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Reviewed, UniProtKB/Swiss-Prot Q9UQL6 (HDAC5_HUMAN)

Last modified June 16, 2009. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Histone deacetylase 5
      Short name=HD5
    EC=3.5.1.98
Alternative name(s):
    Antigen NY-CO-9
Gene names
Name: HDAC5
Synonyms: KIAA0600
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1122 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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 by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors.

Catalytic activity

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

Subunit structure

Interacts with AHRR By similarity. Interacts with BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with KDM5B.

Subcellular location

Nucleus. Cytoplasm. Note: Shuttles between the nucleus and the cytoplasm. In muscle cells, it shuttles into the cytoplasm during myocyte differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-259 and Ser-498 by CaMK. Ref.8

Tissue specificity

Ubiquitous.

Domain

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

Post-translational modification

Phosphorylated by CaMK at Ser-259 and Ser-498. The phosphorylation is required for the export to the cytoplasm. Ref.8 Ref.9

Ubiquitinated. Polyubiquitination however does not lead to its degradation. Ref.11

Sequence similarities

Belongs to the histone deacetylase family. Type 2 subfamily.

Sequence caution

The sequence AAC18040.1 differs from that shown. Reason: Frameshift at position 1085.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UQL6-1)

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: Q9UQL6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     684-768: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11221122Histone deacetylase 5
PRO_0000114701

Regions

Region684 – 1028345Histone deacetylase
Motif1081 – 112242Nuclear export signal
Compositional bias47 – 526Poly-Gly
Compositional bias85 – 928Poly-Gln
Compositional bias596 – 5994Poly-Glu
Compositional bias1099 – 11046Poly-Ala

Sites

Active site8331 By similarity

Amino acid modifications

Modified residue2591Phosphoserine; by CaMK Ref.9
Modified residue4981Phosphoserine; by CaMK Ref.9

Natural variations

Alternative sequence684 – 76885Missing in isoform 2.
VSP_002081
Natural variant1371R → Q: dbSNP rs438096.
VAR_055903
Natural variant5651G → A: dbSNP rs33916560.
VAR_055904

Experimental info

Mutagenesis2591S → A: Reduces CaMK-dependent phosphorylation and the subsequent nuclear export. Abolishes nuclear export; when associated with A-498. Ref.8
Mutagenesis2791S → A: No effect. Ref.8
Mutagenesis4981S → A: Reduces CaMK-dependent phosphorylation and the subsequent nuclear export. Abolishes nuclear export; when associated with A-259. Ref.8
Mutagenesis6611S → A: No effect. Ref.8
Mutagenesis7131S → A: No effect. Ref.8
Mutagenesis10861V → A: Reduces CaMK-dependent nuclear export. Ref.10
Mutagenesis10921L → A: Reduces CaMK-dependent nuclear export. Ref.10
Sequence conflict5931E → D in BAA25526. Ref.2
Sequence conflict6711S → N Ref.5
Sequence conflict6841G → S Ref.5
Sequence conflict10261E → K Ref.5
Sequence conflict10741E → G Ref.5
Sequence conflict10931S → L Ref.5

Sequences

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

Last modified May 1, 2000. Version 1.
Checksum: CF4BBB8B9A288FEC

FASTA1,122121,992
        10         20         30         40         50         60 
MNSPNESDGM SGREPSLEIL PRTSLHSIPV TVEVKPVLPR AMPSSMGGGG GGSPSPVELR 

        70         80         90        100        110        120 
GALVGSVDPT LREQQLQQEL LALKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ 

       130        140        150        160        170        180 
QEMLAAKQQQ EMLAAKRQQE LEQQRQREQQ RQEELEKQRL EQQLLILRNK EKSKESAIAS 

       190        200        210        220        230        240 
TEVKLRLQEF LLSKSKEPTP GGLNHSLPQH PKCWGAHHAS LDQSSPPQSG PPGTPPSYKL 

       250        260        270        280        290        300 
PLPGPYDSRD DFPLRKTASE PNLKVRSRLK QKVAERRSSP LLRRKDGTVI STFKKRAVEI 

       310        320        330        340        350        360 
TGAGPGASSV CNSAPGSGPS SPNSSHSTIA ENGFTGSVPN IPTEMLPQHR ALPLDSSPNQ 

       370        380        390        400        410        420 
FSLYTSPSLP NISLGLQATV TVTNSHLTAS PKLSTQQEAE RQALQSLRQG GTLTGKFMST 

       430        440        450        460        470        480 
SSIPGCLLGV ALEGDGSPHG HASLLQHVLL LEQARQQSTL IAVPLHGQSP LVTGERVATS 

       490        500        510        520        530        540 
MRTVGKLPRH RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQLQ LGKILTKTGE 

       550        560        570        580        590        600 
LPRQPTTHPE ETEEELTEQQ EVLLGEGALT MPREGSTESE STQEDLEEED EEEDGEEEED 

       610        620        630        640        650        660 
CIQVKDEEGE SGAEEGPDLE EPGAGYKKLF SDAQPLQPLQ VYQAPLSLAT VPHQALGRTQ 

       670        680        690        700        710        720 
SSPAAPGGMK SPPDQPVKHL FTTGVVYDTF MLKHQCMCGN THVHPEHAGR IQSIWSRLQE 

       730        740        750        760        770        780 
TGLLSKCERI RGRKATLDEI QTVHSEYHTL LYGTSPLNRQ KLDSKKLLGP ISQKMYAVLP 

       790        800        810        820        830        840 
CGGIGVDSDT VWNEMHSSSA VRMAVGCLLE LAFKVAAGEL KNGFAIIRPP GHHAEESTAM 

