ID KAT2A_HUMAN Reviewed; 837 AA.
AC Q92830; Q8N1A2; Q9UCW1;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 3.
DT 01-MAY-2013, entry version 146.
DE RecName: Full=Histone acetyltransferase KAT2A;
DE EC=2.3.1.48;
DE AltName: Full=General control of amino acid synthesis protein 5-like 2;
DE AltName: Full=Histone acetyltransferase GCN5;
DE Short=HsGCN5;
DE AltName: Full=Lysine acetyltransferase 2A;
DE AltName: Full=STAF97;
GN Name=KAT2A; Synonyms=GCN5, GCN5L2, HGCN5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), AND CHARACTERIZATION.
RC TISSUE=Testis;
RX PubMed=8552087;
RA Candau R., Moore P.A., Wang L., Barlev N., Ying C.Y., Rosen C.A.,
RA Berger S.L.;
RT "Identification of human proteins functionally conserved with the
RT yeast putative adaptors ADA2 and GCN5.";
RL Mol. Cell. Biol. 16:593-602(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Liver;
RX PubMed=9611240; DOI=10.1093/nar/26.12.2948;
RA Smith E.R., Belote J.M., Schlitz R.L., Yang X.-J., Moore P.A.,
RA Berger S.L., Nakatani Y., Allis C.D.;
RT "Cloning of Drosophila GCN5: conserved features among metazoan GCN5
RT family members.";
RL Nucleic Acids Res. 26:2948-2954(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, Skin, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 362-837 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8684459; DOI=10.1038/382319a0;
RA Yang X.-J., Ogryzko V.V., Nishikawa J., Howard B.H., Nakatani Y.;
RT "A p300/CBP-associated factor that competes with the adenoviral
RT oncoprotein E1A.";
RL Nature 382:319-324(1996).
RN [6]
RP MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE
RP STAGA COMPLEX WITH SUPT3H; KIAA0764; TAF5L; TAF6L; TRRAP; TADA3L;
RP TAF10; TAF12 AND TAF9.
RX PubMed=11564863; DOI=10.1128/MCB.21.20.6782-6795.2001;
RA Martinez E., Palhan V.B., Tjernberg A., Lymar E.S., Gamper A.M.,
RA Kundu T.K., Chait B.T., Roeder R.G.;
RT "Human STAGA complex is a chromatin-acetylating transcription
RT coactivator that interacts with pre-mRNA splicing and DNA damage-
RT binding factors in vivo.";
RL Mol. Cell. Biol. 21:6782-6795(2001).
RN [7]
RP IDENTIFICATION IN THE TFTC-HAT COMPLEX WITH TAF5L; TAF6L; TADA3L;
RP SUPT3H; TAF2; TAF4; TAF5; TRRAP AND TAF10.
RX PubMed=10373431; DOI=10.1074/jbc.274.26.18285;
RA Brand M., Yamamoto K., Staub A., Tora L.;
RT "Identification of TATA-binding protein-free TAFII-containing complex
RT subunits suggests a role in nucleosome acetylation and signal
RT transduction.";
RL J. Biol. Chem. 274:18285-18289(1999).
RN [8]
RP INTERACTION WITH TRRAP.
RX PubMed=10611234; DOI=10.1128/MCB.20.2.556-562.2000;
RA McMahon S.B., Wood M.A., Cole M.D.;
RT "The essential cofactor TRRAP recruits the histone acetyltransferase
RT hGCN5 to c-Myc.";
RL Mol. Cell. Biol. 20:556-562(2000).
RN [9]
RP INTERACTION WITH HIV-1 TAT.
RX PubMed=11384967; DOI=10.1074/jbc.M101385200;
RA Col E., Caron C., Seigneurin-Berny D., Gracia J., Favier A.,
RA Khochbin S.;
RT "The histone acetyltransferase, hGCN5, interacts with and acetylates
RT the HIV transactivator, Tat.";
RL J. Biol. Chem. 276:28179-28184(2001).
RN [10]
RP INTERACTION WITH TAF3.
