P56524 (HDAC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 4
Short name=HD4
EC=3.5.1.98

Gene names

Name:	HDAC4
Synonyms:	KIAA0288

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1084 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.6
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Subunit structure	Interacts with HDAC7 By similarity. Homodimer. Homodimerization via its N-terminal domain. Interacts with MEF2C, AHRR, and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner. Interacts with BTBD14B By similarity. Interacts with KDM5B. Interacts with MYOCD By similarity. Interacts with MORC2. Interacts with ANKRA2. Ref.5 Ref.6 Ref.10 Ref.11 Ref.12 Ref.17
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-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation. Ref.5 Ref.8
Tissue specificity	Ubiquitous.
Domain	The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.
Post-translational modification	Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-350 impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3. Ref.7 Ref.8 Ref.13 Ref.20 Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4. Ref.11
Involvement in disease	Brachydactyly-mental retardation syndrome (BDMR) [MIM:600430]: A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16
Sequence similarities	Belongs to the histone deacetylase family. HD type 2 subfamily.
Sequence caution	The sequence BAA22957.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Mental retardation
Domain	Coiled coil
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Traceable author statement PubMed 12711221. Source: UniProtKB cardiac muscle hypertrophy in response to stress Traceable author statement PubMed 17011572. Source: BHF-UCL chromatin remodeling Inferred from direct assay PubMed 18850004. Source: BHF-UCL histone H3 deacetylation Inferred from direct assay PubMed 12590135. Source: BHF-UCL histone H4 deacetylation Inferred from direct assay PubMed 12590135. Source: BHF-UCL inflammatory response Traceable author statement PubMed 12711221. Source: UniProtKB negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of glycolysis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of myotube differentiation Inferred from mutant phenotype PubMed 10983972. Source: BHF-UCL negative regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara negative regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 18850004. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 10869435. Source: BHF-UCL nervous system development Traceable author statement PubMed 12711221. Source: UniProtKB osteoblast development Inferred from electronic annotation. Source: Compara peptidyl-lysine deacetylation Inferred from direct assay PubMed 18614528. Source: BHF-UCL positive regulation of cell proliferation Inferred from mutant phenotype PubMed 18850004. Source: BHF-UCL positive regulation of protein sumoylation Inferred from direct assay PubMed 17696781. Source: UniProtKB positive regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 19071119. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 19071119. Source: BHF-UCL regulation of cardiac muscle contraction by calcium ion signaling Inferred from electronic annotation. Source: Compara regulation of protein binding Inferred from mutant phenotype PubMed 19071119. Source: BHF-UCL response to denervation involved in regulation of muscle adaptation Inferred from sequence or structural similarity. Source: BHF-UCL response to drug Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from mutant phenotype PubMed 19281832. Source: BHF-UCL skeletal system development Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	A band Inferred from electronic annotation. Source: Compara Z disc Inferred from electronic annotation. Source: Compara actomyosin Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay PubMed 10869435PubMed 19281832. Source: BHF-UCL cytosol Inferred from electronic annotation. Source: Compara histone deacetylase complex Inferred from direct assay PubMed 11804585. Source: BHF-UCL neuromuscular junction Inferred from electronic annotation. Source: Compara transcriptional repressor complex Inferred from direct assay PubMed 11804585. Source: BHF-UCL
Molecular_function	DNA binding Inferred from electronic annotation. Source: Compara NAD-dependent histone deacetylase activity (H3-K14 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K18 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K9 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H4-K16 specific) Inferred from electronic annotation. Source: EC histone deacetylase activity Inferred from direct assay PubMed 10869435. Source: BHF-UCL potassium ion binding Inferred from direct assay PubMed 18614528. Source: BHF-UCL transcription corepressor activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from direct assay PubMed 18614528. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	4	EBI-308629,EBI-608057
BCL6	P41182	3	EBI-308629,EBI-765407
BRMS1	Q9HCU9	2	EBI-308629,EBI-714781
MIF4GD	A9UHW6	4	EBI-308629,EBI-373498
UBE2I	P63279	3	EBI-308629,EBI-80168

