Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCWTAX0)

DOT Name	E3 ubiquitin-protein ligase RING1 (RING1)
Synonyms	EC 2.3.2.27; Polycomb complex protein RING1; RING finger protein 1; RING-type E3 ubiquitin transferase RING1; Really interesting new gene 1 protein
Gene Name	RING1
Related Disease	Acute myelogenous leukaemia ( ) Hepatitis B virus infection ( ) Acute monocytic leukemia ( ) Anca-associated vasculitis ( ) Bladder cancer ( ) Classic Hodgkin lymphoma ( ) Colorectal carcinoma ( ) Follicular lymphoma ( ) Hypertrophic cardiomyopathy ( ) Lung cancer ( ) Lung carcinoma ( ) Mantle cell lymphoma ( ) Myelodysplastic syndrome ( ) Neoplasm ( ) Non-hodgkin lymphoma ( ) Non-small-cell lung cancer ( ) Prostate cancer ( ) Prostate carcinoma ( ) Prostate neoplasm ( ) Renal cell carcinoma ( ) Transitional cell carcinoma ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Urothelial carcinoma ( ) Advanced cancer ( ) Hepatocellular carcinoma ( ) Parkinson disease ( ) Complex neurodevelopmental disorder ( ) Melanoma ( )
UniProt ID	RING1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.3.2.27
Pfam ID	PF16207 ; PF13923
Sequence	MTTPANAQNASKTWELSLYELHRTPQEAIMDGTEIAVSPRSLHSELMCPICLDMLKNTMT TKECLHRFCSDCIVTALRSGNKECPTCRKKLVSKRSLRPDPNFDALISKIYPSREEYEAH QDRVLIRLSRLHNQQALSSSIEEGLRMQAMHRAQRVRRPIPGSDQTTTMSGGEGEPGEGE GDGEDVSSDSAPDSAPGPAPKRPRGGGAGGSSVGTGGGGTGGVGGGAGSEDSGDRGGTLG GGTLGPPSPPGAPSPPEPGGEIELVFRPHPLLVEKGEYCQTRYVKTTGNATVDHLSKYLA LRIALERRQQQEAGEPGGPGGGASDTGGPDGCGGEGGGAGGGDGPEEPALPSLEGVSEKQ YTIYIAPGGGAFTTLNGSLTLELVNEKFWKVSRPLELCYAPTKDPK
Function	Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity.
KEGG Pathway	Polycomb repressive complex (hsa03083 )
Reactome Pathway	SUMOylation of DNA damage response and repair proteins (R-HSA-3108214 ) SUMOylation of transcription cofactors (R-HSA-3899300 ) SUMOylation of chromatin organization proteins (R-HSA-4551638 ) SUMOylation of RNA binding proteins (R-HSA-4570464 ) SUMOylation of DNA methylation proteins (R-HSA-4655427 ) RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243 ) Regulation of PTEN gene transcription (R-HSA-8943724 ) Transcriptional Regulation by E2F6 (R-HSA-8953750 ) Oxidative Stress Induced Senescence (R-HSA-2559580 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Hepatitis B virus infection	DISLQ2XY	Definitive	Genetic Variation	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[3]
Anca-associated vasculitis	DISU3CNU	Strong	Genetic Variation	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Follicular lymphoma	DISVEUR6	Strong	Genetic Variation	[8]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[9]
Lung cancer	DISCM4YA	Strong	Altered Expression	[10]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[10]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[11]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[15]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[16]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[10]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[10]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[17]
Parkinson disease	DISQVHKL	Disputed	Genetic Variation	[18]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Unknown	[19]
Melanoma	DIS1RRCY	Limited	Biomarker	[20]
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⏷ Show the Full List of 29 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

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
Cisplatin	DMRHGI9	Approved	E3 ubiquitin-protein ligase RING1 (RING1) affects the response to substance of Cisplatin.	[26]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of E3 ubiquitin-protein ligase RING1 (RING1).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of E3 ubiquitin-protein ligase RING1 (RING1).	[22]
Selenium	DM25CGV	Approved	Selenium increases the expression of E3 ubiquitin-protein ligase RING1 (RING1).	[24]
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3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of E3 ubiquitin-protein ligase RING1 (RING1).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of E3 ubiquitin-protein ligase RING1 (RING1).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of E3 ubiquitin-protein ligase RING1 (RING1).	[23]
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References

