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FLASH GENE

Symbol

HDAC2

contributors: mct/shn - updated : 06-11-2017

HGNC name	histone deacetylase 2
HGNC id	4853

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001527 14 - 6656 NP_001518 55 488 - 2002 12176973 also called variant 1 NR_033441 15 splicing 6684 - - - 2002 12176973 non-coding RNA also called variant 2

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   pharynx       highly Hearing/Equilibrium ear       highly Nervous brain       lowly Respiratory lung       lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed neuromuscular spinal 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 neuromuscular myopathy   pharmacological modulation of HDAC2 could also be exploited to modulate the effect of glucocorticoids in the current treatment of DMD blood hemoglobin   potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease respiratory lung chr.Bronchopathy obstructive potential target for devising better therapies for patients who are refractory/insensitive to steroid treatments, such as patients with COPD, asthma immunology autoimmune articular potential target for devising better therapies for patients who are refractory/insensitive to steroid treatments, such as patients with rheumatoid arthritis immunology autoimmune digestive potential target for devising better therapies for patients who are refractory/insensitive to steroid treatments, such as patients with inflammatory bowel disease cardiovascular atheroma   overexpression or activation of HDAC2 represents a novel therapy for endothelial dysfunction and atherosclerosis cancer muscle   In synovial sarcoma, HDAC2 inactivation demonstrates significant therapeutic effect by degradation of the SS18-SSX driver oncoprotein

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 (