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1084

1084

Histone deacetylase 4

PRO_0000114699

Regions

Region

118 – 313

196

Interaction with MEF2A

Region

655 – 1084

430

Histone deacetylase

Coiled coil

67 – 177

111

Potential

Motif

1051 – 1084

34

Nuclear export signal By similarity

Sites

Active site

803

1

By similarity

Metal binding

667

1

Zinc By similarity

Metal binding

669

1

Zinc By similarity

Metal binding

675

1

Zinc By similarity

Metal binding

751

1

Zinc By similarity

Amino acid modifications

Modified residue

246

1

Phosphoserine; by CaMK4 and SIK1 Ref.7

Modified residue

350

1

Phosphoserine Ref.15 Ref.20

Modified residue

467

1

Phosphoserine; by CaMK4 and SIK1 Ref.7

Modified residue

565

1

Phosphoserine

Modified residue

632

1

Phosphoserine; by CaMK4 Ref.7 Ref.14

Modified residue

633

1

Phosphoserine Ref.14

Cross-link

559

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.11

Natural variations

Natural variant

727

1

P → R in a breast cancer sample; somatic mutation. Ref.21

VAR_036042

Experimental info

Mutagenesis

246

1

S → A: Reduces phosphorylation and its subsequent nuclear export. Ref.7

Mutagenesis

467

1

S → A: Reduces phosphorylation and its subsequent nuclear export. Ref.7 Ref.8

Mutagenesis

559

1

K → R: Abolishes sumoylation and reduces the histone deacetylase activity. Ref.11

Mutagenesis

632

1

S → A: Reduces phosphorylation and its subsequent nuclear export. Ref.7 Ref.8

Mutagenesis

803

1

H → L: Abolishes histone deacetylase activity. Ref.6

Mutagenesis

1056

1

V → A: Reduces CaMK-dependent nuclear export. Ref.9

Mutagenesis

1062

1

L → A: Reduces CaMK-dependent nuclear export. Ref.9

Sequence conflict

373

1

A → T in AAD29046. Ref.1

Sequence conflict

373

1

A → T in BAA22957. Ref.2

Secondary structure

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1084

Helix Strand Turn

Details...

