Details of Drug Off-Target (DOT)

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

DOT Name Histone H2B type 1-D (H2BC5)
Synonyms H2B-clustered histone 5; HIRA-interacting protein 2; Histone H2B.1 B; Histone H2B.b; H2B/b
Gene Name H2BC5
Related Disease
Systemic lupus erythematosus ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
UniProt ID
H2B1D_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00125
Sequence
MPEPTKSAPAPKKGSKKAVTKAQKKDGKKRKRSRKESYSVYVYKVLKQVHPDTGISSKAM
GIMNSFVNDIFERIAGEASRLAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVT
KYTSSK
Function
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
KEGG Pathway
Neutrophil extracellular trap formation (hsa04613 )
Alcoholism (hsa05034 )
Viral carcinogenesis (hsa05203 )
Systemic lupus erythematosus (hsa05322 )
Reactome Pathway
Cleavage of the damaged pyrimidine (R-HSA-110329 )
Recognition and association of DNA glycosylase with site containing an affected purine (R-HSA-110330 )
Cleavage of the damaged purine (R-HSA-110331 )
Meiotic synapsis (R-HSA-1221632 )
Packaging Of Telomere Ends (R-HSA-171306 )
Pre-NOTCH Transcription and Translation (R-HSA-1912408 )
Formation of the beta-catenin (R-HSA-201722 )
PRC2 methylates histones and DNA (R-HSA-212300 )
Condensation of Prophase Chromosomes (R-HSA-2299718 )
Oxidative Stress Induced Senescence (R-HSA-2559580 )
Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582 )
DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586 )
HDACs deacetylate histones (R-HSA-3214815 )
HATs acetylate histones (R-HSA-3214847 )
SIRT1 negatively regulates rRNA expression (R-HSA-427359 )
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression (R-HSA-427389 )
NoRC negatively regulates rRNA expression (R-HSA-427413 )
B-WICH complex positively regulates rRNA expression (R-HSA-5250924 )
DNA methylation (R-HSA-5334118 )
Transcriptional regulation by small RNAs (R-HSA-5578749 )
Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472 )
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886 )
Ub-specific processing proteases (R-HSA-5689880 )
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565 )
Nonhomologous End-Joining (NHEJ) (R-HSA-5693571 )
Processing of DNA double-strand break ends (R-HSA-5693607 )
Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279 )
Assembly of the ORC complex at the origin of replication (R-HSA-68616 )
G2/M DNA damage checkpoint (R-HSA-69473 )
RNA Polymerase I Promoter Opening (R-HSA-73728 )
RNA Polymerase I Promoter Escape (R-HSA-73772 )
E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654 )
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459 )
RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236 )
Estrogen-dependent gene expression (R-HSA-9018519 )
Meiotic recombination (R-HSA-912446 )
HCMV Early Events (R-HSA-9609690 )
HCMV Late Events (R-HSA-9610379 )
Transcriptional regulation of granulopoiesis (R-HSA-9616222 )
Inhibition of DNA recombination at telomere (R-HSA-9670095 )
Defective pyroptosis (R-HSA-9710421 )
Amyloid fiber formation (R-HSA-977225 )
Chromatin modifications during the maternal to zygotic transition (MZT) (R-HSA-9821002 )
Replacement of protamines by nucleosomes in the male pronucleus (R-HSA-9821993 )
Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [1]
Breast cancer DIS7DPX1 Limited Altered Expression [2]
Breast carcinoma DIS2UE88 Limited Altered Expression [2]
Breast neoplasm DISNGJLM Limited Altered Expression [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
40 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 Histone H2B type 1-D (H2BC5). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Histone H2B type 1-D (H2BC5). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Histone H2B type 1-D (H2BC5). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Histone H2B type 1-D (H2BC5). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Histone H2B type 1-D (H2BC5). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Histone H2B type 1-D (H2BC5). [8]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Histone H2B type 1-D (H2BC5). [9]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Histone H2B type 1-D (H2BC5). [10]
Quercetin DM3NC4M Approved Quercetin increases the expression of Histone H2B type 1-D (H2BC5). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Histone H2B type 1-D (H2BC5). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Histone H2B type 1-D (H2BC5). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Histone H2B type 1-D (H2BC5). [14]
Testosterone DM7HUNW Approved Testosterone increases the expression of Histone H2B type 1-D (H2BC5). [14]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Histone H2B type 1-D (H2BC5). [9]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Histone H2B type 1-D (H2BC5). [15]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Histone H2B type 1-D (H2BC5). [16]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Histone H2B type 1-D (H2BC5). [17]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Histone H2B type 1-D (H2BC5). [18]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Histone H2B type 1-D (H2BC5). [19]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Histone H2B type 1-D (H2BC5). [20]
Nicotine DMWX5CO Approved Nicotine increases the expression of Histone H2B type 1-D (H2BC5). [21]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Histone H2B type 1-D (H2BC5). [22]
Berberine DMC5Q8X Phase 4 Berberine decreases the expression of Histone H2B type 1-D (H2BC5). [23]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Histone H2B type 1-D (H2BC5). [24]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Histone H2B type 1-D (H2BC5). [25]
Curcumin DMQPH29 Phase 3 Curcumin increases the expression of Histone H2B type 1-D (H2BC5). [26]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Histone H2B type 1-D (H2BC5). [25]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Histone H2B type 1-D (H2BC5). [24]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Histone H2B type 1-D (H2BC5). [27]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Histone H2B type 1-D (H2BC5). [28]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Histone H2B type 1-D (H2BC5). [29]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 decreases the expression of Histone H2B type 1-D (H2BC5). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Histone H2B type 1-D (H2BC5). [25]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Histone H2B type 1-D (H2BC5). [30]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Histone H2B type 1-D (H2BC5). [16]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Histone H2B type 1-D (H2BC5). [31]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Histone H2B type 1-D (H2BC5). [32]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Histone H2B type 1-D (H2BC5). [33]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of Histone H2B type 1-D (H2BC5). [34]
Propanoic Acid DM9TN2W Investigative Propanoic Acid decreases the expression of Histone H2B type 1-D (H2BC5). [35]
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⏷ Show the Full List of 40 Drug(s)

