Gene Report

Basic Information

Approved Symbol	HDAC5
Approved Name	histone deacetylase 5
Symbol Alias	KIAA0600, NY-CO-9, FLJ90614
Location	17q21
Position	chr17:42200872-42201009 (-)
External Links	Entrez Gene: 10014 Ensembl: ENSG00000108840 UCSC: uc002iff.1 HGNC ID: 14068
No. of Studies (Positive/Negative)	3(3/0)
Type	Literature-origin

Positive relationships between HDAC5 and MDD (count: 3)

Name in Literature	Reference	Research Type	Relation Description
HDAC5	Iga, 2007	patients and normal controls	Levels of HDAC5 and CREB mRNA were significantly higher in d...... Levels of HDAC5 and CREB mRNA were significantly higher in drug-free depressive patients than those of controls More...
histone deacetylase 5	Hobara, 2010	patients and normal controls	In MDD, the expression of HDAC2 and -5 mRNA was increased in...... In MDD, the expression of HDAC2 and -5 mRNA was increased in a depressive state, but not in a remissive state, compared to controls. More...
HDAC5	Belzeaux, 2010	patients and normal controls	We also observed that variations in other mRNA expression we...... We also observed that variations in other mRNA expression were associated with treatment efficacy or clinical improvement (CREB1, HDAC5, HSPA2, HTR1B, HTR2A, and SLC6A4/5HTT). More...

Positive relationships between HDAC5 and other components at different levels (count: 0)

Positive relationship network of HDAC5 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between HDAC5 and MDD (count: 0)

Negative relationships between HDAC5 and other components at different levels (count: 0)

HDAC5 related SNPs in MK4MDD (count: 0)

HDAC5 related proteins in MK4MDD (count: 0)

HDAC5 related GO terms (count: 54)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006954	inflammatory response	biological process	TAS[12711221]
GO:0032869	cellular response to insulin stimulus	biological process	NAS[18184930]
GO:0030182	neuron differentiation	biological process	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0070932	histone H3 deacetylation	biological process	IEA
GO:0042113	B cell activation	biological process	TAS[12711221]
GO:0005829	cytosol	cellular component	IEA
GO:0006351	transcription, DNA-templated	biological process	IEA
GO:0046872	metal ion binding	molecular function	IEA
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity	biological process	IMP[19071119]
GO:0002076	osteoblast development	biological process	IEA
GO:0044212	transcription regulatory region DNA binding	molecular function	IDA[19351956]
GO:0005515	protein binding	molecular function	IPI[10869435\|10898795\|15161933\|15194749\|15923258\|16919237\|17872950\|19666599\|23752268\|24229708\|24413532]
GO:0001047	core promoter binding	molecular function	IDA[24413532]
GO:0006342	chromatin silencing	biological process	TAS[10869435]
GO:0001025	RNA polymerase III transcription factor binding	molecular function	IPI[23867755]
GO:0032041	NAD-dependent histone deacetylase activity (H3-K14 specific)	molecular function	IEA
GO:0040029	regulation of gene expression, epigenetic	biological process	IMP[24413532]
GO:0000118	histone deacetylase complex	cellular component	TAS[12711221]
GO:0033558	protein deacetylase activity	molecular function	IMP[23867755]
GO:0008134	transcription factor binding	molecular function	IPI[19071119\|20408817]
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IMP[19071119]
GO:0005080	protein kinase C binding	molecular function	IPI[20188095]
GO:0070491	repressing transcription factor binding	molecular function	IPI[12242305]
GO:0006476	protein deacetylation	biological process	IMP[23867755]
GO:0030183	B cell differentiation	biological process	TAS[12711221]
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IDA[16236793]; IMP[10983972\|19351956\|23867755]
GO:0016575	histone deacetylation	biological process	IDA[10869435]
GO:0016568	chromatin modification	biological process	TAS[12711221]
GO:0010832	negative regulation of myotube differentiation	biological process	IMP[10983972\|11081517]
GO:0007219	Notch signaling pathway	biological process	TAS
GO:0006325	chromatin organization	biological process	TAS[12711221]
GO:0042493	response to drug	biological process	IEA
GO:0007507	heart development	biological process	IEA
GO:0003682	chromatin binding	molecular function	IEA
GO:0006338	chromatin remodeling	biological process	TAS[10220385]
GO:0016604	nuclear body	cellular component	IEA
GO:0042826	histone deacetylase binding	molecular function	IPI[23867755]
GO:0005634	nucleus	cellular component	IDA[10869435\|11081517\|23867755]
GO:0014823	response to activity	biological process	IEA
GO:0045892	negative regulation of transcription, DNA-templated	biological process	TAS[12711221]
GO:0071222	cellular response to lipopolysaccharide	biological process	IEA
GO:0004407	histone deacetylase activity	molecular function	IDA[10869435]
GO:0010830	regulation of myotube differentiation	biological process	ISS
GO:0005737	cytoplasm	cellular component	IDA[10869435\|11081517]
GO:0045668	negative regulation of osteoblast differentiation	biological process	IEA
GO:0005654	nucleoplasm	cellular component	IDA; TAS
GO:2000615	regulation of histone H3-K9 acetylation	biological process	IMP[23867755]
GO:0003714	transcription corepressor activity	molecular function	IEA
GO:0048742	regulation of skeletal muscle fiber development	biological process	IEA
GO:0090051	negative regulation of cell migration involved in sprouting angiogenesis	biological process	IMP[19351956]
GO:0043393	regulation of protein binding	biological process	IMP[19071119]
GO:0005794	Golgi apparatus	cellular component	IDA
GO:0042220	response to cocaine	biological process	IEA
GO:0033555	multicellular organismal response to stress	biological process	IEA

