Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU0F4LL)

DOT Name Histone-lysine N-methyltransferase SUV39H2 (SUV39H2)
Synonyms EC 2.1.1.355; Histone H3-K9 methyltransferase 2; H3-K9-HMTase 2; Lysine N-methyltransferase 1B; Suppressor of variegation 3-9 homolog 2; Su(var)3-9 homolog 2
Gene Name SUV39H2
Related Disease
Adult hepatocellular carcinoma ( )
Advanced cancer ( )
Bone cancer ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Fatty liver disease ( )
Gastric cancer ( )
Glioma ( )
Graves disease ( )
Hepatitis C virus infection ( )
leukaemia ( )
Leukemia ( )
Liver cancer ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Lymphoma ( )
Migraine disorder ( )
Osteosarcoma ( )
Stomach cancer ( )
Systemic sclerosis ( )
Neoplasm ( )
Pemphigus vulgaris ( )
Chromosomal disorder ( )
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Nasopharyngeal carcinoma ( )
Non-alcoholic steatohepatitis ( )
Small lymphocytic lymphoma ( )
Type-1 diabetes ( )
UniProt ID
SUV92_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2R3A; 6P0R
EC Number
2.1.1.355
Pfam ID
PF00385 ; PF05033 ; PF00856
Sequence
MAAVGAEARGAWCVPCLVSLDTLQELCRKEKLTCKSIGITKRNLNNYEVEYLCDYKVVKD
MEYYLVKWKGWPDSTNTWEPLQNLKCPLLLQQFSNDKHNYLSQVKKGKAITPKDNNKTLK
PAIAEYIVKKAKQRIALQRWQDELNRRKNHKGMIFVENTVDLEGPPSDFYYINEYKPAPG
ISLVNEATFGCSCTDCFFQKCCPAEAGVLLAYNKNQQIKIPPGTPIYECNSRCQCGPDCP
NRIVQKGTQYSLCIFRTSNGRGWGVKTLVKIKRMSFVMEYVGEVITSEEAERRGQFYDNK
GITYLFDLDYESDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDTRLPRIALFSTR
TINAGEELTFDYQMKGSGDISSDSIDHSPAKKRVRTVCKCGAVTCRGYLN
Function
Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as cell cycle regulation, transcriptional repression and regulation of telomere length. May participate in regulation of higher-order chromatin organization during spermatogenesis. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.
KEGG Pathway
Lysine degradation (hsa00310 )
Metabolic pathways (hsa01100 )
Reactome Pathway
PKMTs methylate histone lysines (R-HSA-3214841 )
BioCyc Pathway
MetaCyc:HS07820-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult hepatocellular carcinoma DIS6ZPAI Strong Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Bone cancer DIS38NA0 Strong Altered Expression [2]
Bone osteosarcoma DIST1004 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Altered Expression [1]
Breast carcinoma DIS2UE88 Strong Altered Expression [1]
Fatty liver disease DIS485QZ Strong Biomarker [3]
Gastric cancer DISXGOUK Strong Altered Expression [1]
Glioma DIS5RPEH Strong Biomarker [4]
Graves disease DISU4KOQ Strong Altered Expression [5]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [6]
leukaemia DISS7D1V Strong Altered Expression [1]
Leukemia DISNAKFL Strong Altered Expression [1]
Liver cancer DISDE4BI Strong Altered Expression [1]
Lung adenocarcinoma DISD51WR Strong Biomarker [7]
Lung cancer DISCM4YA Strong Altered Expression [1]
Lung carcinoma DISTR26C Strong Altered Expression [1]
Lung neoplasm DISVARNB Strong Genetic Variation [8]
Lymphoma DISN6V4S Strong Altered Expression [1]
Migraine disorder DISFCQTG Strong Genetic Variation [9]
Osteosarcoma DISLQ7E2 Strong Biomarker [2]
Stomach cancer DISKIJSX Strong Altered Expression [1]
Systemic sclerosis DISF44L6 Strong Altered Expression [10]
Neoplasm DISZKGEW moderate Biomarker [7]
Pemphigus vulgaris DISENR62 moderate Biomarker [11]
Chromosomal disorder DISM5BB5 Limited Altered Expression [12]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [1]
Hepatocellular carcinoma DIS0J828 Limited Altered Expression [1]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [13]
Non-alcoholic steatohepatitis DIST4788 Limited Biomarker [14]
Small lymphocytic lymphoma DIS30POX Limited Altered Expression [12]
Type-1 diabetes DIS7HLUB Limited Biomarker [15]
------------------------------------------------------------------------------------
⏷ Show the Full List of 32 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [16]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [28]
------------------------------------------------------------------------------------
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [17]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [18]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [19]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [20]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [21]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [22]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [22]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [23]
Nitric Oxide DM1RBYG Approved Nitric Oxide increases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [24]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [25]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [26]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [27]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Histone-lysine N-methyltransferase SUV39H2 (SUV39H2). [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 Drug(s)

References

1 The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View.J Cancer. 2019 Jan 1;10(3):721-729. doi: 10.7150/jca.28254. eCollection 2019.
2 Histone methyltransferase SUV39H2 serves oncogenic roles in osteosarcoma.Oncol Rep. 2019 Jan;41(1):325-332. doi: 10.3892/or.2018.6843. Epub 2018 Nov 1.
3 Suv39h2 deficiency ameliorates diet-induced steatosis in mice.Biochem Biophys Res Commun. 2017 Apr 8;485(3):658-664. doi: 10.1016/j.bbrc.2017.02.093. Epub 2017 Feb 21.
4 Histone methyltransferase SUV39H2 regulates cell growth and chemosensitivity in glioma via regulation of hedgehog signaling.Cancer Cell Int. 2019 Oct 16;19:269. doi: 10.1186/s12935-019-0982-z. eCollection 2019.
5 Aberrant Histone Methylation in Patients with Graves' Disease.Int J Endocrinol. 2019 Jun 24;2019:1454617. doi: 10.1155/2019/1454617. eCollection 2019.
6 Histone-modifying genes as biomarkers in hepatocellular carcinoma.Int J Clin Exp Pathol. 2014 Apr 15;7(5):2496-507. eCollection 2014.
7 Identification of SUV39H2 as a potential oncogene in lung adenocarcinoma.Clin Epigenetics. 2018 Oct 22;10(1):129. doi: 10.1186/s13148-018-0562-4.
8 Novel polymorphisms in the SUV39H2 histone methyltransferase and the risk of lung cancer.Carcinogenesis. 2006 Nov;27(11):2217-22. doi: 10.1093/carcin/bgl084. Epub 2006 Jun 13.
9 Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
10 Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis.Clin Immunol. 2013 Oct;149(1):46-54. doi: 10.1016/j.clim.2013.06.006. Epub 2013 Jun 20.
11 Aberrant epigenetic modifications in peripheral blood mononuclear cells from patients with pemphigus vulgaris.Br J Dermatol. 2012 Sep;167(3):523-31. doi: 10.1111/j.1365-2133.2012.11007.x. Epub 2012 Aug 10.
12 Aberrant levels of SUV39H1 and SUV39H2 methyltransferase are associated with genomic instability in chronic lymphocytic leukemia.Environ Mol Mutagen. 2017 Dec;58(9):654-661. doi: 10.1002/em.22128. Epub 2017 Aug 19.
13 Elevated SUV39H2 attributes to the progression of nasopharyngeal carcinoma via regulation of NRIP1.Biochem Biophys Res Commun. 2019 Mar 5;510(2):290-295. doi: 10.1016/j.bbrc.2019.01.092. Epub 2019 Jan 30.
14 The histone methyltransferase Suv39h2 contributes to nonalcoholic steatohepatitis in mice.Hepatology. 2017 Jun;65(6):1904-1919. doi: 10.1002/hep.29127. Epub 2017 Apr 28.
15 Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes.Diabetes. 2011 Nov;60(11):3073-80. doi: 10.2337/db11-0073. Epub 2011 Sep 6.
16 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.
17 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
18 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
19 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
20 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
21 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.
22 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
23 Alcohol triggered bile acid disequilibrium by suppressing BSEP to sustain hepatocellular carcinoma progression. Chem Biol Interact. 2022 Apr 1;356:109847. doi: 10.1016/j.cbi.2022.109847. Epub 2022 Feb 9.
24 Nitric oxide modifies global histone methylation by inhibiting Jumonji C domain-containing demethylases. J Biol Chem. 2013 May 31;288(22):16004-15. doi: 10.1074/jbc.M112.432294. Epub 2013 Apr 1.
25 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
26 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.
27 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
28 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.