       850        860        870        880        890        900 
GFCFFNSVAI TAKLLQQKLN VGKVLIVDWD IHHGNGTQQA FYNDPSVLYI SLHRYDNGNF 

       910        920        930        940        950        960 
FPGSGAPEEV GGGPGVGYNV NVAWTGGVDP PIGDVEYLTA FRTVVMPIAH EFSPDVVLVS 

       970        980        990       1000       1010       1020 
AGFDAVEGHL SPLGGYSVTA RCFGHLTRQL MTLAGGRVVL ALEGGHDLTA ICDASEACVS 

      1030       1040       1050       1060       1070       1080 
ALLSVELQPL DEAVLQQKPN INAVATLEKV IEIQSKHWSC VQKFAAGLGR SLREAQAGET 

      1090       1100       1110       1120 
EEAETVSAMA LLSVGAEQAQ AAAAREHSPR PAEEPMEQEP AL 

« Hide

Isoform 2.

Checksum: 5EC4148BF869A479
Show »

FASTA1,037112,205

References

« Hide 'large scale' references
[1]"Three proteins define a class of human histone deacetylases related to yeast Hda1p."
Grozinger C.M., Hassig C.A., Schreiber S.L.
Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999) [PubMed: 10220385] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Eye and Testis.
[5]"Characterization of human colon cancer antigens recognized by autologous antibodies."
Scanlan M.J., Chen Y.-T., Williamson B., Gure A.O., Stockert E., Gordan J.D., Tuereci O., Sahin U., Pfreundschuh M., Old L.J.
Int. J. Cancer 76:652-658(1998) [PubMed: 9610721] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 189-1122 (ISOFORM 1).
Tissue: Colon carcinoma.
[6]"Chromosomal organization and localization of the human histone deacetylase 5 gene (HDAC5)."
Mahlknecht U., Schnittger S., Ottmann O.G., Schoch C., Mosebach M., Hiddemann W., Hoelzer D.
Biochim. Biophys. Acta 1493:342-348(2000) [PubMed: 11018260] [Abstract]
Cited for: GENE ORGANIZATION.
[7]"BCoR, a novel corepressor involved in BCL-6 repression."
Huynh K.D., Fischle W., Verdin E., Bardwell V.J.
Genes Dev. 14:1810-1823(2000) [PubMed: 10898795] [Abstract]
Cited for: INTERACTION WITH BCOR.
[8]"Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation."
McKinsey T.A., Zhang C.-L., Lu J., Olson E.N.
Nature 408:106-111(2000) [PubMed: 11081517] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF SER-259; SER-279; SER-498; SER-661 AND SER-713.
[9]"Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5."
McKinsey T.A., Zhang C.-L., Olson E.N.
Proc. Natl. Acad. Sci. U.S.A. 97:14400-14405(2000) [PubMed: 11114197] [Abstract]
Cited for: INTERACTION WITH 14-3-3, PHOSPHORYLATION AT SER-259 AND SER-498.
[10]"Identification of a signal-responsive nuclear export sequence in class II histone deacetylases."
McKinsey T.A., Zhang C.-L., Olson E.N.
Mol. Cell. Biol. 21:6312-6321(2001) [PubMed: 11509672] [Abstract]
Cited for: NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF VAL-1086 AND LEU-1092.
[11]"Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes."
Hook S.S., Orian A., Cowley S.M., Eisenman R.N.
Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002) [PubMed: 12354939] [Abstract]
Cited for: UBIQUITINATION.
[12]"Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases."
Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K., Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., Freemont P., Taylor-Papadimitriou J.
Int. J. Cancer 121:265-275(2007) [PubMed: 17373667] [Abstract]
Cited for: INTERACTION WITH KDM5B.
[13]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF132608 mRNA. Translation: AAD29047.1.
AB011172 mRNA. Translation: BAA25526.2. Different initiation.
BC013140 mRNA. Translation: AAH13140.1. Different termination.
BC051824 mRNA. Translation: AAH51824.1.
AF039691 mRNA. Translation: AAC18040.1. Frameshift.
BK000028 Genomic DNA. Translation: DAA00017.1.
IPIIPI00217801.
IPI00328289.
RefSeqNP_001015053.1.
NP_005465.2.
UniGeneHs.438782

3D structure databases

SMRQ9UQL6. Positions 681-1063.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9UQL6. 6 interactions.

PTM databases

PhosphoSiteQ9UQL6.

Proteomic databases

PRIDEQ9UQL6.

Genome annotation databases

EnsemblENSG00000108840. Homo sapiens. [Contig view]
GeneID10014.
KEGGhsa:10014.

Organism-specific databases

GeneCardsGC17M039509.
H-InvDBHIX0013862.
HGNCHGNC:14068. HDAC5.
HPACAB019400.
MIM605315. gene.
PharmGKBPA29230.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ9UQL6.
HOVERGENQ9UQL6.

Enzyme and pathway databases

Pathway_Interaction_DBhdac_classi_pathway. Signaling events mediated by HDAC Class I.
hdac_classii_pathway. Signaling events mediated by HDAC Class II.
ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9UQL6.
BgeeQ9UQL6.
CleanExHS_HDAC5.
GermOnlineENSG00000108840. Homo sapiens.

Family and domain databases

InterProIPR000286. His_deacetylse.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
Gene3DG3DSA:3.40.800.20. His_deacetylse. 1 hit.
PANTHERPTHR10625. His_deacetylse. 1 hit.
PfamPF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSPR01270. HDASUPER.
ProtoNetSearch...

Other Resources

NextBio37831.
SOURCESearch...

Entry information

Entry nameHDAC5_HUMAN
AccessionPrimary (citable) accession number: Q9UQL6
Secondary accession number(s): O60340, O60528, Q96DY4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: June 16, 2009
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents