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Protein

Histone acetyltransferase KAT2A

Gene

Kat2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Protein lysine acyltransferase that can act both as a acetyltransferase and succinyltransferase, depending on the context (PubMed:28424240). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (By similarity). Succinylation of histones gives a specific tag for epigenetic transcription activation (By similarity). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (By similarity). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (By similarity). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (By similarity). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:28424240). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (PubMed:25024434). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at Lys-9 (H3K9ac), leading to promote IL2 expression (PubMed:28424240). Also acetylates non-histone proteins, such as CEBPB, PLK4 and TBX5 (PubMed:17301242). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (By similarity). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (By similarity).By similarity3 Publications

Catalytic activityi

Acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine.1 Publication
Succinyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-succinyl-L-lysine.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei568Proton donor/acceptorBy similarity1
Binding sitei638Succinyl-CoABy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAcyltransferase, Transferase
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-MMU-350054 Notch-HLH transcription pathway
R-MMU-5250924 B-WICH complex positively regulates rRNA expression
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8941856 RUNX3 regulates NOTCH signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Histone acetyltransferase KAT2ACurated (EC:2.3.1.481 Publication)
Alternative name(s):
General control of amino acid synthesis protein 5-like 21 Publication
Histone acetyltransferase GCN51 Publication
Short name:
MmGCN51 Publication
Histone succinyltransferase KAT2ABy similarity (EC:2.3.1.-By similarity)
Lysine acetyltransferase 2ACurated
Gene namesi
Name:Kat2aImported
Synonyms:Gcn5l21 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1343101 Kat2a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

Lethality during embryogenesis: embryos develop normally to 7.5 days post coitum (dpc), but growth is severely retarded by 8.5 dpc and embryos fail to form dorsal mesoderm lineages, including chordamesoderm and paraxial mesoderm (PubMed:11017084). Differentiation of extra-embryonic and cardiac mesoderm is not affected (PubMed:11017084). Loss of the dorsal mesoderm lineages is due to a increased apoptosis (PubMed:11017084). Conditional knockout mice lacking Kat2a in the excitatory neurons of the adult forebrain display impaired hippocampus-dependent memory consolidation as well as impaired synaptic and nuclear plasticity (PubMed:25024434). Conditional knockout mice lacking Kat2a in T lymphocytes show defects in T-cell activation, T-cell proliferation, IL2 production and Th1/Th17 regulatory T-cell differentiation (PubMed:28424240). Th2 regulatory T-cell differentiation is not affected (PubMed:28424240).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002112032 – 830Histone acetyltransferase KAT2AAdd BLAST829

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Cross-linki721Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki752Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki784Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9JHD2
MaxQBiQ9JHD2
PaxDbiQ9JHD2
PRIDEiQ9JHD2

PTM databases

iPTMnetiQ9JHD2
PhosphoSitePlusiQ9JHD2

Expressioni

Tissue specificityi

In brain, highly expressed in the hippocampal CA1 region (at protein level) (PubMed:25024434). Also expressed in the hippocampal subregions CA3 and the dentate gyrus as well as in the cortex and prefrontal cortex (PubMed:25024434). Expressed at low level in the cerebellum (PubMed:25024434).1 Publication

Developmental stagei

Expressed uniformly throughout the embryo from 7.5 to 9.0 dpc, except in the distal allantois and developing heart. Gcn5l2 expression is down-regulated after 16.5 dpc, but is later up-regulated in specific adult tissues.1 Publication

Gene expression databases

BgeeiENSMUSG00000020918 Expressed in 292 organ(s), highest expression level in ear
ExpressionAtlasiQ9JHD2 baseline and differential
GenevisibleiQ9JHD2 MM

Interactioni

Subunit structurei

Interacts with EP300, CREBBP and ADA2 (By similarity). Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L, SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, KAT2A/GCN5L2, TAF10 and TRRAP (By similarity). Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (By similarity). The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22 (By similarity). Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity). In the complex, it probably interacts directly with KAT14, MBIP and WDR5 (By similarity). Interacts with PML (PubMed:22886304). Interacts with CEBPB (PubMed:17301242). Interacts with TACC1, TACC2 and TACC3 (By similarity). Interacts with RELA (PubMed:25024434). Interacts with NFATC2 (PubMed:28424240). Interacts with TBX5 (By similarity). Interacts with PLK4 (By similarity). Associates with the 2-oxoglutarate dehydrogenase complex (By similarity).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199867, 12 interactors
ComplexPortaliCPX-1025 GCN5-containing ATAC complex
CPX-916 TFTC histone acetylation complex
CPX-920 SAGA complex
DIPiDIP-29180N
IntActiQ9JHD2, 58 interactors
MINTiQ9JHD2
STRINGi10090.ENSMUSP00000099407

