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FLASH GENE
Symbol HDAC2 contributors: mct/shn - updated : 06-11-2014
HGNC name histone deacetylase 2
HGNC id 4853
Location 6q21      Physical location : 114.257.321 - 114.292.359
Synonym name
  • YY1-associated factor 1
  • transcriptional regulator homolog RPD3
  • Synonym symbol(s) RPD3, YAF1, HD2
    EC.number 3.5.1.98
    DNA
    TYPE functioning gene
    STRUCTURE 35.04 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D6S1603 - D6S261 - HDAC2 - D6S401 - D6S454 - qter
    Physical map
    FYN 6q21 FYN oncogene related to SRC, FGR, YES WISP3 6q22-q23 WNT1 inducible signaling pathway protein 3 TUBE1 6q12 tubulin, epsilon 1 LAMA4 6q21 laminin, alpha 4 LOC345882 6q22.1 similar to Pin2-interacting protein X1 (TRF1-interacting protein 1) (Liver-related putative tumor suppressor) (67-11-3 protein) LOC221278 6q22.1 similar to ret finger protein-like 1 LOC391960 6 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) LOC345884 6q22.1 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC391961 6 similar to fem-1 homolog a (C.elegans) LOC389424 6 similar to Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog) (hG4-1) LOC391962 6 similar to Cytokine inducible SH2-containing protein 5 (Suppressor of cytokine signaling 5) (SOCS-5) (Cytokine-inducible SH2 protein 6) (CIS-6) LOC389425 6 similar to ribosomal protein S27a LOC221286 6q22.1 similar to ribosomal protein L30 MARCKS 6q21-q22.2 myristoylated alanine-rich protein kinase C substrate FLJ34503 6q22.2 hypothetical protein FLJ34503 HDAC2 6q21 histone deacetylase 2 HS3ST5 6q22.31 heparan sulfate (glucosamine) 3-O-sulfotransferase 5 LOC391963 6 similar to DnaJ homolog subfamily A member 1 (Heat shock 40 kDa protein 4) (DnaJ protein homolog 2) (HSJ-2) (HSDJ) FRK 6q21-q22.3 fyn-related kinase NT5C2L1 6q22.31 5'-nucleotidase, cytosolic II-like 1 COL10A1 6q21-q22.3 collagen, type X, alpha 1(Schmid metaphyseal chondrodysplasia) TSPYL4 6q22.31 TSPY-like 4 RPS5P1 6q22.1-q22.3 ribosomal protein S5 pseudogene 1 TSPYL 6q21-q23 TSPY-like
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 6656 55 488 - 2002 12176973
    also called variant 1
    15 splicing 6684 - - - 2002 12176973
  • non-coding RNA
  • also called variant 2
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     pharynx   highly
    Hearing/Equilibriumear   highly
    Nervousbrain   lowly
    Respiratorylung   lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    mono polymer complex
    HOMOLOGY
    interspecies homolog to Hdac2, Rattus norvegicus
    ortholog to Hdac2, Mus musculus
    intraspecies homolog to HDAC1
    Homologene
    FAMILY
  • histone deacetylase family, type I subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    basic FUNCTION
  • responsible for the deacetylation of lysine residues on the N-terminal part of the core histones
  • controls myocardial growth, morphogenesis, and contractility
  • having a key role in mediating corticosteroid-regulated gene expression
  • plays an important role in transcription regulation, cell cycle progression and developmental events
  • important for glucocorticoid-induced transrepression of the POMC gene in the negative feedback regulation mechanism
  • functioning in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory
  • plays an important role in cell proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts
  • regulates chromatin plasticity and enhances DNA vulnerability
  • deacetylates class II transactivator and suppresses its activity in macrophages and smooth muscle cells
  • controls neuronal development and required for neuronal specification
  • directly deacetylates KLF4
  • chromatin-associated protein, effector of SUMO-dependent changes in chromatin structure and gene expression
  • not implicated in the control of embryonic stem cell differentiation
  • regulate unique and overlapping sets of genes in human erythroid progenitor cells
