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Protein

Histone acetyltransferase KAT2A

Gene

KAT2A

Organism
Homo sapiens (Human)
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:29211711). 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 (PubMed:29211711). Succinylation of histones gives a specific tag for epigenetic transcription activation (PubMed:29211711). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (PubMed:29211711). In different complexes, functions either as a acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (PubMed:17301242, PubMed:19103755, PubMed:29211711). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (PubMed:17301242, PubMed:19103755). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:17301242, PubMed:19103755, PubMed:29211711). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (By similarity). 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 (By similarity). Also acetylates non-histone proteins, such as CEBPB, PLK4 and TBX5 (PubMed:17301242, PubMed:29174768, PubMed:27796307). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307).By similarity5 Publications
(Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.1 Publication

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.1 Publication

Kineticsi

  1. KM=0.83 µM for acetyl-CoA1 Publication
  2. KM=0.36 µM for succinyl-CoA1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei575Proton donor/acceptor1 Publication1
    Binding sitei645Succinyl-CoACombined sources1 Publication1

    GO - Molecular functioni

    • chromatin binding Source: UniProtKB
    • H3 histone acetyltransferase activity Source: BHF-UCL
    • histone acetyltransferase activity Source: UniProtKB
    • histone acetyltransferase activity (H4-K12 specific) Source: Ensembl
    • histone deacetylase binding Source: UniProtKB
    • histone succinyltransferase activity Source: UniProtKB
    • peptide-lysine-N-acetyltransferase activity Source: UniProtKB
    • protein phosphatase binding Source: Ensembl
    • thiol-dependent ubiquitinyl hydrolase activity Source: Reactome
    • transcription coactivator activity Source: UniProtKB
    • transcription factor binding Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionAcyltransferase, Transferase
    Biological processHost-virus interaction, Transcription, Transcription regulation

    Enzyme and pathway databases

    BRENDAi2.3.1.48 2681
    ReactomeiR-HSA-1912408 Pre-NOTCH Transcription and Translation
    R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
    R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
    R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
    R-HSA-3214847 HATs acetylate histones
    R-HSA-350054 Notch-HLH transcription pathway
    R-HSA-5250924 B-WICH complex positively regulates rRNA expression
    R-HSA-5689880 Ub-specific processing proteases
    R-HSA-73762 RNA Polymerase I Transcription Initiation
    R-HSA-8941856 RUNX3 regulates NOTCH signaling
    R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription
    SignaLinkiQ92830
    SIGNORiQ92830

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Histone acetyltransferase KAT2A (EC:2.3.1.481 Publication)
    Alternative name(s):
    General control of amino acid synthesis protein 5-like 2By similarity
    Histone acetyltransferase GCN52 Publications
    Short name:
    hGCN52 Publications
    Histone succinyltransferase KAT2ACurated (EC:2.3.1.-1 Publication)
    Lysine acetyltransferase 2ACurated
    STAF971 Publication
    Gene namesi
    Name:KAT2AImported
    Synonyms:GCN51 Publication, GCN5L2By similarity
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000108773.10
    HGNCiHGNC:4201 KAT2A
    MIMi602301 gene
    neXtProtiNX_Q92830

    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

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi645Y → A: Reduced histone succinylation without affecting histone acetylation. Reduced gene expression. 1 Publication1

    Organism-specific databases

    DisGeNETi2648
    OpenTargetsiENSG00000108773
    PharmGKBiPA162392664

    Chemistry databases

    ChEMBLiCHEMBL5501
    DrugBankiDB01992 Coenzyme A

    Polymorphism and mutation databases

    BioMutaiKAT2A
    DMDMi209572743

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources
    ChainiPRO_00002112022 – 837Histone acetyltransferase KAT2AAdd BLAST836

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineCombined sources1
    Cross-linki728Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
    Cross-linki759Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
    Cross-linki791Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

    Keywords - PTMi

    Acetylation, Isopeptide bond, Ubl conjugation

    Proteomic databases

    EPDiQ92830
    MaxQBiQ92830
    PaxDbiQ92830
    PeptideAtlasiQ92830
    PRIDEiQ92830

    PTM databases

    iPTMnetiQ92830
    PhosphoSitePlusiQ92830

    Expressioni

    Tissue specificityi

    Expressed in all tissues tested, with most abundant expression in ovary.

