Human Gene HDAC8 (ENST00000373573.9)
  Description: Homo sapiens histone deacetylase 8 (HDAC8), transcript variant 1, mRNA. (from RefSeq NM_018486)
RefSeq Summary (NM_018486): Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009].
Gencode Transcript: ENST00000373573.9
Gencode Gene: ENSG00000147099.21
Transcript (Including UTRs)
   Position: hg38 chrX:72,329,516-72,572,843 Size: 243,328 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chrX:72,330,054-72,572,761 Size: 242,708 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:72,329,516-72,572,843)mRNA (may differ from genome)Protein (377 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
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HPRDLynxMGImyGene2neXtProtOMIM
PubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: HDAC8_HUMAN
DESCRIPTION: RecName: Full=Histone deacetylase 8; Short=HD8; EC=3.5.1.98;
FUNCTION: Responsible for 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. May play a role in smooth muscle cell contractility.
CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
COFACTOR: Binds 1 divalent metal cation per subunit.
ENZYME REGULATION: Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4- phenylacetyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4- dimethylamino-N-(6-hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4- dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl- benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'- hydroxyamide (CRA-A) and butyrate.
SUBUNIT: Interacts with PEPB2-MYH11, a fusion protein consisting of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11 produced by the inversion Inv(16)(p13q22), a translocation associated with acute myeloid leukemia of M4EO subtype. The PEPB2-MYH1 fusion protein also interacts with RUNX1, a well known transcriptional regulator, suggesting that the interaction with HDAC8 may participate in the conversion of RUNX1 into a constitutive transcriptional repressor. Interacts with CBFA2T3. Interacts with phosphorylated SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated degradation. Associates with alpha-SMA (smooth muscle alpha-actin).
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Excluded from the nucleoli. Found in the cytoplasm of cells showing smooth muscle differentiation.
TISSUE SPECIFICITY: Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas and also in liver, lung, placenta, prostate and kidney.
PTM: Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4.
SIMILARITY: Belongs to the histone deacetylase family. HD type 1 subfamily.

-  MalaCards Disease Associations
  MalaCards Gene Search: HDAC8
Diseases sorted by gene-association score: cornelia de lange syndrome 5* (1231), wilson-turner syndrome* (247), cornelia de lange syndrome* (200), microcephaly* (126), mental retardation, x-linked, syndromic, wilson-turner type* (100), hdac8-related cornelia de lange syndrome* (100), kbg syndrome (6), intellectual disability (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.26 RPKM in Adrenal Gland
Total median expression: 134.68 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -21.0082-0.256 Picture PostScript Text
3' UTR -140.90538-0.262 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000286 - His_deacetylse
IPR003084 - His_deacetylse_1
IPR023801 - His_deacetylse_dom

Pfam Domains:
PF00850 - Histone deacetylase domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1T64
- X-ray MuPIT

1T67
- X-ray MuPIT

1T69
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1VKG - X-ray MuPIT 1W22 - X-ray MuPIT 2V5W - X-ray MuPIT
2V5X - X-ray MuPIT 3EW8 - X-ray MuPIT 3EWF - X-ray MuPIT
3EZP - X-ray MuPIT 3EZT - X-ray MuPIT 3F06 - X-ray MuPIT
3F07 - X-ray MuPIT 3F0R - X-ray MuPIT 3MZ3 - X-ray MuPIT
3MZ4 - X-ray MuPIT 3MZ6 - X-ray MuPIT 3MZ7 - X-ray MuPIT
3RQD - X-ray MuPIT 3SFF - X-ray MuPIT 3SFH - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9BY41
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003682 chromatin binding
GO:0004407 histone deacetylase activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0016787 hydrolase activity
GO:0019213 deacetylase activity
GO:0030544 Hsp70 protein binding
GO:0032041 NAD-dependent histone deacetylase activity (H3-K14 specific)
GO:0046872 metal ion binding
GO:0051879 Hsp90 protein binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006325 chromatin organization
GO:0006333 chromatin assembly or disassembly
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007062 sister chromatid cohesion
GO:0010629 negative regulation of gene expression
GO:0016575 histone deacetylation
GO:0031397 negative regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0032204 regulation of telomere maintenance
GO:0035984 cellular response to trichostatin A
GO:0045668 negative regulation of osteoblast differentiation
GO:0070932 histone H3 deacetylation
GO:0071922 regulation of cohesin loading
GO:1904322 cellular response to forskolin
GO:2000616 negative regulation of histone H3-K9 acetylation

