Details of Drug Off-Target (DOT)

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

• DOT Name: Histone deacetylase 2 (HDAC2)
• Synonyms: HD2; EC 3.5.1.98; Protein deacylase HDAC2; EC 3.5.1.-
• Gene Name: HDAC2
• UniProt ID: HDAC2_HUMAN
• PDB ID: 3MAX ; 4LXZ ; 4LY1 ; 5IWG ; 5IX0 ; 6G3O ; 6WBW ; 6WBZ ; 6WHN ; 6WHO ; 6WHQ ; 6WHZ ; 6WI3 ; 6XDM ; 6XEB ; 6XEC ; 7JS8 ; 7KBG ; 7KBH ; 7LTG ; 7LTK ; 7LTL ; 7MOS ; 7MOT ; 7MOX ; 7MOY ; 7MOZ ; 7ZZO ; 7ZZP ; 7ZZR ; 7ZZS ; 7ZZT ; 7ZZU ; 7ZZW ; 8A0B ; 8BPA ; 8BPB ; 8BPC ; 8C60
• EC Number: 3.5.1.-; 3.5.1.98
• Pfam ID: PF00850
• Sequence:
  MAYSQGGGKKKVCYYYDGDIGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKA
  TAEEMTKYHSDEYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVA
  GAVKLNRQQTDMAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHH
  GDGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNFPMRDGIDDESYGQ
  IFKPIISKVMEMYQPSAVVLQCGADSLSGDRLGCFNLTVKGHAKCVEVVKTFNLPLLMLG
  GGGYTIRNVARCWTYETAVALDCEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTPEYM
  EKIKQRLFENLRMLPHAPGVQMQAIPEDAVHEDSGDEDGEDPDKRISIRASDKRIACDEE
  FSDSEDEGEGGRRNVADHKKGAKKARIEEDKKETEDKKTDVKEEDKSKDNSGEKTDTKGT
  KSEQLSNP
• Function: Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2. Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively.
• Tissue Specificity: Widely expressed; lower levels in brain and lung.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Polycomb repressive complex (hsa03083)
  Cell cycle (hsa04110)
  Longevity regulating pathway - multiple species (hsa04213)
  Notch sig.ling pathway (hsa04330)
  TGF-beta sig.ling pathway (hsa04350)
  Neutrophil extracellular trap formation (hsa04613)
  Thyroid hormone sig.ling pathway (hsa04919)
  Huntington disease (hsa05016)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
  Human papillomavirus infection (hsa05165)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Viral carcinogenesis (hsa05203)
  MicroR.s in cancer (hsa05206)
  Chronic myeloid leukemia (hsa05220)
• Reactome Pathway:
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  HDACs deacetylate histones (R-HSA-3214815)
  Notch-HLH transcription pathway (R-HSA-350054)
  ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression (R-HSA-427389)
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  Regulation of TP53 Activity through Acetylation (R-HSA-6804758)
  RNA Polymerase I Transcription Initiation (R-HSA-73762)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Regulation of MECP2 expression and activity (R-HSA-9022692)
  MECP2 regulates neuronal receptors and channels (R-HSA-9022699)
  FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes (R-HSA-9615017)
  EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)
  Potential therapeutics for SARS (R-HSA-9679191)
  STAT3 nuclear events downstream of ALK signaling (R-HSA-9701898)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  p75NTR negatively regulates cell cycle via SC1 (R-HSA-193670)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Histone deacetylase 2 (HDAC2) increases the response to substance of Fluorouracil.	[29]
Scopolamine	DMOM8AL	Approved	Histone deacetylase 2 (HDAC2) increases the Memory impairment ADR of Scopolamine.	[30]

24 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 deacetylase 2 (HDAC2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone deacetylase 2 (HDAC2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone deacetylase 2 (HDAC2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Histone deacetylase 2 (HDAC2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone deacetylase 2 (HDAC2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the activity of Histone deacetylase 2 (HDAC2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Histone deacetylase 2 (HDAC2).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Histone deacetylase 2 (HDAC2).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Histone deacetylase 2 (HDAC2).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Histone deacetylase 2 (HDAC2).	[11]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Histone deacetylase 2 (HDAC2).	[12]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Histone deacetylase 2 (HDAC2).	[13]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Histone deacetylase 2 (HDAC2).	[14]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone deacetylase 2 (HDAC2).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Histone deacetylase 2 (HDAC2).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Histone deacetylase 2 (HDAC2).	[18]
MGCD-0103	DM726HX	Phase 2	MGCD-0103 decreases the expression of Histone deacetylase 2 (HDAC2).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Histone deacetylase 2 (HDAC2).	[20]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Histone deacetylase 2 (HDAC2).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone deacetylase 2 (HDAC2).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the activity of Histone deacetylase 2 (HDAC2).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Histone deacetylase 2 (HDAC2).	[18]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of Histone deacetylase 2 (HDAC2).	[27]
Oxalic Acid	DMLN2GQ	Investigative	Oxalic Acid increases the expression of Histone deacetylase 2 (HDAC2).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the methylation of Histone deacetylase 2 (HDAC2).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Histone deacetylase 2 (HDAC2).	[21]
MG-132	DMKA2YS	Preclinical	MG-132 increases the ubiquitination of Histone deacetylase 2 (HDAC2).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Histone deacetylase 2 (HDAC2).	[25]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the metabolism of Histone deacetylase 2 (HDAC2).	[16]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
acrolein	DMAMCSR	Investigative	acrolein affects the binding of Histone deacetylase 2 (HDAC2).	[26]

References

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