RX PubMed=11438666; DOI=10.1128/MCB.21.15.5109-5121.2001;
RA Gangloff Y.G., Pointud J.-C., Thuault S., Carre L., Romier C.,
RA Muratoglu S., Brand M., Tora L., Couderc J.-L., Davidson I.;
RT "The TFIID components human TAFII140 and Drosophila BIP2 (TAFII155)
RT are novel metazoan homologues of yeast TAFII47 containing a histone
RT fold and a PHD finger.";
RL Mol. Cell. Biol. 21:5109-5121(2001).
RN [11]
RP INTERACTION WITH TACC1; TACC2 AND TACC3.
RX PubMed=14767476; DOI=10.1038/sj.onc.1207424;
RA Gangisetty O., Lauffart B., Sondarva G.V., Chelsea D.M., Still I.H.;
RT "The transforming acidic coiled coil proteins interact with nuclear
RT histone acetyltransferases.";
RL Oncogene 23:2559-2563(2004).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP IDENTIFICATION IN STAGA COMPLEX.
RX PubMed=18206972; DOI=10.1016/j.molcel.2007.12.011;
RA Zhao Y., Lang G., Ito S., Bonnet J., Metzger E., Sawatsubashi S.,
RA Suzuki E., Le Guezennec X., Stunnenberg H.G., Krasnov A.,
RA Georgieva S.G., Schuele R., Takeyama K., Kato S., Tora L., Devys D.;
RT "A TFTC/STAGA module mediates histone H2A and H2B deubiquitination,
RT coactivates nuclear receptors, and counteracts heterochromatin
RT silencing.";
RL Mol. Cell 29:92-101(2008).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN ATAC COMPLEX.
RX PubMed=19103755; DOI=10.1128/MCB.01599-08;
RA Guelman S., Kozuka K., Mao Y., Pham V., Solloway M.J., Wang J., Wu J.,
RA Lill J.R., Zha J.;
RT "The double-histone-acetyltransferase complex ATAC is essential for
RT mammalian development.";
RL Mol. Cell. Biol. 29:1176-1188(2009).
RN [15]
RP STRUCTURE BY NMR OF 730-832.
RX PubMed=11090279; DOI=10.1006/jmbi.2000.4207;
RA Hudson B.P., Martinez-Yamout M.A., Dyson H.J., Wright P.E.;
RT "Solution structure and acetyl-lysine binding activity of the GCN5
RT bromodomain.";
RL J. Mol. Biol. 304:355-370(2000).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 729-837.
RX PubMed=22464331; DOI=10.1016/j.cell.2012.02.013;
RA Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P.,
RA Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T.,
RA Gingras A.C., Arrowsmith C.H., Knapp S.;
RT "Histone recognition and large-scale structural analysis of the human
RT bromodomain family.";
RL Cell 149:214-231(2012).
CC -!- FUNCTION: Functions as a histone acetyltransferase (HAT) to
CC promote transcriptional activation. Acetylation of histones gives
CC a specific tag for epigenetic transcription activation. Has
CC significant histone acetyltransferase activity with core histones,
CC but not with nucleosome core particles. In case of HIV-1
CC infection, it is recruited by the viral protein Tat. Regulates
CC Tat's transactivating activity and may help inducing chromatin
CC remodeling of proviral genes. Component of the ATAC complex, a
CC complex with histone acetyltransferase activity on histones H3 and
CC H4.
CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl-
CC [histone].
CC -!- SUBUNIT: Interacts with EP300, CREBBP and ADA2. Component of the
CC TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L,
CC SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100,
CC KAT2A/GCN5L2, TAF10 and TRRAP. Interacts with TRRAP. Component of
CC the STAGA transcription coactivator-HAT complex, at least composed
CC of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10,
CC TAF12, TRRAP and TAF9. The STAGA core complex is associated with a
CC subcomplex required for histone deubiquitination composed of
CC ATXN7L3, ENY2 and USP22. Interacts with and acetylates HIV-1 Tat.
CC Component of the ADA2A-containing complex (ATAC), composed of
CC CSRP2BP, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101
CC and DR1. In the complex, it probably interacts directly with
CC CSRP2BP, MBIP and WDR5. Interacts with PML (By similarity).
CC -!- INTERACTION:
CC O75717:WDHD1; NbExp=5; IntAct=EBI-477622, EBI-3951691;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=GCN5-L;
CC IsoId=Q92830-1; Sequence=Displayed;
CC Name=2; Synonyms=GCN5-S;
CC IsoId=Q92830-2; Sequence=VSP_000556;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, with most
CC abundant expression in ovary.