  • regulates p53-p21(Cip)-independent pathways critical for maintaining cell cycle progression
  • having sumoylation-promoting activity and regulating cap-dependent mRNA translation
  • transcription repressor, present in the translation initiation complex and induces EIF4E sumoylation in a deacetylase-independent manner
  • possesses deacetylase-independent SUMO E3 ligase-like activity and activates protein synthesis of a subset of genes related to proliferation and apoptosis
  • regulates gene expression at both transcriptional and translational levels
  • HDAC1 and HDAC2 promote proper DNA double-strand break signaling and repair, predominantly through their requirement for effective NHEJ (nonhomologous end-joining)
  • HDAC1 and HDAC2 participate in the DNA-damage response through their recruitment to DNA damage (MID: 20802485)
  • critical for myelination of the peripheral nervous system (
  • activates the transcriptional program of myelination in synergy with Sox10
  • HDAC1 and HDAC2 contribute differently to the development of specific hematopoietic lineages
  • CELLULAR PROCESS cell cycle, progression
    nucleotide, chromatin organization
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • forming transcriptional repressor complexes
  • part of a histone deacetylase complex containing HDAC1, AOF2, RCOR1, ZNF261, ZNF198, KIAA0182 and GTF2I
  • HDAC1 and HDAC2 interact together to form the catalytic core of a number of higher-order complexes including SIN3A, RCOR1
  • role in cell cycle regulation and haematopoiesis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • breast cancer 1, early onset, BRCA1
  • ataxia telangiectasia and Rad3 related, ATR and chromodomain helicase DNA binding protein 4, CHD4
  • embryonic ectoderm development, EED
  • SKI interacting protei, SKIP
  • DNA (cytosine-5-)-methyltransferase 1, DNMT1
  • BCL6 corepressor, BCoR
  • nuclear receptor corepressor 2, NCOR2
  • DNA topoisomerase II beta, TOP2B
  • REST corepressor 1, RCOR1
  • promyelocytic leukemia, PML
  • silencing mediator of retinoic acid and thyroid hormone receptor, SMRT
  • YY1 transcription factor, YY1
  • FK506 binding protein 3, 25kDa, FKBP25
  • v-rel reticuloendotheliosis viral oncogene homolog A (avian), RELA
  • hairless homolog (mouse), HR
  • histone deacetylase 10, HDAC10
  • suppressor of variegation 3-9 homolog 1 (Drosophila), SUV39H1
  • sal-like 1 (Drosophila), SALL1
  • NF-kappa B p65
  • Sp1 and Sp3 transcription factor
  • EP300 interacting inhibitor of differentiation 2, EID2
  • . Epstein-Barr virus (EBV) nuclear antigen 3C, EBNA3C
  • ErbB-3 binding protein 1, EBP1
  • chromodomain helicase DNA binding protein 1, CHD1
  • metastasis associated 1, MTA1
  • APEX nuclease (multifunctional DNA repair enzyme) 1, APE1
  • DNA (cytosine-5-)-methyltransferase 3 beta, DNMT3B
  • PHD finger protein 21A, PHF21A
  • sucrose nonfermenting protein 2 homolog, SNF2h
  • EP300 interacting inhibitor of differentiation 3, EID3
  • regulatory factor X, 5 (influences HLA class II expression), RFX5
  • directly deacetylated KLF4
  • histone deacetylase (HDAC2) and PADI4 interact with TP53 through CDKN1A promoter to regulate gene expression
  • interacting with NFE2L2 (reduced HDAC2 activity in chronic obstructive pulmonary disease may account for increased NFE2L2 acetylation, reduced NFE2L2 stability and impaired anti oxidant defences)
  • HDAC3-RAC1 interaction, but not HDAC3 activity, is necessary for down-regulation of HDAC2 by RAC1
  • HDAC2 may act as a negative regulator of CCL2
  • HDAC2, negatively regulated by MS4A2 and HDAC3, is under the control of proteasome-dependent ubiquitination
  • novel role of HDAC2 as a regulator of SLC6A4 gene expression in intestinal epithelial cells
  • HLCS acts as a biotin-independent transcriptional repressor interacting with HDAC1, HDAC2 and HDAC7
  • HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, thus facilitating the functionality of complex formation to repress cell proliferation
  • SIN3A-associated HDAC1/2-activity is essential for hematopoietic stem cell homeostasis
  • HDAC2 is a critical regulator of ARG2 expression and thereby endothelial nitric oxide and endothelial function
  • cell & other
    REGULATION
    inhibited by Nitration of distinct tyrosine residues
  • sphingosine-1-phosphate, S1P
  • orkhead box P3, FOXP3
    Other S-nitrosylated
    regulated by all-trans retinoic acid (induces HDAC2 phosphorylation, which in turn leads to the dissociation of HDAC2 from KLF4 complexes, and prevents KLF4 deacetylation by HDAC2)
    phosphorylated uniquely by protein kinase CK2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in colon, gastric and endometrial tumor
    constitutional       gain of function
    specifically up-regulated in dystrophic muscles
    constitutional     --low  
    in end-stage dilated cardiomyopathy
    constitutional        
    altered expression and/or subcellular localization in Cushing Disease
    constitutional        
    down-regulated in airway epithelial cells lacking CFTR in the cystic fibrosis
    tumoral     --over  
    in diffuse large B cell lymphoma
    tumoral        
    highly expressed in renal cancer cell
    tumoral       loss of function
    inactivating mutation leads to dysregulation of apoptosis in microsatellite instability tumors
    tumoral     --over  
    highly expressed in undifferentiated, aggressive teratocarcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • biomarker for malignant teratomas
  • Therapy target
    SystemTypeDisorderPubmed
    neuromuscularspinal muscular atrophy 
    with HDAC6 may be the most compelling targets for SMA therapy (HDAC2 deficiency resulted in increased synapse number as well as improved memory formation)
    tumor  
    inhibitors of histone deacetylase in tumors with HDAC2 mutations
    neuromuscularmyopathy 
    pharmacological modulation of HDAC2 could also be exploited to modulate the effect of glucocorticoids in the current treatment of DMD
    bloodhemoglobin 
    potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease
    respiratorylungchr.Bronchopathy obstructive
    potential target for devising better therapies for patients who are refractory/insensitive to steroid treatments, such as patients with COPD, asthma
    immunologyautoimmunearticular
    potential target for devising better therapies for patients who are refractory/insensitive to steroid treatments, such as patients with rheumatoid arthritis
    immunologyautoimmunedigestive
    potential target for devising better therapies for patients who are refractory/insensitive to steroid treatments, such as patients with inflammatory bowel disease
    cardiovascularatheroma 
    overexpression or activation of HDAC2 represents a novel therapy for endothelial dysfunction and atherosclerosis
    ANIMAL & CELL MODELS
  • mice lacking HDAC2 survive until the perinatal period, when they succumb to a spectrum of cardiac defects with obliteration of the lumen of the right ventricle, excessive hyperplasia and apoptosis of cardiomyocytes, and bradycardia
  • Cardiac-specific deletion of HDAC1 and HDAC2 genes results in neonatal lethality with cardiac arrhythmias, dilated cardiomyopathy, and up-regulation of genes encoding skeletal muscle-specific contractile proteins and calcium channels
  • deletion of both HDAC1 and HDAC2 genes in mouse developing neurons results in severe hippocampal abnormalities, absence of cerebellar foliation, disorganization of cortical neurons, and lethality by postnatal day 7
  • loss of HDAC2 in NFe2l2 deficient mice is a crucial component of increased susceptibility to oxidative stress-induced inflammatory response in the lungs
  • ablation of Hdac1 and Hdac2 specifically in mouse Schwann cells, result in massive Schwann cell loss and virtual absence of myelin in mutant sciatic nerves (