Cellular Component:
GO:0000118 histone deacetylase complex
GO:0000228 nuclear chromosome
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AF245664 - Homo sapiens histone deacetylase 8 mRNA, complete cds.
BC050433 - Homo sapiens histone deacetylase 8, mRNA (cDNA clone MGC:54166 IMAGE:5761745), complete cds.
BC023642 - Homo sapiens cDNA clone IMAGE:4906157, **** WARNING: chimeric clone ****.
AJ277724 - Homo sapiens mRNA for histone deacetylase 8 (HDAC8 gene).
AF230097 - Homo sapiens class I histone deacetylase (HDAC8) mRNA, complete cds.
AK298767 - Homo sapiens cDNA FLJ58211 complete cds, highly similar to Histone deacetylase 8.
AK296641 - Homo sapiens cDNA FLJ58011 complete cds, highly similar to Histone deacetylase 8.
KJ899208 - Synthetic construct Homo sapiens clone ccsbBroadEn_08602 HDAC8 gene, encodes complete protein.
EU446822 - Synthetic construct Homo sapiens clone IMAGE:100070348; IMAGE:100012031; FLH257249.01L histone deacetylase 8 (HDAC8) gene, encodes complete protein.
EU832800 - Synthetic construct Homo sapiens clone HAIB:100067829; DKFZo008D0733 histone deacetylase 8 protein (HDAC8) gene, encodes complete protein.
GQ129378 - Synthetic construct Homo sapiens clone HAIB:100068489; DKFZo004D0734 histone deacetylase 8 protein (HDAC8) gene, partial cds.
AB527476 - Synthetic construct DNA, clone: pF1KB7636, Homo sapiens HDAC8 gene for histone deacetylase 8, without stop codon, in Flexi system.
AK294903 - Homo sapiens cDNA FLJ57974 complete cds, highly similar to Histone deacetylase 8.
CU690678 - Synthetic construct Homo sapiens gateway clone IMAGE:100021377 5' read HDAC8 mRNA.
AY429539 - Homo sapiens HDAC8v_1 mRNA sequence; alternatively spliced.
AK074326 - Homo sapiens cDNA FLJ23746 fis, clone HEP15972, highly similar to Homo sapiens mRNA for histone deacetylase 8.
AK300895 - Homo sapiens cDNA FLJ60901 complete cds, highly similar to Histone deacetylase 8.
JD182752 - Sequence 163776 from Patent EP1572962.
JD437377 - Sequence 418401 from Patent EP1572962.
JD131288 - Sequence 112312 from Patent EP1572962.
JD365580 - Sequence 346604 from Patent EP1572962.
JD043835 - Sequence 24859 from Patent EP1572962.
JD187696 - Sequence 168720 from Patent EP1572962.
JD214196 - Sequence 195220 from Patent EP1572962.
JD532954 - Sequence 513978 from Patent EP1572962.
JD515606 - Sequence 496630 from Patent EP1572962.
AK057569 - Homo sapiens cDNA FLJ33007 fis, clone THYMU1000318, weakly similar to Homo sapiens mRNA for histone deacetylase 8 (HDAC8 gene).
AF212246 - Homo sapiens CDA07 mRNA, complete cds.
JD382783 - Sequence 363807 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9BY41 (Reactome details) participates in the following event(s):

R-HSA-2545203 Deacetylation of cleaved cohesin
R-HSA-2545253 Deacetylation of cohesin
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-68882 Mitotic Anaphase
R-HSA-68877 Mitotic Prometaphase
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-68886 M Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle
R-HSA-2545203 Deacetylation of cleaved cohesin
R-HSA-2545253 Deacetylation of cohesin
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-68882 Mitotic Anaphase
R-HSA-68877 Mitotic Prometaphase
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-68886 M Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle
R-HSA-2545203 Deacetylation of cleaved cohesin
R-HSA-2545253 Deacetylation of cohesin
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-68882 Mitotic Anaphase
R-HSA-68877 Mitotic Prometaphase
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-68886 M Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle
R-HSA-3782637 HDAC8 deacetylates histones
R-HSA-1912388 NICD1 displaces co-repressor complex from RBPJ (CSL)
R-HSA-2220982 NICD1 PEST domain mutants displace co-repressor complex from RBPJ (CSL)
R-HSA-3214815 HDACs deacetylate histones
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3247509 Chromatin modifying enzymes
R-HSA-1980143 Signaling by NOTCH1
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-4839726 Chromatin organization
R-HSA-157118 Signaling by NOTCH
R-HSA-2644603 Signaling by NOTCH1 in Cancer
R-HSA-162582 Signal Transduction
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: A6NET3, A8MQ62, B4DKN0, B4DV22, CDA07, ENST00000373573.1, ENST00000373573.2, ENST00000373573.3, ENST00000373573.4, ENST00000373573.5, ENST00000373573.6, ENST00000373573.7, ENST00000373573.8, HDAC8_HUMAN, HDACL1, NM_018486, Q86VC8, Q9BY41, Q9NP76, Q9NYH4, uc004eau.1, uc004eau.2, uc004eau.3, uc004eau.4, uc004eau.5
UCSC ID: ENST00000373573.9
RefSeq Accession: NM_018486
Protein: Q9BY41 (aka HDAC8_HUMAN or HDA8_HUMAN)
CCDS: CCDS14420.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene HDAC8:
cdh-ov (Congenital Diaphragmatic Hernia Overview)
cdls (Cornelia de Lange Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.