Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLQH0D6)

• DOT Name: Histone H2B type 1-C/E/F/G/I (H2BC10)
• Synonyms: Histone H2B.1 A; Histone H2B.a; H2B/a; Histone H2B.g; H2B/g; Histone H2B.h; H2B/h; Histone H2B.k; H2B/k; Histone H2B.l; H2B/l
• Gene Name: H2BC10
• Related Disease:
  Systemic lupus erythematosus
  Breast cancer
  Breast carcinoma
  Breast neoplasm
• UniProt ID: H2B1C_HUMAN
• PDB ID: 5GT0 ; 5KGF ; 6ACO ; 6C0W ; 6FML ; 6R0C ; 6RNY ; 6SE0 ; 6SE6 ; 6SEE ; 6SEF ; 6SEG ; 6UPK ; 6UPL ; 6X59 ; 6X5A ; 6XJD ; 7A08 ; 7JO9 ; 7JOA ; 7PII ; 7R5R ; 7TAN ; 7TRF ; 7U46 ; 7U47 ; 7U4D ; 7U50 ; 7U51 ; 7U52 ; 7U53 ; 7UV9 ; 7Y8R ; 7YWX ; 7YYH ; 8ATF ; 8AV6 ; 8OFF ; 8OO7 ; 8OOA ; 8OOP ; 8OOS ; 8OX0 ; 8OX1
• Pfam ID: PF00125
• Sequence:
  MPEPAKSAPAPKKGSKKAVTKAQKKDGKKRKRSRKESYSVYVYKVLKQVHPDTGISSKAM
  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.; Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.
• 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]

31 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[15]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[16]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[17]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[19]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[21]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[22]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[10]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[12]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[29]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid decreases the expression of Histone H2B type 1-C/E/F/G/I (H2BC10).	[31]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Histone H2B type 1-C/E/F/G/I (H2BC10).	[24]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Histone H2B type 1-C/E/F/G/I (H2BC10).	[30]

References

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• [21] Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1. J Surg Res. 2007 Apr;138(2):163-9. doi: 10.1016/j.jss.2006.05.037. Epub 2007 Jan 25.
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• [23] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
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