    Gene expression databases

    BgeeiENSG00000108773
    CleanExiHS_KAT2A
    ExpressionAtlasiQ92830 baseline and differential
    GenevisibleiQ92830 HS

    Organism-specific databases

    HPAiHPA048958

    Interactioni

    Subunit structurei

    Interacts with EP300, CREBBP and ADA2. 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 (PubMed:10373431, PubMed:10611234, PubMed:11438666). Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (PubMed:18206972). The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22 (PubMed:18206972). Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (PubMed:19103755). In the complex, it probably interacts directly with KAT14, MBIP and WDR5 (PubMed:19103755). Interacts with PML (By similarity). Interacts with CEBPB (PubMed:17301242). Interacts with TACC1, TACC2 and TACC3 (PubMed:14767476). Interacts with RELA (By similarity). Interacts with NFATC2 (By similarity). Interacts with TBX5 (PubMed:29174768). Interacts with PLK4 (PubMed:27796307). Associates with the 2-oxoglutarate dehydrogenase complex (PubMed:29211711).By similarity10 Publications
    (Microbial infection) Interacts with and acetylates HIV-1 Tat.1 Publication

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • histone deacetylase binding Source: UniProtKB
    • protein phosphatase binding Source: Ensembl
    • transcription factor binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi108918114 interactors.
    CORUMiQ92830
    DIPiDIP-28146N
    IntActiQ92830 38 interactors.
    MINTiQ92830
    STRINGi9606.ENSP00000225916

    Chemistry databases

    BindingDBiQ92830

    Structurei

    Secondary structure

    1837
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi498 – 504Combined sources7
    Helixi514 – 530Combined sources17
    Helixi536 – 543Combined sources8
    Beta strandi549 – 555Combined sources7
    Beta strandi558 – 568Combined sources11
    Turni569 – 572Combined sources4
    Beta strandi573 – 581Combined sources9
    Helixi583 – 585Combined sources3
    Beta strandi587 – 589Combined sources3
    Helixi590 – 604Combined sources15
    Beta strandi609 – 614Combined sources6
    Helixi616 – 618Combined sources3
    Helixi619 – 624Combined sources6
    Beta strandi627 – 629Combined sources3
    Helixi635 – 638Combined sources4
    Turni639 – 641Combined sources3
    Beta strandi649 – 654Combined sources6
    Helixi730 – 746Combined sources17
    Helixi748 – 753Combined sources6
    Turni759 – 761Combined sources3
    Helixi765 – 768Combined sources4
    Helixi775 – 783Combined sources9
    Helixi790 – 807Combined sources18
    Beta strandi810 – 812Combined sources3
    Helixi813 – 831Combined sources19

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1F68NMR-A730-832[»]
    1Z4RX-ray1.74A497-662[»]
    3D7CX-ray2.06A/B729-837[»]
    5H84X-ray2.00A497-662[»]
    5H86X-ray2.08A497-662[»]
    5MLJX-ray1.80A/B729-837[»]
    5TRLX-ray2.30A/B/C/D/E/F/G/H497-662[»]
    5TRMX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X497-662[»]
    ProteinModelPortaliQ92830
    SMRiQ92830
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ92830

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini503 – 656N-acetyltransferasePROSITE-ProRule annotationAdd BLAST154
    Domaini745 – 815BromoPROSITE-ProRule annotationAdd BLAST71

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni579 – 581Acetyl-CoA and succinyl-CoA bindingCombined sources2 Publications3
    Regioni586 – 592Acetyl-CoA and succinyl-CoA bindingCombined sources2 Publications7
    Regioni617 – 620Acetyl-CoA and succinyl-CoA bindingCombined sources2 Publications4
    Regioni639 – 648Loop 31 Publication10

    Domaini

    Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-645 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.1 Publication

    Sequence similaritiesi

    Keywords - Domaini

    Bromodomain

    Phylogenomic databases

    eggNOGiKOG1472 Eukaryota
    COG5076 LUCA
    GeneTreeiENSGT00760000119099
    HOGENOMiHOG000007151
    InParanoidiQ92830
    KOiK06062
    OMAiNHLKDYS
    OrthoDBiEOG091G03ZO
    PhylomeDBiQ92830
    TreeFamiTF105399

    Family and domain databases

    Gene3Di1.20.920.101 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

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q92830-1) [UniParc]FASTAAdd to basket
    Also known as: GCN5-L

    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.

