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Q99N13 (HDAC9_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone deacetylase 9

Short name=HD9
EC=3.5.1.98
Alternative name(s):
Histone deacetylase 7B
Short name=HD7b
Histone deacetylase-related protein
MEF2-interacting transcription repressor MITR
Gene names
Name:Hdac9
Synonyms:Hdac7b, Hdrp, Mitr
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length588 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Devoided of intrinsic deacetylase activity, promotes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) by recruiting HDAC1 and HDAC3. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription, inhibits skeletal myogenesis and may be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter. Ref.4 Ref.5 Ref.7 Ref.8

Catalytic activity

Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.

Subunit structure

Homodimer. Interacts with ETV6 By similarity. Interacts with MEF2, HDAC1, HDAC3, HDAC4, HDAC5, CTBP1 and MAPK10. The phosphorylated form interacts with 14-3-3. Ref.1 Ref.7 Ref.8

Subcellular location

Nucleus Ref.4 Ref.6 Ref.7.

Tissue specificity

Expressed at high levels in heart, brain and spleen. Expressed in skeletal muscle. Ref.4 Ref.7

Developmental stage

At E10.5, expressed in heart, skeletal muscle and neural lineages. At E11.5, expressed in heart, dorsal root ganglia and neural tube. At E12.5, expressed in heart, skeletal muscle, dorsal root ganglia, neural tube and retina. Strongly up-regulated in muscle between E14 and E19 as a result of motor innervation. Ref.4 Ref.7 Ref.9

Induction

By MEF2 during muscle differentiation. Down-regulated by muscle denervation. Down-regulated by trichostatin A or sodium butyrate, and during neuronal apoptosis (at protein level). Ref.7 Ref.8 Ref.9

Post-translational modification

Sumoylated By similarity.

Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3-binding, impairs interaction with MEF2, and antagonizes antimyogenic activity. Phosphorylated on Ser-240 by DYRK1B; which impairs nuclear accumulation. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Ref.4 Ref.5 Ref.6

Disruption phenotype

Mice do not present any abnormality at early age but develop cardiac hypertrophy by eight months of age. Ref.5

Sequence similarities

Belongs to the histone deacetylase family. HD type 2 subfamily.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell activation

Traceable author statement PubMed 12711221. Source: UniProtKB

B cell differentiation

Traceable author statement PubMed 12711221. Source: UniProtKB

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

chromatin modification

Traceable author statement PubMed 12711221. Source: UniProtKB

heart development

Inferred from genetic interaction PubMed 15367668. Source: MGI

histone H3 deacetylation

Inferred from electronic annotation. Source: Ensembl

histone H4 deacetylation

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Traceable author statement PubMed 12711221. Source: UniProtKB

negative regulation of striated muscle tissue development

Traceable author statement PubMed 12711221. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.4. Source: MGI

negative regulation of transcription, DNA-templated

Traceable author statement PubMed 12711221. Source: UniProtKB

nervous system development

Traceable author statement PubMed 12711221. Source: UniProtKB

peptidyl-lysine deacetylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration involved in sprouting angiogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of skeletal muscle fiber development

Inferred from genetic interaction PubMed 17786239. Source: MGI

regulation of striated muscle cell differentiation

Inferred from genetic interaction PubMed 17786239. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Traceable author statement PubMed 12711221. Source: UniProtKB

histone deacetylase complex

Traceable author statement PubMed 12711221. Source: UniProtKB

histone methyltransferase complex

Inferred from direct assay PubMed 12242305. Source: BHF-UCL

nucleus

Traceable author statement PubMed 12711221. Source: UniProtKB

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionhistone deacetylase activity

Traceable author statement PubMed 12711221. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15102471. Source: IntAct

repressing transcription factor binding

Inferred from physical interaction PubMed 12242305. Source: BHF-UCL

transcription corepressor activity

Inferred from direct assay Ref.1. Source: MGI

transcription factor binding

Traceable author statement PubMed 12711221. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Pcbp1P603356EBI-645361,EBI-309059

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99N13-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q99N13-2)

Also known as: Hdrpa;

The sequence of this isoform differs from the canonical sequence as follows:
     219-262: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q99N13-3)

The sequence of this isoform differs from the canonical sequence as follows:
     177-178: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 588588Histone deacetylase 9
PRO_0000114711