CC -!- SIMILARITY: Belongs to the GCN5 family.
CC -!- SIMILARITY: Contains 1 bromo domain.
CC -!- SIMILARITY: Contains 1 N-acetyltransferase domain.
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DR EMBL; AF029777; AAC39769.1; -; mRNA.
DR EMBL; CH471152; EAW60803.1; -; Genomic_DNA.
DR EMBL; BC032743; AAH32743.1; -; mRNA.
DR EMBL; BC039907; AAH39907.1; -; mRNA.
DR EMBL; BC105977; AAI05978.1; -; mRNA.
DR EMBL; U57316; AAC50641.1; -; Genomic_DNA.
DR IPI; IPI00221199; -.
DR IPI; IPI00306871; -.
DR PIR; S71789; S71789.
DR RefSeq; NP_066564.2; NM_021078.2.
DR UniGene; Hs.463045; -.
DR PDB; 1F68; NMR; -; A=731-832.
DR PDB; 1Z4R; X-ray; 1.74 A; A=497-662.
DR PDB; 3D7C; X-ray; 2.06 A; A/B=729-837.
DR PDBsum; 1F68; -.
DR PDBsum; 1Z4R; -.
DR PDBsum; 3D7C; -.
DR ProteinModelPortal; Q92830; -.
DR DIP; DIP-28146N; -.
DR IntAct; Q92830; 21.
DR MINT; MINT-199927; -.
DR STRING; 9606.ENSP00000225916; -.
DR PhosphoSite; Q92830; -.
DR DMDM; 209572743; -.
DR PaxDb; Q92830; -.
DR PRIDE; Q92830; -.
DR Ensembl; ENST00000225916; ENSP00000225916; ENSG00000108773.
DR Ensembl; ENST00000564173; ENSP00000456712; ENSG00000259958.
DR GeneID; 2648; -.
DR KEGG; hsa:2648; -.
DR UCSC; uc002hyx.2; human.
DR CTD; 2648; -.
DR GeneCards; GC17M040265; -.
DR HGNC; HGNC:4201; KAT2A.
DR HPA; HPA048958; -.
DR MIM; 602301; gene.
DR neXtProt; NX_Q92830; -.
DR PharmGKB; PA162392664; -.
DR eggNOG; COG5076; -.
DR HOGENOM; HOG000007151; -.
DR InParanoid; Q92830; -.
DR KO; K06062; -.
DR OMA; GENSPIW; -.
DR OrthoDB; EOG4F1X2G; -.
DR PhylomeDB; Q92830; -.
DR Pathway_Interaction_DB; smad2_3nuclearpathway; Regulation of nuclear SMAD2/3 signaling.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_2155; NICD traffics to nucleus.
DR Reactome; REACT_71; Gene Expression.
DR ChEMBL; CHEMBL5501; -.
DR ChiTaRS; KAT2A; human.
DR EvolutionaryTrace; Q92830; -.
DR GenomeRNAi; 2648; -.
DR NextBio; 10450; -.
DR Bgee; Q92830; -.
DR CleanEx; HS_KAT2A; -.
DR Genevestigator; Q92830; -.
DR GermOnline; ENSG00000108773; Homo sapiens.
DR GO; GO:0005671; C:Ada2/Gcn5/Ada3 transcription activator complex; IDA:BHF-UCL.
DR GO; GO:0072686; C:mitotic spindle; IEA:Compara.
DR GO; GO:0030914; C:STAGA complex; IDA:UniProtKB.
DR GO; GO:0033276; C:transcription factor TFTC complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Compara.
DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0043997; F:histone acetyltransferase activity (H4-K12 specific); IEA:Compara.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IEA:Compara.
DR GO; GO:0006338; P:chromatin remodeling; TAS:ProtInc.
DR GO; GO:0016578; P:histone deubiquitination; IDA:UniProtKB.
DR GO; GO:0044154; P:histone H3-K14 acetylation; IEA:Compara.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Compara.
DR GO; GO:0022037; P:metencephalon development; IEA:Compara.
DR GO; GO:0030901; P:midbrain development; IEA:Compara.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Compara.
DR GO; GO:0001843; P:neural tube closure; IEA:Compara.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Compara.
DR GO; GO:0031647; P:regulation of protein stability; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0001756; P:somitogenesis; IEA:Compara.
DR GO; GO:0021537; P:telencephalon development; IEA:Compara.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.
DR Gene3D; 1.20.920.10; -; 1.
DR Gene3D; 3.40.630.30; -; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR016376; Hist_acetylase_PCAF.
DR InterPro; IPR009464; PCAF_N.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR Pfam; PF00439; Bromodomain; 1.
DR Pfam; PF06466; PCAF_N; 1.
DR PIRSF; PIRSF003048; Histone_acetylase_PCAF; 1.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00297; BROMO; 1.
DR SUPFAM; SSF55729; Acyl_CoA_acyltransferase; 1.
DR SUPFAM; SSF47370; Bromodomain; 1.
DR PROSITE; PS00633; BROMODOMAIN_1; 1.
DR PROSITE; PS50014; BROMODOMAIN_2; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Bromodomain; Complete proteome;
KW Host-virus interaction; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1 837 Histone acetyltransferase KAT2A.
FT /FTId=PRO_0000211202.
FT DOMAIN 503 656 N-acetyltransferase.
FT DOMAIN 745 815 Bromo.
FT VAR_SEQ 1 410 Missing (in isoform 2).
FT /FTId=VSP_000556.
FT CONFLICT 116 116 E -> G (in Ref. 1; AAC39769).
FT CONFLICT 134 134 M -> I (in Ref. 1; AAC39769).
FT CONFLICT 269 269 K -> E (in Ref. 1; AAC39769).
FT STRAND 498 504
FT HELIX 514 530
FT HELIX 536 543
FT STRAND 549 555
FT STRAND 558 568
FT TURN 569 572
FT STRAND 573 581
FT HELIX 583 585
FT STRAND 587 589
FT HELIX 590 604
FT STRAND 609 614
FT HELIX 616 618
FT HELIX 619 624
FT STRAND 627 629
FT HELIX 635 638
FT TURN 639 641
FT STRAND 649 654
FT HELIX 730 746
FT HELIX 748 753
FT TURN 759 761
FT HELIX 765 768
FT HELIX 775 783
FT HELIX 790 807
FT HELIX 813 831
SQ SEQUENCE 837 AA; 93926 MW; 728CC8ACF08600EA CRC64;
MAEPSQAPTP APAAQPRPLQ SPAPAPTPTP APSPASAPIP TPTPAPAPAP AAAPAGSTGT
GGPGVGSGGA GSGGDPARPG LSQQQRASQR KAQVRGLPRA KKLEKLGVFS ACKANETCKC
NGWKNPKPPT APRMDLQQPA ANLSELCRSC EHPLADHVSH LENVSEDEIN RLLGMVVDVE
NLFMSVHKEE DTDTKQVYFY LFKLLRKCIL QMTRPVVEGS LGSPPFEKPN IEQGVLNFVQ
YKFSHLAPRE RQTMFELSKM FLLCLNYWKL ETPAQFRQRS QAEDVATYKV NYTRWLCYCH
VPQSCDSLPR YETTHVFGRS LLRSIFTVTR RQLLEKFRVE KDKLVPEKRT LILTHFPKFL
SMLEEEIYGA NSPIWESGFT MPPSEGTQLV PRPASVSAAV VPSTPIFSPS MGGGSNSSLS
LDSAGAEPMP GEKRTLPENL TLEDAKRLRV MGDIPMELVN EVMLTITDPA AMLGPETSLL
SANAARDETA RLEERRGIIE FHVIGNSLTP KANRRVLLWL VGLQNVFSHQ LPRMPKEYIA
RLVFDPKHKT LALIKDGRVI GGICFRMFPT QGFTEIVFCA VTSNEQVKGY GTHLMNHLKE
YHIKHNILYF LTYADEYAIG YFKKQGFSKD IKVPKSRYLG YIKDYEGATL MECELNPRIP
YTELSHIIKK QKEIIKKLIE RKQAQIRKVY PGLSCFKEGV RQIPVESVPG IRETGWKPLG
KEKGKELKDP DQLYTTLKNL LAQIKSHPSA WPFMEPVKKS EAPDYYEVIR FPIDLKTMTE
RLRSRYYVTR KLFVADLQRV IANCREYNPP DSEYCRCASA LEKFFYFKLK EGGLIDK
//
