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Q6NZM9 (HDAC4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 4

Short name=HD4
EC=3.5.1.98
Gene names
Name:Hdac4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1076 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D By similarity.

Catalytic activity

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

Subunit structure

Interacts with HDAC7. Homodimer. Homodimerization via its N-terminal domain. Interacts with MEF2C and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner. Interacts with BTBD14B. Interacts with KDM5B. Interacts with ANKRA2 By similarity. Interacts with AHRR. Interacts with MYOCD. Ref.3 Ref.4

Subcellular location

Nucleus. Cytoplasm. Note: Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-245, Ser-465 and Ser-629 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation By similarity.

Domain

The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm By similarity.

Post-translational modification

Phosphorylated by CaMK4 at Ser-245, Ser-465 and Ser-629. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-349 impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3 By similarity. Ref.5 Ref.6

Sumoylation on Lys-556 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.

Sequence similarities

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

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   LigandMetal-binding
Zinc
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromatin remodeling

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from direct assay PubMed 15537544. Source: MGI

negative regulation of glycolytic process

Inferred from mutant phenotype PubMed 19109424. Source: BHF-UCL

negative regulation of myotube differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast differentiation

Inferred from mutant phenotype PubMed 15990875. Source: MGI

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17873280. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 16260608. Source: MGI

osteoblast development

Inferred from mutant phenotype PubMed 15990875. Source: MGI

peptidyl-lysine deacetylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein sumoylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19109424. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 19109424. Source: BHF-UCL

regulation of cardiac muscle contraction by calcium ion signaling

Inferred from mutant phenotype PubMed 18250163. Source: MGI

regulation of protein binding

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

response to denervation involved in regulation of muscle adaptation

Inferred from mutant phenotype PubMed 19109424. Source: BHF-UCL

response to drug

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Inferred from mutant phenotype PubMed 15537544. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentA band

Inferred from electronic annotation. Source: Ensembl

Z disc

Inferred from electronic annotation. Source: Ensembl

actomyosin

Inferred from direct assay PubMed 18250163. Source: MGI

cytoplasm

Inferred from mutant phenotype PubMed 19109424. Source: BHF-UCL

cytosol

Inferred from direct assay PubMed 17761942. Source: MGI

histone deacetylase complex

Inferred from electronic annotation. Source: Ensembl

neuromuscular junction

Inferred from direct assay PubMed 17873280. Source: MGI

nucleus

Inferred from mutant phenotype PubMed 19109424. Source: BHF-UCL

transcriptional repressor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Inferred from direct assay PubMed 16260608. Source: MGI

NAD-dependent histone deacetylase activity (H3-K14 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K18 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K9 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H4-K16 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

core promoter binding

Inferred from electronic annotation. Source: Ensembl

potassium ion binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.3. Source: UniProtKB

protein deacetylase activity

Inferred from direct assay PubMed 18250163. Source: MGI

protein kinase binding

Inferred from physical interaction Ref.6. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

transcription corepressor activity

Inferred from genetic interaction PubMed 15990875. Source: MGI

transcription factor binding

Inferred from physical interaction PubMed 10748098. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Runx2Q087753EBI-646397,EBI-903354

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6NZM9-1)

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: Q6NZM9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-171: Missing.
     732-732: S → SKKLLG
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10761076Histone deacetylase 4
PRO_0000281033

Regions

Region117 – 312196Interaction with MEF2A By similarity
Region652 – 1076425Histone deacetylase By similarity
Coiled coil66 – 169104 Potential
Motif1043 – 107634Nuclear export signal By similarity
Compositional bias464 – 49936Gln-rich
Compositional bias561 – 5688Poly-Glu

Sites

Active site7951 By similarity
Metal binding6641Zinc By similarity
Metal binding6661Zinc By similarity
Metal binding6721Zinc By similarity
Metal binding7431Zinc By similarity

Amino acid modifications

Modified residue2451Phosphoserine; by CaMK4 and SIK1
Modified residue3491Phosphoserine By similarity
Modified residue4651Phosphoserine; by CaMK4 and SIK1 Ref.6 Ref.7
Modified residue5621Phosphoserine By similarity
Modified residue6291Phosphoserine; by CaMK4 By similarity
Modified residue6301Phosphoserine By similarity
Cross-link556Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence1 – 171171Missing in isoform 2.
VSP_023952
Alternative sequence7321S → SKKLLG in isoform 2.
VSP_023953

Experimental info

Sequence conflict5691A → S in BAE33147. Ref.1
Sequence conflict9041R → K in BAE33147. Ref.1

Sequences

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

Last modified July 5, 2004. Version 1.
Checksum: A3CCC3CCCBB903A0

FASTA1,076118,562
        10         20         30         40         50         60 
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPTAVPMD LRLDHQFSLP 

        70         80         90        100        110        120 
LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS RQHEAQLHEH IKQQQEMLAM 

       130        140        150        160        170        180 
KHQQELLEHQ RKLERHRQEQ ELEKQHREQK LQQLKNKEKG KESAVASTEV KMKLQEFVLN 

       190        200        210        220        230        240 
KKKALAHRNL NHCISSDPRY WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL 

       250        260        270        280        290        300 
RKTASEPNLK LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS 

       310        320        330        340        350        360 
SPNSSSGNVS TENGIAPTVP SAPAETSLAH RLVTREGSVA PLPLYTSPSL PNITLGLPAT 

       370        380        390        400        410        420 
GPAAGAAGQQ DAERLALPAL QQRILFPGTH LTPYLSTSPL ERDGAAAHNP LLQHMVLLEQ 