Regions

Region23 – 275Interaction with CTBP1
Region136 – 15419Interaction with MEF2
Region175 – 343169Interaction with MAPK10
Region218 – 26144Interaction with ETV6 By similarity

Amino acid modifications

Modified residue221Phosphoserine By similarity
Modified residue2201Phosphoserine Ref.4 Ref.5
Modified residue2401Phosphoserine; by DYRK1B Ref.6
Modified residue4501Phosphoserine Ref.4 Ref.5

Natural variations

Alternative sequence177 – 1782Missing in isoform 3.
VSP_029173
Alternative sequence219 – 26244Missing in isoform 2.
VSP_023769

Experimental info

Mutagenesis25 – 262DL → AS: Abolishes binding to CTBP1 and impairs function in transcription repression. Ref.1
Sequence conflict1201R → K in AAK15027. Ref.2
Sequence conflict1201R → K in AAL86358. Ref.2
Sequence conflict1361R → K in AAK15027. Ref.2
Sequence conflict1361R → K in AAL86358. Ref.2
Sequence conflict3881N → T in AAH98187. Ref.3
Sequence conflict5231N → T in AAG48332. Ref.1

Secondary structure

... 588
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 20, 2007. Version 2.
Checksum: 4ED7FA9F02BD4621

FASTA58865,687
        10         20         30         40         50         60 
MHSMISSVDV KSEVPMGLEP ISPLDLRTDL RMMMPVVDPV VREKQLQQEL LLIQQQQQIQ 

        70         80         90        100        110        120 
KQLLIAEFQK QHENLTRQHQ AQLQEHIKEL LAIKQQQELL EKEQKLEQQR QEQEVERHRR 

       130        140        150        160        170        180 
EQQLPPLRGK DRGRERAVAS TEVKQKLQEF LLSKSATKDT PTNGKNHSVG RHPKLWYTAA 

       190        200        210        220        230        240 
HHTSLDQSSP PLSGTSPSYK YTLPGAQDSK DDFPLRKTAS EPNLKVRSRL KQKVAERRSS 

       250        260        270        280        290        300 
PLLRRKDGNL VTSFKKRVFE VAESSVSSSS PGSGPSSPNN GPAGNVTENE ASALPPTPHP 

       310        320        330        340        350        360 
EQLVPQQRIL IHEDSMNLLS LYTSPSLPNI TLGLPAVPSP LNASNSLKDK QKCETQMLRQ 

       370        380        390        400        410        420 
GVPLPSQYGS SIAASSSHVH VAMEGKPNSS HQALLQHLLL KEQMRQQKLL VAGGVPLHPQ 

       430        440        450        460        470        480 
SPLATKERIS PGIRGTHKLP RHRPLNRTQS APLPQSTLAQ LVIQQQHQQF LEKQKQYQQQ 

       490        500        510        520        530        540 
IHMNKLLSKS IEQLKQPGSH LEEAEEELQG DQSMEDRAAS KDNSARSDSS ACVEDTLGQV 

       550        560        570        580 
GAVKVKEEPV DSDEDAQIQE MECGEQAAFM QQVIGKDLAP GFVIKVII 

« Hide

Isoform 2 (Hdrpa) [UniParc].

Checksum: 60B1203BC91D87D0
Show »

FASTA54460,609
Isoform 3 [UniParc].

Checksum: E92E1B8ED6AD5C99
Show »