1	Association between single nucleotide polymorphisms within HLA region and disease relapse for patients with hematopoietic stem cell transplantation.Sci Rep. 2019 Sep 24;9(1):13731. doi: 10.1038/s41598-019-50111-5.
2	A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population.Hum Mol Genet. 2011 Oct 1;20(19):3884-92. doi: 10.1093/hmg/ddr301. Epub 2011 Jul 12.
3	Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells.Blood. 2018 Apr 19;131(16):1833-1845. doi: 10.1182/blood-2017-05-787226. Epub 2018 Jan 25.
4	The Wegener's granulomatosis quantitative trait locus on chromosome 6p21.3 as characterised by tagSNP genotyping.Ann Rheum Dis. 2008 Jul;67(7):972-9. doi: 10.1136/ard.2007.077693. Epub 2007 Oct 29.
5	Upregulated expression of polycomb protein Ring1 contributes to poor prognosis and accelerated proliferation in human hepatocellular carcinoma.Tumour Biol. 2015 Dec;36(12):9579-88. doi: 10.1007/s13277-015-3721-7. Epub 2015 Jul 4.
6	Abnormal PcG protein expression in Hodgkin's lymphoma. Relation with E2F6 and NFkappaB transcription factors.J Pathol. 2004 Dec;204(5):528-37. doi: 10.1002/path.1661.
7	The E3 Ligase RING1 Targets p53 for Degradation and Promotes Cancer Cell Proliferation and Survival.Cancer Res. 2018 Jan 15;78(2):359-371. doi: 10.1158/0008-5472.CAN-17-1805. Epub 2017 Nov 29.
8	Variations in chromosomes 9 and 6p21.3 with risk of non-Hodgkin lymphoma.Cancer Epidemiol Biomarkers Prev. 2011 Jan;20(1):42-9. doi: 10.1158/1055-9965.EPI-10-0638. Epub 2010 Dec 10.
9	Human molecular genetic and functional studies identify TRIM63, encoding Muscle RING Finger Protein 1, as a novel gene for human hypertrophic cardiomyopathy.Circ Res. 2012 Sep 14;111(7):907-19. doi: 10.1161/CIRCRESAHA.112.270207. Epub 2012 Jul 19.
10	Polycomb group oncogene RING1 is over-expressed in non-small cell lung cancer.Pathol Oncol Res. 2014 Jul;20(3):549-56. doi: 10.1007/s12253-013-9727-9. Epub 2014 Jan 11.
11	The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma.Br J Haematol. 2001 Mar;112(4):950-8. doi: 10.1046/j.1365-2141.2001.02641.x.
12	Polycomb protein RING1A limits hematopoietic differentiation in myelodysplastic syndromes.Oncotarget. 2017 Dec 1;8(70):115002-115017. doi: 10.18632/oncotarget.22839. eCollection 2017 Dec 29.
13	Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B.Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):E6332-E6341. doi: 10.1073/pnas.1619932114. Epub 2017 Jul 18.
14	Down-regulation of lncRNA XIST inhibits cell proliferation via regulating miR-744/RING1 axis in non-small cell lung cancer.Clin Sci (Lond). 2019 Jul 18;133(14):1567-1579. doi: 10.1042/CS20190519. Print 2019 Jul 31.
15	Polycomb-group oncogenes EZH2, BMI1, and RING1 are overexpressed in prostate cancer with adverse pathologic and clinical features.Eur Urol. 2007 Aug;52(2):455-63. doi: 10.1016/j.eururo.2006.11.020. Epub 2006 Nov 17.
16	Variability in the expression of polycomb proteins in different normal and tumoral tissues. A pilot study using tissue microarrays.Mod Pathol. 2006 May;19(5):684-94. doi: 10.1038/modpathol.3800577.
17	Ring1 promotes the transformation of hepatic progenitor cells into cancer stem cells through the Wnt/-catenin signaling pathway.J Cell Biochem. 2020 Aug;121(8-9):3941-3951. doi: 10.1002/jcb.29496. Epub 2019 Nov 7.
18	Interaction between RING1 (R1) and the Ubiquitin-like (UBL) Domains Is Critical for the Regulation of Parkin Activity.J Biol Chem. 2016 Jan 22;291(4):1803-1816. doi: 10.1074/jbc.M115.687319. Epub 2015 Dec 2.
19	De novo mutation in RING1 with epigenetic effects on neurodevelopment. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1558-1563. doi: 10.1073/pnas.1721290115. Epub 2018 Jan 31.
20	Nuclear envelope-distributed CD147 interacts with and inhibits the transcriptional function of RING1 and promotes melanoma cell motility.PLoS One. 2017 Aug 23;12(8):e0183689. doi: 10.1371/journal.pone.0183689. eCollection 2017.
21	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.
22	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.
23	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.
24	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.
25	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
26	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.