Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0FDCUC)

• DOT Name: Histone H2B type 2-E (H2BC21)
• Synonyms: H2B-clustered histone 21; Histone H2B-GL105; Histone H2B.q; H2B/q
• Gene Name: H2BC21
• Related Disease:
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Epithelial ovarian cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: H2B2E_HUMAN
• PDB ID: 4NFT; 6A7U; 6KBB; 6M4D; 6M4G; 6M4H; 7BXT; 7EA8; 7U0G; 7U0I; 7U0J; 8DK5; 8EVG; 8EVH; 8EVI; 8EVJ; 8H1T; 8SPS; 8SPU; 8SYP
• Pfam ID: PF00125
• Sequence:
  MPEPAKSAPAPKKGSKKAVTKAQKKDGKKRKRSRKESYSIYVYKVLKQVHPDTGISSKAM
  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)
  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

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[1]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[2]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[1]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[1]

1 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 H2B type 2-E (H2BC21).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Histone H2B type 2-E (H2BC21).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Histone H2B type 2-E (H2BC21).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H2B type 2-E (H2BC21).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone H2B type 2-E (H2BC21).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2B type 2-E (H2BC21).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histone H2B type 2-E (H2BC21).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Histone H2B type 2-E (H2BC21).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Histone H2B type 2-E (H2BC21).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Histone H2B type 2-E (H2BC21).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Histone H2B type 2-E (H2BC21).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Histone H2B type 2-E (H2BC21).	[15]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Histone H2B type 2-E (H2BC21).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Histone H2B type 2-E (H2BC21).	[17]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Histone H2B type 2-E (H2BC21).	[18]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Histone H2B type 2-E (H2BC21).	[19]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Histone H2B type 2-E (H2BC21).	[20]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Histone H2B type 2-E (H2BC21).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Histone H2B type 2-E (H2BC21).	[22]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Histone H2B type 2-E (H2BC21).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Histone H2B type 2-E (H2BC21).	[10]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Histone H2B type 2-E (H2BC21).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Histone H2B type 2-E (H2BC21).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone H2B type 2-E (H2BC21).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Histone H2B type 2-E (H2BC21).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H2B type 2-E (H2BC21).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone H2B type 2-E (H2BC21).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H2B type 2-E (H2BC21).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone H2B type 2-E (H2BC21).	[29]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone H2B type 2-E (H2BC21).	[30]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Histone H2B type 2-E (H2BC21).	[31]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Histone H2B type 2-E (H2BC21).	[32]

References

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