FASTA58665,422

References

« Hide 'large scale' references
[1]"Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor."
Zhang C.L., McKinsey T.A., Lu J.R., Olson E.N.
J. Biol. Chem. 276:35-39(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), HOMODIMERIZATION, INTERACTION WITH CTBP1; HDAC1; HDAC3; HDAC4 AND HDAC5, MUTAGENESIS OF 25-ASP-LEU-26.
Strain: NIH Swiss.
Tissue: Embryonic heart.
[2]"Cloning of the mouse HDRP cDNA."
Zhou X., Richon V.M., Rifkind R.A., Marks P.A.
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Strain: Swiss Webster / NIH.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6.
Tissue: Retina.
[4]"The transcriptional corepressor MITR is a signal-responsive inhibitor of myogenesis."
Zhang C.L., McKinsey T.A., Olson E.N.
Proc. Natl. Acad. Sci. U.S.A. 98:7354-7359(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-220 AND SER-450, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
[5]"Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy."
Zhang C.L., McKinsey T.A., Chang S., Antos C.L., Hill J.A., Olson E.N.
Cell 110:479-488(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-220 AND SER-450, FUNCTION, DISRUPTION PHENOTYPE.
[6]"Mirk/dyrk1B decreases the nuclear accumulation of class II histone deacetylases during skeletal muscle differentiation."
Deng X., Ewton D.Z., Mercer S.E., Friedman E.
J. Biol. Chem. 280:4894-4905(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-240, SUBCELLULAR LOCATION.
[7]"Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression."
Mejat A., Ramond F., Bassel-Duby R., Khochbin S., Olson E.N., Schaeffer L.
Nat. Neurosci. 8:313-321(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOWN-REGULATION BY DENERVATION, INTERACTION WITH HDAC1 AND HDAC3, SUBCELLULAR LOCATION.
[8]"Neuroprotection by histone deacetylase-related protein."
Morrison B.E., Majdzadeh N., Zhang X., Lyles A., Bassel-Duby R., Olson E.N., D'Mello S.R.
Mol. Cell. Biol. 26:3550-3564(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DOWN-REGULATION BY NEURONAL APOPTOSIS, FUNCTION, INTERACTION WITH HDAC1 AND MAPK10.
[9]"Regulation of HDAC9 gene expression by MEF2 establishes a negative-feedback loop in the transcriptional circuitry of muscle differentiation."
Haberland M., Arnold M.A., McAnally J., Phan D., Kim Y., Olson E.N.
Mol. Cell. Biol. 27:518-525(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY MEF2, DEVELOPMENTAL STAGE.
[10]"Mechanism of recruitment of class II histone deacetylases by myocyte enhancer factor-2."
Han A., He J., Wu Y., Liu J.O., Chen L.
J. Mol. Biol. 345:91-102(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 139-158 IN COMPLEX WITH MEF2 AND DNA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF324492 mRNA. Translation: AAG48332.1.
AF235053 mRNA. Translation: AAK15027.1.
AF279371 mRNA. Translation: AAL86358.1.
BC098187 mRNA. Translation: AAH98187.1.
CCDSCCDS36432.1. [Q99N13-1]
RefSeqNP_077038.2. NM_024124.3.
UniGeneMm.310551.
Mm.483009.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TQEX-ray2.70X/Y139-158[»]
ProteinModelPortalQ99N13.
SMRQ99N13. Positions 37-101.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid219748. 5 interactions.
DIPDIP-41905N.
IntActQ99N13. 5 interactions.
MINTMINT-146908.

Chemistry

BindingDBQ99N13.

PTM databases

PhosphoSiteQ99N13.

Proteomic databases

PaxDbQ99N13.
PRIDEQ99N13.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000110819; ENSMUSP00000106443; ENSMUSG00000004698.
GeneID79221.
KEGGmmu:79221.
UCSCuc007nja.1. mouse. [Q99N13-3]
uc007njb.1. mouse. [Q99N13-2]
uc007njc.2. mouse. [Q99N13-1]

Organism-specific databases

CTD9734.
MGIMGI:1931221. Hdac9.

Phylogenomic databases

eggNOGCOG0123.
GeneTreeENSGT00530000062809.
HOGENOMHOG000232065.
HOVERGENHBG057100.
KOK11409.
OrthoDBEOG7RFTH5.
PhylomeDBQ99N13.
TreeFamTF106174.

Gene expression databases

BgeeQ99N13.
CleanExMM_HDAC9.
GenevestigatorQ99N13.

Family and domain databases

InterProIPR000286. His_deacetylse.
IPR024643. Hist_deacetylase_Gln_rich_N.
[Graphical view]
PANTHERPTHR10625. PTHR10625. 1 hit.
PfamPF12203. HDAC4_Gln. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHDAC9. mouse.
EvolutionaryTraceQ99N13.
NextBio349885.
PROQ99N13.
SOURCESearch...

Entry information

Entry nameHDAC9_MOUSE
AccessionPrimary (citable) accession number: Q99N13
Secondary accession number(s): Q4QQN7, Q8R4Y6, Q9EPT2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: March 20, 2007
Last modified: July 9, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot