General Information of Drug Off-Target (DOT) (ID: OTQ450A3)

DOT Name Histone H1.4 (H1-4)
Synonyms Histone H1b; Histone H1s-4
Gene Name H1-4
Related Disease
Rahman syndrome ( )
Syndromic intellectual disability ( )
Autism ( )
Autism spectrum disorder ( )
Intellectual disability ( )
Pancreatic cancer ( )
Pervasive developmental disorder ( )
Premature aging syndrome ( )
Schizophrenia ( )
Overgrowth syndrome ( )
UniProt ID
H14_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3TZD; 5JJZ; 6H8P; 7K5Y; 7K63; 7PET; 7PEU; 7PEX; 7PEZ; 7PF0; 7PF2; 7PF3; 7PF5; 7PF6; 7PFA; 7PFC; 7PFD; 7PFE; 7PFT; 7PFU; 7PFV; 7PFW; 7PFX; 8H1T
Pfam ID
PF00538
Sequence
MSETAPAAPAAPAPAEKTPVKKKARKSAGAAKRKASGPPVSELITKAVAASKERSGVSLA
ALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGEAKPKA
KKAGAAKAKKPAGAAKKPKKATGAATPKKSAKKTPKKAKKPAAAAGAKKAKSPKKAKAAK
PKKAPKSPAKAKAVKPKAAKPKTAKPKAAKPKKAAAKKK
Function
Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation.
Reactome Pathway
Formation of Senescence-Associated Heterochromatin Foci (SAHF) (R-HSA-2559584 )
Apoptosis induced DNA fragmentation (R-HSA-140342 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Rahman syndrome DIS35M1T Definitive Autosomal dominant [1]
Syndromic intellectual disability DISH7SDF Definitive Autosomal dominant [2]
Autism DISV4V1Z Strong Biomarker [3]
Autism spectrum disorder DISXK8NV Strong Genetic Variation [3]
Intellectual disability DISMBNXP Strong Genetic Variation [1]
Pancreatic cancer DISJC981 Strong Biomarker [4]
Pervasive developmental disorder DIS51975 Strong Genetic Variation [3]
Premature aging syndrome DIS51AGT Strong Biomarker [5]
Schizophrenia DISSRV2N Strong Biomarker [6]
Overgrowth syndrome DISHK54G Limited Biomarker [7]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
22 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 H1.4 (H1-4). [8]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Histone H1.4 (H1-4). [9]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Histone H1.4 (H1-4). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Histone H1.4 (H1-4). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Histone H1.4 (H1-4). [12]
Menadione DMSJDTY Approved Menadione affects the expression of Histone H1.4 (H1-4). [13]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Histone H1.4 (H1-4). [14]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of Histone H1.4 (H1-4). [15]
Lucanthone DMZLBUO Approved Lucanthone decreases the expression of Histone H1.4 (H1-4). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Histone H1.4 (H1-4). [17]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of Histone H1.4 (H1-4). [18]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Histone H1.4 (H1-4). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Histone H1.4 (H1-4). [20]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Histone H1.4 (H1-4). [21]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Histone H1.4 (H1-4). [22]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the expression of Histone H1.4 (H1-4). [18]
UNC0379 DMD1E4J Preclinical UNC0379 decreases the expression of Histone H1.4 (H1-4). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Histone H1.4 (H1-4). [24]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Histone H1.4 (H1-4). [25]
Paraquat DMR8O3X Investigative Paraquat decreases the expression of Histone H1.4 (H1-4). [26]
Okadaic acid DM47CO1 Investigative Okadaic acid decreases the expression of Histone H1.4 (H1-4). [27]
Bilirubin DMI0V4O Investigative Bilirubin increases the expression of Histone H1.4 (H1-4). [28]
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⏷ Show the Full List of 22 Drug(s)

References

1 HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals. Am J Med Genet A. 2019 Oct;179(10):2049-2055. doi: 10.1002/ajmg.a.61321. Epub 2019 Aug 9.
2 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
3 Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review.Am J Med Genet B Neuropsychiatr Genet. 2018 Jun;177(4):426-433. doi: 10.1002/ajmg.b.32631. Epub 2018 Apr 27.
4 Purification and partial sequencing of inhibitory factor on renal membrane adenylate cyclase in pancreatic cancer extract: identity with histones H1b or H1d.Biochem Biophys Res Commun. 1991 Apr 15;176(1):255-61. doi: 10.1016/0006-291x(91)90917-v.
5 Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging.Am J Hum Genet. 2019 Sep 5;105(3):493-508. doi: 10.1016/j.ajhg.2019.07.007. Epub 2019 Aug 22.
6 Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia.Mol Psychiatry. 2015 Apr;20(4):424-32. doi: 10.1038/mp.2014.63. Epub 2014 Jul 22.
7 Growth pattern of Rahman syndrome.Am J Med Genet A. 2018 Mar;176(3):712-714. doi: 10.1002/ajmg.a.38616. Epub 2018 Jan 31.
8 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 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.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
13 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.
14 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
15 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
16 Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
17 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
18 Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
19 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
20 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.
21 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
22 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.
23 Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
24 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
25 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.
26 An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.
27 Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.
28 Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.