Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6CGYHW)

DOT Name Regulator of G-protein signaling 20 (RGS20)
Synonyms RGS20; Gz-selective GTPase-activating protein; G(z)GAP; Gz-GAP; Regulator of G-protein signaling Z1; Regulator of Gz-selective protein signaling 1
Gene Name RGS20
Related Disease
Breast cancer ( )
Breast carcinoma ( )
High blood pressure ( )
Neoplasm ( )
Triple negative breast cancer ( )
Bladder cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Substance dependence ( )
UniProt ID
RGS20_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00615
Sequence
MPQLSQDNQECLQKHFSRPSIWTQFLPLFRAQRYNTDIHQITENEGDLRAVPDIKSFPPA
QLPDSPAAPKLFGLLSSPLSSLARFFSHLLRRPPPEAPRRRLDFSPLLPALPAARLSRGH
EELPGRLSLLLGAALALPGRPSGGRPLRPPHPVAKPREEDATAGQSSPMPQMGSERMEMR
KRQMPAAQDTPGAAPGQPGAGSRGSNACCFCWCCCCSCSCLTVRNQEDQRPTIASHELRA
DLPTWEESPAPTLEEVNAWAQSFDKLMVTPAGRNAFREFLRTEFSEENMLFWMACEELKK
EANKNIIEEKARIIYEDYISILSPKEVSLDSRVREVINRNMVEPSQHIFDDAQLQIYTLM
HRDSYPRFMNSAVYKDLLQSLSEKSIEA
Function
Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds selectively to G(z)-alpha and G(alpha)-i2 subunits, accelerates their GTPase activity and regulates their signaling activities. The G(z)-alpha activity is inhibited by the phosphorylation and palmitoylation of the G-protein. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins.
Tissue Specificity Isoform 5 is expressed in brain at high levels in the caudate nucleus and temporal lobe.
Reactome Pathway
G alpha (z) signalling events (R-HSA-418597 )
G alpha (i) signalling events (R-HSA-418594 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Altered Expression [1]
Breast carcinoma DIS2UE88 Strong Altered Expression [1]
High blood pressure DISY2OHH Strong Genetic Variation [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Triple negative breast cancer DISAMG6N Strong Biomarker [1]
Bladder cancer DISUHNM0 moderate Biomarker [4]
Urinary bladder cancer DISDV4T7 moderate Biomarker [4]
Urinary bladder neoplasm DIS7HACE moderate Biomarker [4]
Substance dependence DISDRAAR Limited Genetic Variation [5]
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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
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Topotecan DMP6G8T Approved Regulator of G-protein signaling 20 (RGS20) affects the response to substance of Topotecan. [21]
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3 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 Regulator of G-protein signaling 20 (RGS20). [6]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Regulator of G-protein signaling 20 (RGS20). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Regulator of G-protein signaling 20 (RGS20). [12]
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16 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 Regulator of G-protein signaling 20 (RGS20). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Regulator of G-protein signaling 20 (RGS20). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Regulator of G-protein signaling 20 (RGS20). [9]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Regulator of G-protein signaling 20 (RGS20). [10]
Quercetin DM3NC4M Approved Quercetin increases the expression of Regulator of G-protein signaling 20 (RGS20). [7]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Regulator of G-protein signaling 20 (RGS20). [11]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Regulator of G-protein signaling 20 (RGS20). [10]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Regulator of G-protein signaling 20 (RGS20). [13]
Cytarabine DMZD5QR Approved Cytarabine increases the expression of Regulator of G-protein signaling 20 (RGS20). [14]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Regulator of G-protein signaling 20 (RGS20). [15]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Regulator of G-protein signaling 20 (RGS20). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Regulator of G-protein signaling 20 (RGS20). [17]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Regulator of G-protein signaling 20 (RGS20). [18]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Regulator of G-protein signaling 20 (RGS20). [13]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Regulator of G-protein signaling 20 (RGS20). [19]
GALLICACID DM6Y3A0 Investigative GALLICACID increases the expression of Regulator of G-protein signaling 20 (RGS20). [20]
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⏷ Show the Full List of 16 Drug(s)

References

1 Regulator of G protein signaling 20 correlates with clinicopathological features and prognosis in triple-negative breast cancer.Biochem Biophys Res Commun. 2017 Apr 8;485(3):693-697. doi: 10.1016/j.bbrc.2017.02.106. Epub 2017 Feb 22.
2 Identification of hypertension-susceptibility genes and pathways by a systemic multiple candidate gene approach: the millennium genome project for hypertension.Hypertens Res. 2008 Feb;31(2):203-12. doi: 10.1291/hypres.31.203.
3 lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR?65/RGS20 in oral squamous cell carcinoma.Oncol Rep. 2018 Apr;39(4):1948-1956. doi: 10.3892/or.2018.6283. Epub 2018 Feb 26.
4 Regulator of G protein signaling 20 promotes proliferation and migration in bladder cancer via NF-B signaling.Biomed Pharmacother. 2019 Sep;117:109112. doi: 10.1016/j.biopha.2019.109112. Epub 2019 Jun 15.
5 Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses.Behav Brain Funct. 2012 May 16;8:23. doi: 10.1186/1744-9081-8-23.
6 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.
7 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.
8 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
11 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
12 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
13 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
14 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 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.
17 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.
18 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
19 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
20 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
21 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.