Structurei

3D structure databases

ProteinModelPortaliQ9JHD2
SMRiQ9JHD2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini496 – 649N-acetyltransferasePROSITE-ProRule annotationAdd BLAST154
Domaini738 – 808BromoPROSITE-ProRule annotationAdd BLAST71

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni572 – 574Acetyl-CoA and succinyl-CoA bindingBy similarity3
Regioni579 – 585Acetyl-CoA and succinyl-CoA bindingBy similarity7
Regioni610 – 613Acetyl-CoA and succinyl-CoA bindingBy similarity4

Domaini

Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-638 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.By similarity

Sequence similaritiesi

Keywords - Domaini

Bromodomain

Phylogenomic databases

eggNOGiKOG1472 Eukaryota
COG5076 LUCA
GeneTreeiENSGT00930000150850
HOGENOMiHOG000007151
HOVERGENiHBG051710
InParanoidiQ9JHD2
KOiK06062
OrthoDBiEOG091G03ZO
TreeFamiTF105399

Family and domain databases

Gene3Di1.20.920.10, 1 hit
InterProiView protein in InterPro
IPR016181 Acyl_CoA_acyltransferase
IPR001487 Bromodomain
IPR036427 Bromodomain-like_sf
IPR018359 Bromodomain_CS
IPR037800 GCN5
IPR016376 GCN5/PCAF
IPR000182 GNAT_dom
IPR009464 PCAF_N
PANTHERiPTHR22880:SF124 PTHR22880:SF124, 1 hit
PfamiView protein in Pfam
PF00583 Acetyltransf_1, 1 hit
PF00439 Bromodomain, 1 hit
PF06466 PCAF_N, 1 hit
PIRSFiPIRSF003048 Histone_acetylase_PCAF, 1 hit
PRINTSiPR00503 BROMODOMAIN
SMARTiView protein in SMART
SM00297 BROMO, 1 hit
SUPFAMiSSF47370 SSF47370, 1 hit
SSF55729 SSF55729, 1 hit
PROSITEiView protein in PROSITE
PS00633 BROMODOMAIN_1, 1 hit
PS50014 BROMODOMAIN_2, 1 hit
PS51186 GNAT, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q9JHD2-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAEPSQAPNP VPAAQPRPLH SPAPAPTSTP APSPASASTP APTPAPAPAP
60 70 80 90 100
AAAPAGSTGS GGAGVGSGGD PARPGLSQQQ RASQRKAQVR GLPRAKKLEK
110 120 130 140 150
LGVFSACKAN ETCKCNGWKN PKPPTAPRMD LQQPAANLSE LCRSCEHPLA
160 170 180 190 200
DHVSHLENVS EDEINRLLGM VVDVENLFMS VHKEEDTDTK QVYFYLFKLL
210 220 230 240 250
RKCILQMTRP VVEGSLGSPP FEKPNIEQGV LNFVQYKFSH LAPRERQTMF
260 270 280 290 300
ELSKMFLLCL NYWKLETPAQ FRQRSQSEDV ATYKVNYTRW LCYCHVPQSC
310 320 330 340 350
DSLPRYETTH VFGRSLLRSI FTVTRRQLLE KFRVEKDKLV PEKRTLILTH
360 370 380 390 400
FPKFLSMLEE EIYGANSPIW ESGFTMPPSE GTQLVPRPAT VSATVVPSFS
410 420 430 440 450
PSMGGGSNSS LSLDSAGTEP MPAGEKRKLP ENLTLEDAKR LRVMGDIPME
460 470 480 490 500
LVNEVMLTIT DPAAMLGPET SLLSANAARD ETARLEERRG IIEFHVIGNS
510 520 530 540 550
LTPKANRRVL LWLVGLQNVF SHQLPRMPKE YIARLVFDPK HKTLALIKDG
560 570 580 590 600
RVIGGICFRM FPTQGFTEIV FCAVTSNEQV KGYGTHLMNH LKEYHIKHSI
610 620 630 640 650
LYFLTYADEY AIGYFKKQGF SKDIKVPKSR YLGYIKDYEG ATLMECELNP
660 670 680 690 700
RIPYTELSHI IKKQKEIIKK LIERKQAQIR KVYPGLSCFK EGVRQIPVES
710 720 730 740 750
VPGIRETGWK PLGKEKGKEL KDPDQLYTTL KNLLAQIKSH PSAWPFMEPV
760 770 780 790 800
KKSEAPDYYE VIRFPIDLKT MTERLRSRYY VTRKLFVADL QRVIANCREY
810 820 830
NPPDSEYCRC ASALEKFFYF KLKEGGLIDK
Length:830
Mass (Da):93,394
Last modified:July 27, 2011 - v2
Checksum:i7993CFFEA4734174
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q6P3Z8Q6P3Z8_MOUSE
Histone acetyltransferase
Kat2a Gcn5l2
829Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti804D → N in AAF70497 (PubMed:9742083).Curated1
Sequence conflicti815E → K in AAF70497 (PubMed:9742083).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF254441 mRNA Translation: AAF70497.1
AK158079 mRNA Translation: BAE34351.1
AL591469 Genomic DNA Translation: CAM22909.1
CH466662 Genomic DNA Translation: EDL02541.1
CCDSiCCDS25433.1
RefSeqiNP_064388.2, NM_020004.5
UniGeneiMm.218837

