Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF3YK7V)

• DOT Name: Histone H2A type 1-C (H2AC6)
• Synonyms: H2A-clustered histone 6; Histone H2A/l
• Gene Name: H2AC6
• Related Disease:
  Gout
  Narcolepsy
  Schizophrenia
  Lung carcinoma
  Lung squamous cell carcinoma
• UniProt ID: H2A1C_HUMAN
• PDB ID: 6C0W; 6MUO; 6MUP; 6UPK; 6UPL; 7A08; 7PII; 7R5R; 7U46; 7U47; 7U4D; 7Y8R; 7YWX; 7YYH; 8OO7; 8OOA; 8OOP; 8OOS; 8OX0; 8OX1
• Pfam ID: PF00125 ; PF16211
• Sequence:
  MSGRGKQGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGNYAERVGAGAPVYLAAVLEYLT
  AEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGRVTIAQGGVLPNIQAVLLPKK
  TESHHKAKGK
• 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:
  ATP-dependent chromatin remodeling (hsa03082)
  Necroptosis (hsa04217)
  Neutrophil extracellular trap formation (hsa04613)
  Alcoholism (hsa05034)
  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)
  RMTs methylate histone arginines (R-HSA-3214858)
  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)
  UCH proteinases (R-HSA-5689603)
  Ub-specific processing proteases (R-HSA-5689880)
  Metalloprotease DUBs (R-HSA-5689901)
  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)
  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)
  Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gout	DISHC0U7	Strong	Genetic Variation	[1]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[4]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[4]

31 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 H2A type 1-C (H2AC6).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone H2A type 1-C (H2AC6).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H2A type 1-C (H2AC6).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone H2A type 1-C (H2AC6).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2A type 1-C (H2AC6).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H2A type 1-C (H2AC6).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histone H2A type 1-C (H2AC6).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histone H2A type 1-C (H2AC6).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Histone H2A type 1-C (H2AC6).	[14]
Marinol	DM70IK5	Approved	Marinol increases the expression of Histone H2A type 1-C (H2AC6).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Histone H2A type 1-C (H2AC6).	[16]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Histone H2A type 1-C (H2AC6).	[17]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Histone H2A type 1-C (H2AC6).	[18]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid decreases the expression of Histone H2A type 1-C (H2AC6).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone H2A type 1-C (H2AC6).	[20]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H2A type 1-C (H2AC6).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Histone H2A type 1-C (H2AC6).	[22]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Histone H2A type 1-C (H2AC6).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Histone H2A type 1-C (H2AC6).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone H2A type 1-C (H2AC6).	[24]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Histone H2A type 1-C (H2AC6).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Histone H2A type 1-C (H2AC6).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Histone H2A type 1-C (H2AC6).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H2A type 1-C (H2AC6).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone H2A type 1-C (H2AC6).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H2A type 1-C (H2AC6).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone H2A type 1-C (H2AC6).	[29]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Histone H2A type 1-C (H2AC6).	[30]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Histone H2A type 1-C (H2AC6).	[31]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Histone H2A type 1-C (H2AC6).	[32]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Histone H2A type 1-C (H2AC6).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Histone H2A type 1-C (H2AC6).	[12]

References

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