Helix

64 – 112

49

Helix

115 – 121

7

Turn

122 – 125

4

Helix

126 – 128

3

Turn

354 – 357

4

Beta strand

652 – 657

6

Helix

660 – 662

3

Beta strand

673 – 675

3

Helix

681 – 691

11

Helix

694 – 697

4

Beta strand

698 – 701

4

Helix

708 – 711

4

Turn

712 – 714

3

Helix

717 – 724

8

Helix

727 – 730

4

Helix

737 – 745

9

Beta strand

746 – 748

3

Beta strand

754 – 756

3

Helix

762 – 786

25

Beta strand

789 – 795

7

Beta strand

813 – 815

3

Helix

817 – 828

12

Beta strand

834 – 838

5

Beta strand

840 – 842

3

Helix

845 – 851

7

Beta strand

857 – 864

8

Helix

866 – 868

3

Beta strand

870 – 872

3

Helix

883 – 885

3

Beta strand

889 – 894

6

Beta strand

898 – 900

3

Helix

904 – 913

10

Helix

915 – 922

8

Beta strand

925 – 931

7

Beta strand

936 – 938

3

Turn

940 – 943

4

Helix

950 – 961

12

Helix

964 – 966

3

Beta strand

968 – 972

5

Helix

978 – 992

15

Helix

1002 – 1006

5

Helix

1011 – 1025

15

Helix

1029 – 1031

3

Helix

1042 – 1047

6

Sequences

	Sequence		Length	Mass (Da)
	P56524 [UniParc]. Last modified September 22, 2009. Version 3. Checksum: BB7FD37652D12398	FASTA	1,084	119,040
	10 20 30 40 50 60 MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPSAVPMD LRLDHQFSLP 70 80 90 100 110 120 VAEPALREQQ LQQELLALKQ KQQIQRQILI AEFQRQHEQL SRQHEAQLHE HIKQQQEMLA 130 140 150 160 170 180 MKHQQELLEH QRKLERHRQE QELEKQHREQ KLQQLKNKEK GKESAVASTE VKMKLQEFVL 190 200 210 220 230 240 NKKKALAHRN LNHCISSDPR YWYGKTQHSS LDQSSPPQSG VSTSYNHPVL GMYDAKDDFP 250 260 270 280 290 300 LRKTASEPNL KLRSRLKQKV AERRSSPLLR RKDGPVVTAL KKRPLDVTDS ACSSAPGSGP 310 320 330 340 350 360 SSPNNSSGSV SAENGIAPAV PSIPAETSLA HRLVAREGSA APLPLYTSPS LPNITLGLPA 370 380 390 400 410 420 TGPSAGTAGQ QDAERLTLPA LQQRLSLFPG THLTPYLSTS PLERDGGAAH SPLLQHMVLL 430 440 450 460 470 480 EQPPAQAPLV TGLGALPLHA QSLVGADRVS PSIHKLRQHR PLGRTQSAPL PQNAQALQHL 490 500 510 520 530 540 VIQQQHQQFL EKHKQQFQQQ QLQMNKIIPK PSEPARQPES HPEETEEELR EHQALLDEPY 550 560 570 580 590 600 LDRLPGQKEA HAQAGVQVKQ EPIESDEEEA EPPREVEPGQ RQPSEQELLF RQQALLLEQQ 610 620 630 640 650 660 RIHQLRNYQA SMEAAGIPVS FGGHRPLSRA QSSPASATFP VSVQEPPTKP RFTTGLVYDT 670 680 690 700 710 720 LMLKHQCTCG SSSSHPEHAG RIQSIWSRLQ ETGLRGKCEC IRGRKATLEE LQTVHSEAHT 730 740 750 760 770 780 LLYGTNPLNR QKLDSKKLLG SLASVFVRLP CGGVGVDSDT IWNEVHSAGA ARLAVGCVVE 790 800 810 820 830 840 LVFKVATGEL KNGFAVVRPP GHHAEESTPM GFCYFNSVAV AAKLLQQRLS VSKILIVDWD 850 860 870 880 890 900 VHHGNGTQQA FYSDPSVLYM SLHRYDDGNF FPGSGAPDEV GTGPGVGFNV NMAFTGGLDP 910 920 930 940 950 960 PMGDAEYLAA FRTVVMPIAS EFAPDVVLVS SGFDAVEGHP TPLGGYNLSA RCFGYLTKQL 970 980 990 1000 1010 1020 MGLAGGRIVL ALEGGHDLTA ICDASEACVS ALLGNELDPL PEKVLQQRPN ANAVRSMEKV 1030 1040 1050 1060 1070 1080 MEIHSKYWRC LQRTTSTAGR SLIEAQTCEN EEAETVTAMA SLSVGVKPAE KRPDEEPMEE EPPL

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Leukemia.
[2]	"Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins." Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Nomura N. DNA Res. 4:53-59(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Nomura N. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO N-TERMINUS.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"HDAC4 deacetylase associates with and represses the MEF2 transcription factor." Miska E.A., Karlsson C., Langley E., Nielsen S.J., Pines J., Kouzarides T. EMBO J. 18:5099-5107(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MEF2A.
[6]	"HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor." Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., Heng H.H., Th'ng J., Han J., Yang X.-J. Mol. Cell. Biol. 19:7816-7827(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MEF2C AND MEF2D, MUTAGENESIS OF HIS-803.
[7]	"Regulation of histone deacetylase 4 by binding of 14-3-3 proteins." Wang A.H., Kruhlak M.J., Wu J., Bertos N.R., Vezmar M., Posner B.I., Bazett-Jones D.P., Yang X.-J. Mol. Cell. Biol. 20:6904-6912(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-246; SER-467 AND SER-632, MUTAGENESIS OF SER-246; SER-467 AND SER-632.
[8]	"The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking." Zhao X., Ito A., Kane C.D., Liao T.-S., Bolger T.A., Lemrow S.M., Means A.R., Yao T.-P. J. Biol. Chem. 276:35042-35048(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF SER-467 AND SER-632.
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF VAL-1056 AND LEU-1062.
[10]	"The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases." Franco P.J., Farooqui M., Seto E., Wei L.-N. Mol. Endocrinol. 15:1318-1328(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NR2C1.
[11]	"The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase." Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E., Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A. EMBO J. 21:2682-2691(2002) [PubMed] [Europe PMC] [Abstract] Cited for: HOMODIMERIZATION, SUMOYLATION AT LYS-559, MUTAGENESIS OF LYS-559.
[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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KDM5B.
[13]	"Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells." Little G.H., Bai Y., Williams T., Poizat C. J. Biol. Chem. 282:7219-7231(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY CAMK2D.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632 AND SER-633, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[16]	"Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems." Williams S.R., Aldred M.A., Der Kaloustian V.M., Halal F., Gowans G., McLeod D.R., Zondag S., Toriello H.V., Magenis R.E., Elsea S.H. Am. J. Hum. Genet. 87:219-228(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN BDMR.
[17]	"Involvement of histone deacetylation in MORC2-mediated down-regulation of carbonic anhydrase IX." Shao Y., Li Y., Zhang J., Liu D., Liu F., Zhao Y., Shen T., Li F. Nucleic Acids Res. 38:2813-2824(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MORC2.
[18]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[19]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]	"Sequence-specific recognition of a PxLPxI/L motif by an ankyrin repeat tumbler lock." Xu C., Jin J., Bian C., Lam R., Tian R., Weist R., You L., Nie J., Bochkarev A., Tempel W., Tan C.S., Wasney G.A., Vedadi M., Gish G.D., Arrowsmith C.H., Pawson T., Yang X.J., Min J. Sci. Signal. 5:RA39-RA39(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 343-359 IN COMPLEX WITH ANKRA2, PHOSPHORYLATION AT SER-350.
[21]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-727.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF132607 mRNA. Translation: AAD29046.1.
AB006626 mRNA. Translation: BAA22957.2. Different initiation.
AC017028 Genomic DNA. No translation available.

IPI

IPI00010088.

RefSeq

NP_006028.2. NM_006037.3.

UniGene

Hs.20516.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H8N	X-ray	2.60	A/B/C/D	62-153	[»]
2O94	X-ray	3.00	A/B/C/D	62-153	[»]
2VQJ	X-ray	2.10	A	648-1057	[»]
2VQM	X-ray	1.80	A	648-1057	[»]
2VQO	X-ray	2.15	A/B	648-1057	[»]
2VQQ	X-ray	1.90	A/B	648-1057	[»]
2VQV	X-ray	3.30	A/B	648-1057	[»]
2VQW	X-ray	3.00	G	648-1057	[»]
3UXG	X-ray	1.85	B	343-359	[»]
3UZD	X-ray	1.86	B	343-359	[»]
3V31	X-ray	1.57	B	343-359	[»]

ProteinModelPortal

P56524.

ModBase

Search...

Protein-protein interaction databases

IntAct

P56524. 15 interactions.

MINT

MINT-104901.

STRING

9606.ENSP00000264606.

PTM databases

PhosphoSite

P56524.

Polymorphism databases

DMDM

259016348.

Proteomic databases

PaxDb

P56524.

PRIDE

P56524.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000345617; ENSP00000264606; ENSG00000068024.

GeneID

9759.

KEGG

hsa:9759.

UCSC

uc002vyk.4. human.

Organism-specific databases

CTD

9759.

GeneCards

GC02M239969.

HGNC

HGNC:14063. HDAC4.

HPA

CAB004431.

MIM

600430. phenotype.
605314. gene.

neXtProt

NX_P56524.

Orphanet

1001. 2q37 microdeletion syndrome.

PharmGKB

PA29229.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0123.

HOGENOM

HOG000232065.

HOVERGEN

HBG057100.

InParanoid

P56524.

KO

K11406.

OMA

VSFGGHR.

OrthoDB

EOG44MXRC.

PhylomeDB

P56524.

Enzyme and pathway databases

BRENDA

3.5.1.98. 2681.

Pathway_Interaction_DB

hdac_classi_pathway. Signaling events mediated by HDAC Class I.
hdac_classii_pathway. Signaling events mediated by HDAC Class II.
hdac_classiii_pathway. Signaling events mediated by HDAC Class III.
ranbp2pathway. Sumoylation by RanBP2 regulates transcriptional repression.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P56524.

Bgee

P56524.

CleanEx

HS_HDAC4.

Genevestigator

P56524.

GermOnline

ENSG00000068024. Homo sapiens.

Family and domain databases

Gene3D

3.40.800.20. 1 hit.

InterPro

IPR019154. Arb2_domain.
IPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]

PANTHER

PTHR10625. PTHR10625. 1 hit.

Pfam

PF09757. Arb2. 1 hit.
PF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]

PIRSF

PIRSF037911. HDAC_II_euk. 1 hit.

PRINTS

PR01270. HDASUPER.

ProtoNet

Search...

Other

BindingDB

P56524.

ChEMBL

CHEMBL3524.

EvolutionaryTrace

P56524.

GenomeRNAi

9759.

NextBio

36731.

SOURCE

Search...

Entry information

Entry name

HDAC4_HUMAN

Accession

Primary (citable) accession number: P56524
Secondary accession number(s): Q9UND6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	September 22, 2009
Last modified:	May 1, 2013
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.