Q99N13 (HDAC9_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	588 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	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 cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara heart development Inferred from genetic interaction PubMed 15367668. Source: MGI histone H3 deacetylation Inferred from electronic annotation. Source: Compara histone H4 deacetylation Inferred from electronic annotation. Source: Compara 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 nervous system development Traceable author statement PubMed 12711221. Source: UniProtKB peptidyl-lysine deacetylation Inferred from electronic annotation. Source: Compara positive regulation of cell migration involved in sprouting angiogenesis Inferred from electronic annotation. Source: Compara regulation of skeletal muscle fiber development Inferred from genetic interaction PubMed 17786239. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm 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 transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	histone deacetylase activity Traceable author statement PubMed 12711221. Source: UniProtKB 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
Pcbp1	P60335	6	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 588

588

Histone deacetylase 9

PRO_0000114711

Regions

Region

23 – 27

5

Interaction with CTBP1

Region

136 – 154

19

Interaction with MEF2

Region

175 – 343

169

Interaction with MAPK10

Region

218 – 261

44

Interaction with ETV6 By similarity

Amino acid modifications

Modified residue

22

1

Phosphoserine By similarity

Modified residue

220

1

Phosphoserine Ref.4 Ref.5

Modified residue

240

1

Phosphoserine; by DYRK1B Ref.6

Modified residue

450

1

Phosphoserine Ref.4 Ref.5

Natural variations

Alternative sequence

177 – 178

2

Missing in isoform 3.

VSP_029173

Alternative sequence

219 – 262

44

Missing in isoform 2.

VSP_023769

Experimental info

Mutagenesis

25 – 26

2

DL → AS: Abolishes binding to CTBP1 and impairs function in transcription repression. Ref.1

Sequence conflict

120

1

R → K in AAK15027. Ref.2

Sequence conflict

120

1

R → K in AAL86358. Ref.2

Sequence conflict

136

1

R → K in AAK15027. Ref.2

Sequence conflict

136

1

R → K in AAL86358. Ref.2

Sequence conflict

388

1

N → T in AAH98187. Ref.3

Sequence conflict

523

1

N → T in AAG48332. Ref.1

Secondary structure

1

.

.

.

588

Helix Strand Turn

Details...

Helix

143 – 153

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 20, 2007. Version 2. Checksum: 4ED7FA9F02BD4621	FASTA	588	65,687
	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
	Isoform 2 (Hdrpa) [UniParc]. Checksum: 60B1203BC91D87D0	FASTA	544	60,609
	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 DDFPLRKTES SVSSSSPGSG PSSPNNGPAG 250 260 270 280 290 300 NVTENEASAL PPTPHPEQLV PQQRILIHED SMNLLSLYTS PSLPNITLGL PAVPSPLNAS 310 320 330 340 350 360 NSLKDKQKCE TQMLRQGVPL PSQYGSSIAA SSSHVHVAME GKPNSSHQAL LQHLLLKEQM 370 380 390 400 410 420 RQQKLLVAGG VPLHPQSPLA TKERISPGIR GTHKLPRHRP LNRTQSAPLP QSTLAQLVIQ 430 440 450 460 470 480 QQHQQFLEKQ KQYQQQIHMN KLLSKSIEQL KQPGSHLEEA EEELQGDQSM EDRAASKDNS 490 500 510 520 530 540 ARSDSSACVE DTLGQVGAVK VKEEPVDSDE DAQIQEMECG EQAAFMQQVI GKDLAPGFVI KVII
	Isoform 3 [UniParc]. Checksum: E92E1B8ED6AD5C99	FASTA	586	65,422
	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 RHPKLWAAHH 190 200 210 220 230 240 TSLDQSSPPL SGTSPSYKYT LPGAQDSKDD FPLRKTASEP NLKVRSRLKQ KVAERRSSPL 250 260 270 280 290 300 LRRKDGNLVT SFKKRVFEVA ESSVSSSSPG SGPSSPNNGP AGNVTENEAS ALPPTPHPEQ 310 320 330 340 350 360 LVPQQRILIH EDSMNLLSLY TSPSLPNITL GLPAVPSPLN ASNSLKDKQK CETQMLRQGV 370 380 390 400 410 420 PLPSQYGSSI AASSSHVHVA MEGKPNSSHQ ALLQHLLLKE QMRQQKLLVA GGVPLHPQSP 430 440 450 460 470 480 LATKERISPG IRGTHKLPRH RPLNRTQSAP LPQSTLAQLV IQQQHQQFLE KQKQYQQQIH 490 500 510 520 530 540 MNKLLSKSIE QLKQPGSHLE EAEEELQGDQ SMEDRAASKD NSARSDSSAC VEDTLGQVGA 550 560 570 580 VKVKEEPVDS DEDAQIQEME CGEQAAFMQQ VIGKDLAPGF VIKVII

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00153962.
IPI00874391.
IPI00875766.

RefSeq

NP_077038.2. NM_024124.3.

UniGene

Mm.310551.
Mm.483009.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TQE	X-ray	2.70	X/Y	139-158	[»]

ProteinModelPortal

Q99N13.

SMR

Q99N13. Positions 37-101.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41905N.

IntAct

Q99N13. 5 interactions.

MINT

MINT-146908.

PTM databases

PhosphoSite

Q99N13.

Proteomic databases

PaxDb

Q99N13.

PRIDE

Q99N13.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000110819; ENSMUSP00000106443; ENSMUSG00000004698.

GeneID

79221.

KEGG

mmu:79221.

UCSC

uc007nja.1. mouse.
uc007njb.1. mouse.
uc007njc.2. mouse.

Organism-specific databases

CTD

9734.

MGI

MGI:1931221. Hdac9.

Phylogenomic databases

eggNOG

COG0123.

GeneTree

ENSGT00530000062809.

HOGENOM

HOG000232065.

HOVERGEN

HBG057100.

KO

K11409.

Gene expression databases

Bgee

Q99N13.

CleanEx

MM_HDAC9.

Genevestigator

Q99N13.

GermOnline

ENSMUSG00000004698. Mus musculus.

Family and domain databases

InterPro

IPR024643. Hist_deacetylase_Gln_rich_N.
[Graphical view]

Pfam

PF12203. HDAC4_Gln. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q99N13.

ChEMBL

CHEMBL5204.

ChiTaRS

HDAC9. mouse.

EvolutionaryTrace

Q99N13.

NextBio

349885.

SOURCE

Search...

Entry information

Entry name

HDAC9_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program