Details of Drug Off-Target (DOT)

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

DOT Name Histone H3.1 (H3C1)
Synonyms Histone H3/a; Histone H3/b; Histone H3/c; Histone H3/d; Histone H3/f; Histone H3/h; Histone H3/i; Histone H3/j; Histone H3/k; Histone H3/l
Gene Name H3C1
Related Disease
Advanced cancer ( )
Brain neoplasm ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Gastrointestinal stromal tumour ( )
Glioblastoma multiforme ( )
Glioma ( )
Glioma susceptibility 1 ( )
Liver cancer ( )
Lung squamous cell carcinoma ( )
Medulloblastoma ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Autoimmune polyendocrinopathy ( )
Lung cancer ( )
Lung carcinoma ( )
Venous thromboembolism ( )
UniProt ID
H31_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1CS9 ; 1CT6 ; 1O9S ; 1Q3L ; 2B2T ; 2B2U ; 2B2V ; 2B2W ; 2C1J ; 2C1N ; 2CO0 ; 2CV5 ; 2FSA ; 2KWJ ; 2KWK ; 2L75 ; 2LBM ; 2LGG ; 2M0O ; 2NDF ; 2NDG ; 2OQ6 ; 2OT7 ; 2OX0 ; 2RI7 ; 2RR4 ; 2UXN ; 2V85 ; 2V89 ; 2VNF ; 2VPG ; 2X0L ; 3A1B ; 3AFA ; 3AVR ; 3AYW ; 3AZE ; 3AZF ; 3AZG ; 3AZH ; 3AZI ; 3AZJ ; 3AZK ; 3AZL ; 3AZM ; 3AZN ; 3B95 ; 3FDT ; 3KMT ; 3KQI ; 3LQI ; 3LQJ ; 3MP1 ; 3O34 ; 3O35 ; 3O37 ; 3QJ6 ; 3RIG ; 3RIY ; 3SOU ; 3SOW ; 3U31 ; 3U3D ; 3U4S ; 3U5N ; 3U5O ; 3U5P ; 3UEE ; 3UEF ; 3UIG ; 3UII ; 3UIK ; 3V43 ; 3W96 ; 3W97 ; 3W98 ; 3W99 ; 3WA9 ; 3WAA ; 3WKJ ; 3X1S ; 3X1T ; 3X1U ; 3X1V ; 3ZG6 ; 3ZVY ; 4A0J ; 4A0N ; 4A7J ; 4BD3 ; 4C1Q ; 4F4U ; 4F56 ; 4FWF ; 4HON ; 4I51 ; 4L7X ; 4LK9 ; 4LKA ; 4LLB ; 4LXL ; 4N4H ; 4QBQ ; 4QBR ; 4QBS ; 4TN7 ; 4U68 ; 4UP0 ; 4UY4 ; 4X3K ; 4Y6L ; 4YHP ; 4YHZ ; 4YM5 ; 4YM6 ; 4Z0R ; 4Z2M ; 5AV5 ; 5AV6 ; 5AV8 ; 5AV9 ; 5AVB ; 5AVC ; 5B24 ; 5B2I ; 5B2J ; 5B31 ; 5C11 ; 5C13 ; 5C3I ; 5CPI ; 5CPJ ; 5CPK ; 5D6Y ; 5DAH ; 5FB0 ; 5FB1 ; 5FFV ; 5GH9 ; 5GSE ; 5GSU ; 5GT0 ; 5GT3 ; 5GTC ; 5H6Q ; 5H6R ; 5HJB ; 5HJC ; 5HJD ; 5HYN ; 5IQL ; 5J3V ; 5J9S ; 5JHN ; 5JIN ; 5JIY ; 5JJ0 ; 5JRG ; 5KJH ; 5KJI ; 5KKL ; 5LUG ; 5M5G ; 5MR8 ; 5NNC ; 5NND ; 5OY3 ; 5SVX ; 5SVY ; 5SZB ; 5SZC ; 5T0K ; 5T0M ; 5T1G ; 5T1I ; 5T8R ; 5TBN ; 5TDR ; 5TDW ; 5U2J ; 5V21 ; 5V22 ; 5VA6 ; 5VAB ; 5VGE ; 5VNB ; 5WFC ; 5WLE ; 5WVO ; 5WXG ; 5WXH ; 5WYI ; 5X60 ; 5XF3 ; 5XF4 ; 5XF5 ; 5XFQ ; 5XFR ; 5XNV ; 5XTZ ; 5Y0C ; 5Y0D ; 5Y20 ; 5Y2F ; 5Z23 ; 5Z30 ; 6AXJ ; 6AZE ; 6BHD ; 6BHE ; 6BHG ; 6BHH ; 6BHI ; 6D07 ; 6D08 ; 6E83 ; 6E86 ; 6F6D ; 6HKT ; 6HTS ; 6IEU ; 6IIS ; 6IIT ; 6IPU ; 6IQ4 ; 6JOU ; 6JR0 ; 6JR1 ; 6JXD ; 6K1I ; 6K1J ; 6K1K ; 6KE9 ; 6KVD ; 6L49 ; 6L4A ; 6L9H ; 6L9Z ; 6LA2 ; 6LA8 ; 6LA9 ; 6LAB ; 6LE9 ; 6LER ; 6LS6 ; 6LSD ; 6M3V ; 6M44 ; 6M4D ; 6M4G ; 6M4H ; 6MIL ; 6MIM ; 6MIN ; 6MIO ; 6MIQ ; 6PA1 ; 6PAG ; 6R8Y ; 6R8Z ; 6R90 ; 6R91 ; 6R92 ; 6R93 ; 6R94 ; 6T90 ; 6T93 ; 6UPK ; 6UPL ; 6USJ ; 6V2H ; 6V2K ; 6V3N ; 6V41 ; 6V92 ; 6VIL ; 6WAV ; 6WW4 ; 6YIF ; 6YIH ; 6YOV ; 7BWD ; 7C0M ; 7CCQ ; 7CCR ; 7CFP ; 7CFQ ; 7COW ; 7D1Z ; 7DBP ; 7E8D ; 7EBK ; 7K5X ; 7K5Y ; 7K60 ; 7K61 ; 7K63 ; 7KLR ; 7LBK ; 7LBO ; 7LBP ; 7LBQ ; 7LYA ; 7LYB ; 7LYC ; 7MJU ; 7NL0 ; 7SCY ; 7SCZ ; 7TD5 ; 7U0G ; 7U0I ; 7U0J ; 7V6Q ; 7V90 ; 7V96 ; 7V9C ; 7V9J ; 7V9K ; 7V9S ; 7VA4 ; 7VZ4 ; 7W9V ; 7X57 ; 7X58 ; 7XD1 ; 7XVL ; 7XVM ; 7XX5 ; 7XX6 ; 7XX7 ; 7XZX ; 7XZY ; 7XZZ ; 7Y00 ; 7Y5U ; 7Y5V ; 7Y5W ; 7Y60 ; 7Y61 ; 7Y7I ; 7Y8R ; 7YOZ ; 7YQK ; 7ZI4 ; 8DK5 ; 8EVG ; 8EVH ; 8EVI ; 8EVJ ; 8GRM ; 8GUI ; 8GUJ ; 8GUK ; 8H0V ; 8H0W ; 8H1T ; 8HAG ; 8HAH ; 8HAI ; 8HAJ ; 8HAK ; 8HAL ; 8HAM ; 8HAN ; 8HE5 ; 8I60 ; 8IEG ; 8IEJ ; 8IIY ; 8IIZ ; 8IJ0 ; 8IQF ; 8IQG ; 8J6S ; 8J6T ; 8JHF ; 8JHG ; 8JL9 ; 8JLA ; 8OFF ; 8OO7 ; 8OOA ; 8OOP ; 8OOS ; 8OSJ ; 8OSK ; 8OSL ; 8OTS ; 8OTT ; 8OX0 ; 8OX1 ; 8QKT ; 8SPS ; 8SPU ; 8SYP
Pfam ID
PF00125
Sequence
MARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTE
LLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEACEAYLVGLFEDTNLCAIHAKRVTI
MPKDIQLARRIRGERA
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 )
Shigellosis (hsa05131 )
Transcriptio.l misregulation in cancer (hsa05202 )
Systemic lupus erythematosus (hsa05322 )
Reactome Pathway
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 )
HDACs deacetylate histones (R-HSA-3214815 )
PKMTs methylate histone lysines (R-HSA-3214841 )
HDMs demethylate histones (R-HSA-3214842 )
HATs acetylate histones (R-HSA-3214847 )
RMTs methylate histone arginines (R-HSA-3214858 )
Chromatin modifying enzymes (R-HSA-3247509 )
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 )
Assembly of the ORC complex at the origin of replication (R-HSA-68616 )
RNA Polymerase I Promoter Opening (R-HSA-73728 )
RNA Polymerase I Promoter Escape (R-HSA-73772 )
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 )
Defective pyroptosis (R-HSA-9710421 )
Amyloid fiber formation (R-HSA-977225 )
Chromatin modifications during the maternal to zygotic transition (MZT) (R-HSA-9821002 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
Interleukin-7 signaling (R-HSA-1266695 )

