF00918432.
7 Association of SENPs single-nucleotide polymorphism and breast cancer in Chinese population.Medicine (Baltimore). 2019 Feb;98(6):e14168. doi: 10.1097/MD.0000000000014168.
8 Speckle-type POZ protein suppresses hepatocellular carcinoma cell migration and invasion via ubiquitin-dependent proteolysis of SUMO1/sentrin specific peptidase 7.Biochem Biophys Res Commun. 2018 Jul 7;502(1):30-42. doi: 10.1016/j.bbrc.2018.05.115. Epub 2018 May 24.
9 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 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.
12 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
13 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
14 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
15 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
16 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.
17 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
18 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.
19 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.