Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9XHQ3C)

• DOT Name: Histone H3.3 (H3-3B)
• Gene Name: H3-3B
• Related Disease:
  Bryant-Li-Bhoj neurodevelopmental syndrome 1
  Central nervous system neoplasm
  Adult glioblastoma
  Alpha thalassemia-X-linked intellectual disability syndrome
  Anaplastic astrocytoma
  Astrocytoma
  Bone giant cell tumor
  Bone sarcoma
  Brain neoplasm
  Carcinoma
  Chromosomal disorder
  Glioma
  Gliosarcoma
  Hepatocellular carcinoma
  Medulloblastoma
  Neoplasm
  Neuroepithelial neoplasm
  Osteoarthritis
  Osteosarcoma
  Schizophrenia
  Undifferentiated carcinoma
  Advanced cancer
  Epithelial ovarian cancer
  Colorectal carcinoma
  Ductal breast carcinoma in situ
  Malignant glioma
  Metastatic malignant neoplasm
• UniProt ID: H33_HUMAN
• PDB ID: 2L43 ; 3ASK ; 3ASL ; 3AV2 ; 3JVK ; 3MUK ; 3MUL ; 3QL9 ; 3QLA ; 3QLC ; 3WTP ; 4GNE ; 4GNF ; 4GNG ; 4GU0 ; 4GUR ; 4GUS ; 4GY5 ; 4H9N ; 4H9O ; 4H9P ; 4H9Q ; 4H9R ; 4H9S ; 4HGA ; 4L58 ; 4N4I ; 4O62 ; 4QQ4 ; 4TMP ; 4U7T ; 4W5A ; 5B32 ; 5B33 ; 5BNV ; 5BNX ; 5DWQ ; 5DX0 ; 5JA4 ; 5JJY ; 5JLB ; 5KDM ; 5X7X ; 6A5L ; 6A5O ; 6A5P ; 6A5R ; 6A5T ; 6A5U ; 6HGT ; 6INQ ; 6IR9 ; 6J4W ; 6J4X ; 6J4Y ; 6J4Z ; 6J50 ; 6J51 ; 6J9J ; 6PZV ; 6QXZ ; 6R0C ; 6RNY ; 6U04 ; 7A08 ; 7CIZ ; 7CJ0 ; 7CWH ; 7OKP ; 7V1L ; 7V1M ; 7VCQ ; 7W5M ; 7WBV ; 7WBW ; 7WBX ; 7XSE ; 7XSX ; 7XSZ ; 7XT7 ; 7XTD ; 7XTI ; 8JH2 ; 8JH3 ; 8JH4
• Pfam ID: PF00125
• Sequence:
  MARTKQTARKSTGGKAPRKQLATKAARKSAPSTGGVKKPHRYRPGTVALREIRRYQKSTE
  LLIRKLPFQRLVREIAQDFKTDLRFQSAAIGALQEASEAYLVGLFEDTNLCAIHAKRVTI
  MPKDIQLARRIRGERA
• Function: Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. 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:
  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)
  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)
  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)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bryant-Li-Bhoj neurodevelopmental syndrome 1	DISXQDDJ	Definitive	Autosomal dominant	[1]
Central nervous system neoplasm	DISFC18W	Definitive	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Strong	Genetic Variation	[3]
Alpha thalassemia-X-linked intellectual disability syndrome	DISV7OEV	Strong	Genetic Variation	[4]
Anaplastic astrocytoma	DISSBE0K	Strong	Genetic Variation	[5]
Astrocytoma	DISL3V18	Strong	Altered Expression	[6]
Bone giant cell tumor	DIS0RGK9	Strong	Genetic Variation	[7]
Bone sarcoma	DIS95A0A	Strong	Biomarker	[8]
Brain neoplasm	DISY3EKS	Strong	Genetic Variation	[9]
Carcinoma	DISH9F1N	Strong	Biomarker	[10]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[11]
Glioma	DIS5RPEH	Strong	Genetic Variation	[12]
Gliosarcoma	DIS985MG	Strong	Genetic Variation	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Medulloblastoma	DISZD2ZL	Strong	Genetic Variation	[15]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[16]
Neuroepithelial neoplasm	DISCYKLP	Strong	Genetic Variation	[17]
Osteoarthritis	DIS05URM	Strong	Biomarker	[18]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[19]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[20]
Undifferentiated carcinoma	DISIAZST	Strong	Biomarker	[10]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[21]
Epithelial ovarian cancer	DIS56MH2	moderate	Genetic Variation	[22]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[23]
Ductal breast carcinoma in situ	DISLCJY7	Limited	Genetic Variation	[24]
Malignant glioma	DISFXKOV	Limited	Genetic Variation	[25]
Metastatic malignant neoplasm	DIS86UK6	Limited	Genetic Variation	[25]

2 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 H3.3 (H3-3B).	[26]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Histone H3.3 (H3-3B).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Histone H3.3 (H3-3B).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H3.3 (H3-3B).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone H3.3 (H3-3B).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H3.3 (H3-3B).	[30]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone H3.3 (H3-3B).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone H3.3 (H3-3B).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Histone H3.3 (H3-3B).	[34]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Histone H3.3 (H3-3B).	[35]
Marinol	DM70IK5	Approved	Marinol increases the expression of Histone H3.3 (H3-3B).	[36]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Histone H3.3 (H3-3B).	[37]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Histone H3.3 (H3-3B).	[38]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H3.3 (H3-3B).	[39]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Histone H3.3 (H3-3B).	[40]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Histone H3.3 (H3-3B).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Histone H3.3 (H3-3B).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone H3.3 (H3-3B).	[42]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Histone H3.3 (H3-3B).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H3.3 (H3-3B).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone H3.3 (H3-3B).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H3.3 (H3-3B).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone H3.3 (H3-3B).	[47]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Histone H3.3 (H3-3B).	[48]

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