Genome annotation databases

EnsembliENSMUST00000103118; ENSMUSP00000099407; ENSMUSG00000020918
GeneIDi14534
KEGGimmu:14534
UCSCiuc007lma.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF254441 mRNA Translation: AAF70497.1
AK158079 mRNA Translation: BAE34351.1
AL591469 Genomic DNA Translation: CAM22909.1
CH466662 Genomic DNA Translation: EDL02541.1
CCDSiCCDS25433.1
RefSeqiNP_064388.2, NM_020004.5
UniGeneiMm.218837

3D structure databases

ProteinModelPortaliQ9JHD2
SMRiQ9JHD2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199867, 12 interactors
ComplexPortaliCPX-1025 GCN5-containing ATAC complex
CPX-916 TFTC histone acetylation complex
CPX-920 SAGA complex
DIPiDIP-29180N
IntActiQ9JHD2, 58 interactors
MINTiQ9JHD2
STRINGi10090.ENSMUSP00000099407

PTM databases

iPTMnetiQ9JHD2
PhosphoSitePlusiQ9JHD2

Proteomic databases

EPDiQ9JHD2
MaxQBiQ9JHD2
PaxDbiQ9JHD2
PRIDEiQ9JHD2

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000103118; ENSMUSP00000099407; ENSMUSG00000020918
GeneIDi14534
KEGGimmu:14534
UCSCiuc007lma.2 mouse

Organism-specific databases

CTDi2648
MGIiMGI:1343101 Kat2a

Phylogenomic databases

eggNOGiKOG1472 Eukaryota
COG5076 LUCA
GeneTreeiENSGT00930000150850
HOGENOMiHOG000007151
HOVERGENiHBG051710
InParanoidiQ9JHD2
KOiK06062
OrthoDBiEOG091G03ZO
TreeFamiTF105399

Enzyme and pathway databases

ReactomeiR-MMU-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-MMU-350054 Notch-HLH transcription pathway
R-MMU-5250924 B-WICH complex positively regulates rRNA expression
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8941856 RUNX3 regulates NOTCH signaling

Miscellaneous databases

ChiTaRSiKat2a mouse
PROiPR:Q9JHD2
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020918 Expressed in 292 organ(s), highest expression level in ear
ExpressionAtlasiQ9JHD2 baseline and differential
GenevisibleiQ9JHD2 MM

Family and domain databases

Gene3Di1.20.920.10, 1 hit
InterProiView protein in InterPro
IPR016181 Acyl_CoA_acyltransferase
IPR001487 Bromodomain
IPR036427 Bromodomain-like_sf
IPR018359 Bromodomain_CS
IPR037800 GCN5
IPR016376 GCN5/PCAF
IPR000182 GNAT_dom
IPR009464 PCAF_N
PANTHERiPTHR22880:SF124 PTHR22880:SF124, 1 hit
PfamiView protein in Pfam
PF00583 Acetyltransf_1, 1 hit
PF00439 Bromodomain, 1 hit
PF06466 PCAF_N, 1 hit
PIRSFiPIRSF003048 Histone_acetylase_PCAF, 1 hit
PRINTSiPR00503 BROMODOMAIN
SMARTiView protein in SMART
SM00297 BROMO, 1 hit
SUPFAMiSSF47370 SSF47370, 1 hit
SSF55729 SSF55729, 1 hit
PROSITEiView protein in PROSITE
PS00633 BROMODOMAIN_1, 1 hit
PS50014 BROMODOMAIN_2, 1 hit
PS51186 GNAT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKAT2A_MOUSE
AccessioniPrimary (citable) accession number: Q9JHD2
Secondary accession number(s): Q3TZ59
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 155 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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