HDAC5 related KEGG pathways (count: 0)

HDAC5 related BioCarta pathways (count: 4)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
CARM_ER_PATHWAY	carm er_pathway	CARM1 and Regulation of the Estrogen Receptor	Several forms of post-translational modification regulate pr...... Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known. The methylation activity of CARM1 modulates the activity of specific transcriptional regulators. CARM1 acts as a coactivator for the myogenic transcription factor Mef2c, and is necessary for normal muscle cell differentiation. The estrogen receptor is another transcription factor that uses CARM1 as one of several coactivators, acting synergistically with CBP through the Grip1 member of the p160 family of coactivators. The interaction of estrogen receptor with various ligand-dependent coactivators may produce the tissue selective response of some estrogen receptor ligands like tamoxifen. More...
HDAC_PATHWAY	hdac pathway	Control of skeletal myogenesis by HDAC and calcium/calmodulin-dependent kinase (CaMK)	The differentiation of muscle cells is transcriptionally reg...... The differentiation of muscle cells is transcriptionally regulated, in part by the myocyte enhancer factor-2, MEF2. During myogenesis MEF2 binds to MyoD and other basic helix-loop-helix factors to activate transcription of genes involved in muscle cell differentiation. Transcriptional activation by MEF2 is blocked by interaction with HDAC5 and other histone deacetylases. In undifferentiated myoblasts, HDAC5 is present in the nucleus where it binds to MEF2 to block activation of muscle genes. When activated by IGF-1 signaling, CaM kinase phosphorylates HDAC proteins, causing them to be exported from the nucleus, releasing the block on MEF2 transcriptional activation and allowing differentiation to proceed. Transcription cofactors also interact with MEF2 to contribute to gene regulation and myogenesis. The transcriptional regulator NFAT, for example, acts as a cofactor for MEF2 when calcium and calcineurin signaling activate it. There are four members of the Mef2 gene family, Mef2a-2d. Mef2a is expressed in brain, heart and skeletal muscle. Mef2c is involved in myogenesis in cardiac and skeletal muscle. Mef2d is widely expressed, and may be involved in the regulation of T cell function as well as muscle. Several factors regulate Mef2 transcription factors, including Map kinases and histone deacetylase (HDAC) enzymes. Mef2 is phosphorylated by p38 map kinase, and phosphorylation of Mef2c by p38 contributes to skeletal muscle differentiation. BMK-1 (also called Erk5) is another member of the Map kinase family that regulates the activity of Mef2 family members and is unique in that it appears itself to possess a transcriptional activation domain and act as a transcriptional coactivator. Mekk3 disruption prevented normal cardiovascular development in mice and appears to signal through p38 and Mef2c in normal cardiovascular development. More...
PGC1A_PATHWAY	pgc1a pathway	Regulation of PGC-1a	Peroxisome proliferator-activated receptor gamma coactivator...... Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a tissue-specific coactivator that enhances the activity of many nuclear receptors and coordinates transcriptional programs important for energy metabolism and energy homeostasis. Inappropriate increases in PGC-1a activity have been linked to a number of pathological conditions including heart failure and diabetes. PGC-1a is highly expressed in metabolically active tissues including brown fat, skeletal muscle and heart. PGC-1a has been implicated in mitochondrial biogenesis in the heart and increased mitochondrial respiration in brown fat. PGC-1a is a coactivator for many factors including, CBP, Scr-1, PPARa, GR (glucocorticoid receptor), THR (thyroid hormone receptor), several orphan receptors and MEF2. This pathway illustrates two of the cofactor regulatory factors MEF2 and PPARa) and an example orphan receptor feedback inhibition loop. Glut4 is used as an example of the downstream elements leading to changes in metabolism. Ichida et al discovered the ERRa repression of PGC-1a. Their results suggest a novel mechanism of transcriptional control wherein ERR-a can function as a specific molecular repressor of PGC-1a. This suggests that other co-activators might also have specific repressors, adding another layer of combinatorial complexity in transcriptional regulation. Czubryt et al identified PGC-1 a as a key target of the MEF2/HDAC regulatory pathway and demonstrated this pathway's importance in maintenance of cardiac mitochondrial function. The linking of MEF2/HDAC provides an potential explanation for the increase in mitochondrial number observed in response to CaMK signaling. More...
ETS_PATHWAY	ets pathway	METS affect on Macrophage Differentiation	Terminal differentiation of cells is often accompanied by re...... Terminal differentiation of cells is often accompanied by repression of cellular proliferation, suggesting that there is a mechanism by which these cellular functions are coordinated. Macrophage differentiation is one model system in which this occurs; as macrophages differentiate, they also stop proliferating. Transcriptional regulation plays a key role in cell cycle progression as well as many differentiation processes. Ras stimulates cell cycle progression in part through Ets transcription factors that bind to cell cycle regulatory genes to activate their expression. Ets transcription factors also help to induce early macrophage differentiation. The activation of Ras signaling by M-CSF activates transcription of genes involved in differentiation through the coordinate expression of both Ets factors and AP-1. Other genes involved in cell cycle regulation involved the coordinate action of E2F-1 and Ets transcription factors. Mets is a factor related in sequence to Ets2 that is upregulated during macrophage differentiation. Increased expression of the Mets protein during macrophage differentiation allows the creation of heterodimers with DP103 to act as transcriptional repressors of cell cycle progression genes, recruiting corepressor to promoters they interact with. DP103 is a gene previously identified as an RNA helicase involved in RNA processing that interacts with EBNA factors from Epstein Barr Virus. The transcriptional repression involving Mets with DP103 is selective, and does not involve all Ets regulated genes. While cell cycle genes are repressed by Mets, other gene activated by Ets factors such as those involved in differentiation are not repressed by Mets. The transcriptional repression by Mets also involved members of the Rb family of tumor suppressors, such as p107 and p130. This requirement for additional factors involved in regulating proliferation may allow for another level of control on cell proliferation and coordination with differentiation. More...

