Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMFQ662)

• DOT Name: Histone H2A type 1-B/E (H2AC4)
• Synonyms: Histone H2A.2; Histone H2A/a; Histone H2A/m
• Gene Name: H2AC4
• Related Disease:
  Gout
  Acute myelogenous leukaemia
• UniProt ID: H2A1B_HUMAN
• PDB ID: 2CV5 ; 2RVQ ; 3A6N ; 3AFA ; 3AN2 ; 3AV1 ; 3AV2 ; 3AYW ; 3AZE ; 3AZF ; 3AZG ; 3AZH ; 3AZI ; 3AZJ ; 3AZK ; 3AZL ; 3AZM ; 3AZN ; 3W96 ; 3W97 ; 3W98 ; 3W99 ; 3WKJ ; 3WTP ; 3X1S ; 3X1V ; 4YM5 ; 4YM6 ; 4Z5T ; 5AV5 ; 5AV6 ; 5AV8 ; 5AV9 ; 5AVB ; 5AVC ; 5AY8 ; 5B0Y ; 5B0Z ; 5B24 ; 5B2I ; 5B2J ; 5B31 ; 5B32 ; 5B40 ; 5CPI ; 5CPJ ; 5CPK ; 5GSE ; 5GTC ; 5GXQ ; 5JRG ; 5X7X ; 5XF3 ; 5XF4 ; 5XF5 ; 5Y0C ; 5Y0D ; 5Z23 ; 5ZBX ; 6A5L ; 6A5O ; 6A5P ; 6A5R ; 6A5T ; 6A5U ; 6ACL ; 6AEE ; 6BUZ ; 6E0C ; 6E0P ; 6HKT ; 6HTS ; 6INQ ; 6IPU ; 6IQ4 ; 6IR9 ; 6J4W ; 6J4X ; 6J4Y ; 6J4Z ; 6J50 ; 6J51 ; 6JR0 ; 6JR1 ; 6JXD ; 6KE9 ; 6KXV ; 6L49 ; 6L4A ; 6L9H ; 6L9Z ; 6LA2 ; 6LA8 ; 6LA9 ; 6LAB ; 6LE9 ; 6LER ; 6M3V ; 6M44 ; 6O1D ; 6R8Y ; 6R8Z ; 6R90 ; 6R91 ; 6R92 ; 6R93 ; 6R94 ; 6T79 ; 6T7A ; 6T7B ; 6T7C ; 6T7D ; 6T90 ; 6T93 ; 6USJ ; 6V2K ; 6V92 ; 6YOV ; 7BWD ; 7BXT ; 7BY0 ; 7C0M ; 7CCQ ; 7CCR ; 7COW ; 7D1Z ; 7D20 ; 7DBP ; 7K5X ; 7K5Y ; 7K60 ; 7K61 ; 7K63 ; 7LYA ; 7LYB ; 7LYC ; 7NL0 ; 7PET ; 7PEU ; 7PEV ; 7PEW ; 7PEX ; 7PEY ; 7PEZ ; 7PF0 ; 7PF2 ; 7PF3 ; 7PF4 ; 7PF5 ; 7PF6 ; 7PFA ; 7PFC ; 7PFD ; 7PFE ; 7PFF ; 7PFT ; 7PFU ; 7PFV ; 7PFW ; 7PFX ; 7SCY ; 7SCZ ; 7V90 ; 7V96 ; 7V99 ; 7V9C ; 7V9J ; 7V9K ; 7V9S ; 7VA4 ; 7VCL ; 7VZ4 ; 7W9V ; 7WBV ; 7WBW ; 7WBX ; 7XCR ; 7XCT ; 7XD0 ; 7XD1 ; 7XSE ; 7XSX ; 7XSZ ; 7XT7 ; 7XTD ; 7XTI ; 7XVL ; 7XVM ; 7XX5 ; 7XX6 ; 7XX7 ; 7XZX ; 7XZY ; 7XZZ ; 7Y00 ; 7Y7I ; 7ZI4 ; 8G57 ; 8GRM ; 8H0V ; 8H0W ; 8HAG ; 8HAH ; 8HAI ; 8HAJ ; 8HAK ; 8HAL ; 8HAM ; 8HAN ; 8HE5 ; 8HQY ; 8HR1 ; 8I17 ; 8IEG ; 8IEJ ; 8JH2 ; 8JH3 ; 8JH4 ; 8JHG ; 8JL9 ; 8JLA ; 8JLB ; 8JLD ; 8KB5 ; 8OSJ ; 8OSK ; 8OSL ; 8OTS ; 8OTT
• Pfam ID: PF00125 ; PF16211
• Sequence:
  MSGRGKQGGKARAKAKTRSSRAGLQFPVGRVHRLLRKGNYSERVGAGAPVYLAAVLEYLT
  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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gout	DISHC0U7	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[2]

27 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 H2A type 1-B/E (H2AC4).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone H2A type 1-B/E (H2AC4).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H2A type 1-B/E (H2AC4).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone H2A type 1-B/E (H2AC4).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H2A type 1-B/E (H2AC4).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H2A type 1-B/E (H2AC4).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone H2A type 1-B/E (H2AC4).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Histone H2A type 1-B/E (H2AC4).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone H2A type 1-B/E (H2AC4).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Histone H2A type 1-B/E (H2AC4).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Histone H2A type 1-B/E (H2AC4).	[13]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Histone H2A type 1-B/E (H2AC4).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Histone H2A type 1-B/E (H2AC4).	[15]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Histone H2A type 1-B/E (H2AC4).	[16]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Histone H2A type 1-B/E (H2AC4).	[17]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H2A type 1-B/E (H2AC4).	[18]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Histone H2A type 1-B/E (H2AC4).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Histone H2A type 1-B/E (H2AC4).	[20]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Histone H2A type 1-B/E (H2AC4).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Histone H2A type 1-B/E (H2AC4).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone H2A type 1-B/E (H2AC4).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H2A type 1-B/E (H2AC4).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H2A type 1-B/E (H2AC4).	[25]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone H2A type 1-B/E (H2AC4).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone H2A type 1-B/E (H2AC4).	[27]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Histone H2A type 1-B/E (H2AC4).	[28]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Histone H2A type 1-B/E (H2AC4).	[29]

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-B/E (H2AC4).	[10]

References

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