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Brain neoplasm DISY3EKS Strong Biomarker [2]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Altered Expression [3]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [3]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [4]
Gastrointestinal stromal tumour DIS6TJYS Strong Altered Expression [3]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [5]
Glioma DIS5RPEH Strong Genetic Variation [6]
Glioma susceptibility 1 DISD5L1R Strong Genetic Variation [7]
Liver cancer DISDE4BI Strong Altered Expression [3]
Lung squamous cell carcinoma DISXPIBD Strong Genetic Variation [3]
Medulloblastoma DISZD2ZL Strong Genetic Variation [8]
Neoplasm DISZKGEW Strong Genetic Variation [2]
Ovarian cancer DISZJHAP Strong Biomarker [4]
Ovarian neoplasm DISEAFTY Strong Biomarker [4]
Parkinson disease DISQVHKL Strong Biomarker [9]
Autoimmune polyendocrinopathy DISOLDB2 Limited Biomarker [10]
Lung cancer DISCM4YA Limited Altered Expression [11]
Lung carcinoma DISTR26C Limited Altered Expression [11]
Venous thromboembolism DISUR7CR Limited Biomarker [12]
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⏷ Show the Full List of 20 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Histone H3.1 (H3C1). [13]
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Histone H3.1 (H3C1). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Histone H3.1 (H3C1). [44]
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41 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Histone H3.1 (H3C1). [14]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Histone H3.1 (H3C1). [15]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Histone H3.1 (H3C1). [16]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Histone H3.1 (H3C1). [17]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Histone H3.1 (H3C1). [18]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Histone H3.1 (H3C1). [19]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Histone H3.1 (H3C1). [20]
Quercetin DM3NC4M Approved Quercetin increases the expression of Histone H3.1 (H3C1). [22]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Histone H3.1 (H3C1). [23]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Histone H3.1 (H3C1). [24]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Histone H3.1 (H3C1). [25]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Histone H3.1 (H3C1). [24]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Histone H3.1 (H3C1). [26]
Menadione DMSJDTY Approved Menadione affects the expression of Histone H3.1 (H3C1). [27]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Histone H3.1 (H3C1). [28]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Histone H3.1 (H3C1). [29]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Histone H3.1 (H3C1). [30]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Histone H3.1 (H3C1). [31]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Histone H3.1 (H3C1). [32]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Histone H3.1 (H3C1). [33]
Nicotine DMWX5CO Approved Nicotine increases the expression of Histone H3.1 (H3C1). [34]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate increases the expression of Histone H3.1 (H3C1). [35]
Lucanthone DMZLBUO Approved Lucanthone decreases the expression of Histone H3.1 (H3C1). [36]
Aminoglutethimide DMWFHMZ Approved Aminoglutethimide increases the expression of Histone H3.1 (H3C1). [37]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Histone H3.1 (H3C1). [38]
Berberine DMC5Q8X Phase 4 Berberine decreases the expression of Histone H3.1 (H3C1). [39]
Isoflavone DM7U58J Phase 4 Isoflavone affects the expression of Histone H3.1 (H3C1). [40]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Histone H3.1 (H3C1). [25]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Histone H3.1 (H3C1). [28]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Histone H3.1 (H3C1). [41]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of Histone H3.1 (H3C1). [42]
PEITC DMOMN31 Phase 2 PEITC decreases the expression of Histone H3.1 (H3C1). [43]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Histone H3.1 (H3C1). [45]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Histone H3.1 (H3C1). [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Histone H3.1 (H3C1). [47]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Histone H3.1 (H3C1). [48]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Histone H3.1 (H3C1). [49]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Histone H3.1 (H3C1). [50]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Histone H3.1 (H3C1). [51]
Paraquat DMR8O3X Investigative Paraquat decreases the expression of Histone H3.1 (H3C1). [52]
Resorcinol DMM37C0 Investigative Resorcinol decreases the expression of Histone H3.1 (H3C1). [32]
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⏷ Show the Full List of 41 Drug(s)

References

1 Citrullinated histone H3, a biomarker for neutrophil extracellular trap formation, predicts the risk of mortality in patients with cancer.Br J Haematol. 2019 Jul;186(2):311-320. doi: 10.1111/bjh.15906. Epub 2019 Apr 9.
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