       430        440        450        460        470        480 
PPTQTPLVTG LGALPLHSQS LVGADRVSPS IHKLRQHRPL GRTQSAPLPQ NAQALQHLVI 

       490        500        510        520        530        540 
QQQHQQFLEK HKQQFQQQQL HLSKIISKPS EPPRQPESHP EETEEELREH QALLDEPYLD 

       550        560        570        580        590        600 
RLPGQKEPSL AGVQVKQEPI ESEEEEAEAT RETEPGQRPA TEQELLFRQQ ALLLEQQRIH 

       610        620        630        640        650        660 
QLRNYQASME AAGIPVSFGS HRPLSRAQSS PASATFPMSV QEPPTKPRFT TGLVYDTLML 

       670        680        690        700        710        720 
KHQCTCGNTN SHPEHAGRIQ SIWSRLQETG LRGKCECIRG RKATLEELQT VHSEAHTLLY 

       730        740        750        760        770        780 
GTNPLNRQKL DSSLTSVFVR LPCGGVGVDS DTIWNEVHSS GAARLAVGCV VELVFKVATG 

       790        800        810        820        830        840 
ELKNGFAVVR PPGHHAEEST PMGFCYFNSV AVAAKLLQQR LNVSKILIVD WDVHHGNGTQ 

       850        860        870        880        890        900 
QAFYNDPNVL YMSLHRYDDG NFFPGSGAPD EVGTGPGVGF NVNMAFTGGL EPPMGDAEYL 

       910        920        930        940        950        960 
AAFRTVVMPI ANEFAPDVVL VSSGFDAVEG HPTPLGGYNL SAKCFGYLTK QLMGLAGGRL 

       970        980        990       1000       1010       1020 
VLALEGGHDL TAICDASEAC VSALLGNELE PLPEKVLHQR PNANAVHSME KVMDIHSKYW 

      1030       1040       1050       1060       1070 
RCLQRLSSTV GHSLIEAQKC EKEEAETVTA MASLSVGVKP AEKRSEEEPM EEEPPL 

« Hide

Isoform 2 [UniParc].

Checksum: 80C1A8CA5567EE19
Show »

FASTA91099,124

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J and NOD.
Tissue: Dendritic cell, Epididymis and Testis.
[2]"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: Brain.
[3]"Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin."
Cao D., Wang Z., Zhang C.L., Oh J., Xing W., Li S., Richardson J.A., Wang D.Z., Olson E.N.
Mol. Cell. Biol. 25:364-376(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOCD.
[4]"Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5."
Oshima M., Mimura J., Yamamoto M., Fujii-Kuriyama Y.
Biochem. Biophys. Res. Commun. 364:276-282(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AHRR.
[5]"CaMKIIdelta isoforms differentially affect calcium handling but similarly regulate HDAC/MEF2 transcriptional responses."
Zhang T., Kohlhaas M., Backs J., Mishra S., Phillips W., Dybkova N., Chang S., Ling H., Bers D.M., Maier L.S., Olson E.N., Brown J.H.
J. Biol. Chem. 282:35078-35087(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CAMK2D.
[6]"SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes."
Berdeaux R., Goebel N., Banaszynski L., Takemori H., Wandless T., Shelton G.D., Montminy M.
Nat. Med. 13:597-603(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-465 AND SER-465.
[7]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-465, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK029933 mRNA. Translation: BAE43272.1.
AK155250 mRNA. Translation: BAE33147.1.
AK162369 mRNA. Translation: BAE36877.1.
BC066052 mRNA. Translation: AAH66052.1.
CCDSCCDS48324.1. [Q6NZM9-1]
RefSeqNP_997108.1. NM_207225.1. [Q6NZM9-1]
UniGeneMm.318567.

3D structure databases

ProteinModelPortalQ6NZM9.
SMRQ6NZM9. Positions 62-128, 649-1023.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid229009. 14 interactions.
DIPDIP-36317N.
IntActQ6NZM9. 6 interactions.
MINTMINT-5183788.

PTM databases

PhosphoSiteQ6NZM9.

Proteomic databases

PaxDbQ6NZM9.
PRIDEQ6NZM9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000008995; ENSMUSP00000008995; ENSMUSG00000026313. [Q6NZM9-1]
GeneID208727.
KEGGmmu:208727.
UCSCuc007cbe.2. mouse. [Q6NZM9-2]
uc007cbf.2. mouse. [Q6NZM9-1]

Organism-specific databases

CTD9759.
MGIMGI:3036234. Hdac4.

Phylogenomic databases

eggNOGCOG0123.
GeneTreeENSGT00530000062809.
HOGENOMHOG000232065.
HOVERGENHBG057100.
InParanoidQ6NZM9.
KOK11406.
OMAVSFGGHR.
OrthoDBEOG7RFTH5.
PhylomeDBQ6NZM9.
TreeFamTF106174.

Gene expression databases

BgeeQ6NZM9.
CleanExMM_HDAC4.
GenevestigatorQ6NZM9.

Family and domain databases

Gene3D3.40.800.20. 1 hit.
InterProIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERPTHR10625. PTHR10625. 1 hit.
PfamPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSPR01270. HDASUPER.
ProtoNetSearch...

Other

NextBio372399.
PROQ6NZM9.
SOURCESearch...

Entry information

Entry nameHDAC4_MOUSE
AccessionPrimary (citable) accession number: Q6NZM9
Secondary accession number(s): Q3TRZ9, Q3U2J3, Q3V3Y4
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 91 of the entry and version 1 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

MGD cross-references

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