HDAC5 related Reactome pathways (count: 0)

HDAC5 related interactors from protein-protein interaction data in HPRD (count: 37)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
HDAC5	BCOR	No	in vivo	10898795
HDAC5	GCM1	No	in vivo	16528103
HDAC5	NRIP1	No	in vitro;in vivo	15060175
HDAC5	SUV39H1	No	in vivo	12242305
HDAC5	MEF2C	No	in vitro	10737771
HDAC5	BCL6	Yes	in vitro;in vivo	11929873
HDAC5	CAMTA2	No	in vivo	16678093
HDAC5	NCOR2	No	in vitro;in vivo;yeast 2-hybrid	10869435
HDAC5	MEF2A	No	in vitro;in vivo	10748098 , 10737771
HDAC5	ANKRA2	No	in vitro;in vivo	15964851
HDAC5	GATA2	No	in vitro;in vivo	11567998
HDAC5	HR	No	in vivo;yeast 2-hybrid	11641275
HDAC5	HDAC3	No	in vitro;in vivo	10220385 , 11804585 , 11466315
HDAC5	HDAC5	Yes	in vivo	10898795
HDAC5	YWHAB	No	in vivo	10869435
HDAC5	MEF2D	No	in vitro;in vivo	12896970 , 10737771
HDAC5	NCOR1	No	in vitro;yeast 2-hybrid	10640275
HDAC5	BRMS1	No	in vivo	16919237
HDAC5	RUNX3	Yes	in vitro;in vivo	15138260
HDAC5	YWHAE	Yes	in vitro;in vivo;yeast 2-hybrid	10869435 , 11114197
HDAC5	SFN	No	in vivo;yeast 2-hybrid	15367659
HDAC5	PHB2	No	in vitro;in vivo	15140878
HDAC5	PRKD1	No	in vitro	15367659 , 11114197 , 11081517
HDAC5	RFXANK	No	in vitro;in vivo	15964851
HDAC5	CAMK1	No	in vitro	15367659 , 11114197 , 11081517
HDAC5	ZBTB16	Yes	in vitro;in vivo	15467736 , 11929873
HDAC5	ANKRD11	No	in vitro	15184363
HDAC5	CIITA	No	in vivo	15964851
HDAC5	KLF4	Yes	in vivo	18768922
HDAC5	EEF1G	No	yeast 2-hybrid	16169070
HDAC5	GABARAP	No	yeast 2-hybrid	16169070
HDAC5	GATA1	Yes	in vitro;in vivo	14668799
HDAC5	DDX20	No	in vitro;in vivo	12007404
HDAC5	UBC	No	in vitro;in vivo	12354939
HDAC5	CBX5	No	in vitro	12242305
HDAC5	NFKB2	No	in vitro;in vivo	12917325
HDAC5	GNB1	No	yeast 2-hybrid	16221676

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped BioCarta pathways