References

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2 A Role for Histone H2B Variants in Endocrine-Resistant Breast Cancer.Horm Cancer. 2015 Dec;6(5-6):214-24. doi: 10.1007/s12672-015-0230-5. Epub 2015 Jun 26.
3 Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
4 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.
5 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
6 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.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 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.
10 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
11 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.
12 Synergistic effects of arsenic trioxide combined with ascorbic acid in human osteosarcoma MG-63 cells: a systems biology analysis. Eur Rev Med Pharmacol Sci. 2014;18(24):3877-88.
13 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
14 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
15 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
17 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
18 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
19 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
20 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
21 Downregulation of Stem-Loop Binding Protein by Nicotine via 7-Nicotinic Acetylcholine Receptor and Its Role in Nicotine-Induced Cell Transformation. Toxicol Sci. 2022 Sep 24;189(2):186-202. doi: 10.1093/toxsci/kfac080.
22 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
23 Berberine acts as a putative epigenetic modulator by affecting the histone code. Toxicol In Vitro. 2016 Oct;36:10-17. doi: 10.1016/j.tiv.2016.06.004. Epub 2016 Jun 13.
24 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.
25 Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
26 Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
27 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
28 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
29 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.
30 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.
31 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
32 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
33 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.
34 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
35 Propionic acid induces mitochondrial dysfunction and affects gene expression for mitochondria biogenesis and neuronal differentiation in SH-SY5Y cell line. Neurotoxicology. 2019 Dec;75:116-122. doi: 10.1016/j.neuro.2019.09.009. Epub 2019 Sep 14.