    « Hide

            10         20         30         40         50
    MAEPSQAPTP APAAQPRPLQ SPAPAPTPTP APSPASAPIP TPTPAPAPAP
    60 70 80 90 100
    AAAPAGSTGT GGPGVGSGGA GSGGDPARPG LSQQQRASQR KAQVRGLPRA
    110 120 130 140 150
    KKLEKLGVFS ACKANETCKC NGWKNPKPPT APRMDLQQPA ANLSELCRSC
    160 170 180 190 200
    EHPLADHVSH LENVSEDEIN RLLGMVVDVE NLFMSVHKEE DTDTKQVYFY
    210 220 230 240 250
    LFKLLRKCIL QMTRPVVEGS LGSPPFEKPN IEQGVLNFVQ YKFSHLAPRE
    260 270 280 290 300
    RQTMFELSKM FLLCLNYWKL ETPAQFRQRS QAEDVATYKV NYTRWLCYCH
    310 320 330 340 350
    VPQSCDSLPR YETTHVFGRS LLRSIFTVTR RQLLEKFRVE KDKLVPEKRT
    360 370 380 390 400
    LILTHFPKFL SMLEEEIYGA NSPIWESGFT MPPSEGTQLV PRPASVSAAV
    410 420 430 440 450
    VPSTPIFSPS MGGGSNSSLS LDSAGAEPMP GEKRTLPENL TLEDAKRLRV
    460 470 480 490 500
    MGDIPMELVN EVMLTITDPA AMLGPETSLL SANAARDETA RLEERRGIIE
    510 520 530 540 550
    FHVIGNSLTP KANRRVLLWL VGLQNVFSHQ LPRMPKEYIA RLVFDPKHKT
    560 570 580 590 600
    LALIKDGRVI GGICFRMFPT QGFTEIVFCA VTSNEQVKGY GTHLMNHLKE
    610 620 630 640 650
    YHIKHNILYF LTYADEYAIG YFKKQGFSKD IKVPKSRYLG YIKDYEGATL
    660 670 680 690 700
    MECELNPRIP YTELSHIIKK QKEIIKKLIE RKQAQIRKVY PGLSCFKEGV
    710 720 730 740 750
    RQIPVESVPG IRETGWKPLG KEKGKELKDP DQLYTTLKNL LAQIKSHPSA
    760 770 780 790 800
    WPFMEPVKKS EAPDYYEVIR FPIDLKTMTE RLRSRYYVTR KLFVADLQRV
    810 820 830
    IANCREYNPP DSEYCRCASA LEKFFYFKLK EGGLIDK
    Length:837
    Mass (Da):93,926
    Last modified:October 14, 2008 - v3
    Checksum:i728CC8ACF08600EA
    GO
    Isoform 2 (identifier: Q92830-2) [UniParc]FASTAAdd to basket
    Also known as: GCN5-S

    The sequence of this isoform differs from the canonical sequence as follows:
         1-410: Missing.

    Show »
    Length:427
    Mass (Da):48,921
    Checksum:iA6EAE20DB0B49ADC
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti116E → G in AAC39769 (PubMed:8552087).Curated1
    Sequence conflicti134M → I in AAC39769 (PubMed:8552087).Curated1
    Sequence conflicti269K → E in AAC39769 (PubMed:8552087).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0005561 – 410Missing in isoform 2. CuratedAdd BLAST410

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF029777 mRNA Translation: AAC39769.1
    CH471152 Genomic DNA Translation: EAW60803.1
    BC032743 mRNA Translation: AAH32743.1
    BC039907 mRNA Translation: AAH39907.1
    BC105977 mRNA Translation: AAI05978.1
    U57316 Genomic DNA Translation: AAC50641.1
    CCDSiCCDS11417.1 [Q92830-1]
    PIRiS71789
    RefSeqiNP_066564.2, NM_021078.2 [Q92830-1]
    XP_016879937.1, XM_017024448.1
    UniGeneiHs.463045

    Genome annotation databases

    EnsembliENST00000225916; ENSP00000225916; ENSG00000108773 [Q92830-1]
    GeneIDi2648
    KEGGihsa:2648
    UCSCiuc002hyx.3 human [Q92830-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiKAT2A_HUMAN
    AccessioniPrimary (citable) accession number: Q92830
    Secondary accession number(s): Q8N1A2, Q9UCW1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: October 14, 2008
    Last modified: April 25, 2018
    This is version 196 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome