KAT2A_DANRE
ID KAT2A_DANRE Reviewed; 795 AA.
AC A0A0R4IXF6; A0A0R4IN10; Q1L672;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Histone acetyltransferase KAT2A {ECO:0000250|UniProtKB:Q92830};
DE EC=2.3.1.48 {ECO:0000250|UniProtKB:Q92830};
DE AltName: Full=Histone glutaryltransferase KAT2A {ECO:0000305};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q92830};
DE AltName: Full=Histone succinyltransferase KAT2A {ECO:0000250|UniProtKB:Q92830};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q92830};
DE AltName: Full=Lysine acetyltransferase 2A {ECO:0000303|PubMed:29174768};
GN Name=kat2a {ECO:0000303|PubMed:29174768,
GN ECO:0000312|ZFIN:ZDB-GENE-080403-11};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 526-715.
RX PubMed=17997606; DOI=10.1371/journal.pgen.0030188;
RA Bertrand S., Thisse B., Tavares R., Sachs L., Chaumot A., Bardet P.-L.,
RA Escriva H., Duffraisse M., Marchand O., Safi R., Thisse C., Laudet V.;
RT "Unexpected novel relational links uncovered by extensive developmental
RT profiling of nuclear receptor expression.";
RL PLoS Genet. 3:E188-E188(2007).
RN [3]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=29174768; DOI=10.1016/j.yjmcc.2017.11.013;
RA Ghosh T.K., Aparicio-Sanchez J.J., Buxton S., Ketley A., Mohamed T.,
RA Rutland C.S., Loughna S., Brook J.D.;
RT "Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb
RT development.";
RL J. Mol. Cell. Cardiol. 114:185-198(2017).
RN [4]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=30424580; DOI=10.3390/jdb6040027;
RA Sen R., Pezoa S.A., Carpio Shull L., Hernandez-Lagunas L., Niswander L.A.,
RA Artinger K.B.;
RT "Kat2a and Kat2b acetyltransferase activity regulates craniofacial
RT cartilage and bone differentiation in zebrafish and mice.";
RL J. Dev. Biol. 6:0-0(2018).
CC -!- FUNCTION: Protein lysine acyltransferase that can act as a
CC acetyltransferase, glutaryltransferase or succinyltransferase,
CC depending on the context (By similarity). Acts as a histone lysine
CC succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79'
CC (H3K79succ), with a maximum frequency around the transcription start
CC sites of genes (By similarity). Succinylation of histones gives a
CC specific tag for epigenetic transcription activation (By similarity).
CC Association with the 2-oxoglutarate dehydrogenase complex, which
CC provides succinyl-CoA, is required for histone succinylation (By
CC similarity). In different complexes, functions either as an
CC acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and
CC ATAC complexes, acts as a histone acetyltransferase (By similarity).
CC Has significant histone acetyltransferase activity with core histones,
CC but not with nucleosome core particles (By similarity). Acetylation of
CC histones gives a specific tag for epigenetic transcription activation
CC (By similarity). Also acetylates non-histone proteins, such as tbx5
CC (PubMed:29174768). Involved in heart and limb development by mediating
CC acetylation of tbx5 (PubMed:29174768). Together with kat2b, required
CC for growth and differentiation of craniofacial cartilage and bone by
CC regulating acetylation of histone H3 at 'Lys-9' (H3K9ac)
CC (PubMed:30424580). Also acts as a histone glutaryltransferase:
CC catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark
CC that destabilizes nucleosomes by promoting dissociation of the H2A-H2B
CC dimers from nucleosomes (By similarity). {ECO:0000250|UniProtKB:Q92830,
CC ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:30424580}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48;
CC Evidence={ECO:0000250|UniProtKB:Q92830};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[histone] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[histone]; Xref=Rhea:RHEA:21992, Rhea:RHEA-COMP:9845,
CC Rhea:RHEA-COMP:11338, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48;
CC Evidence={ECO:0000250|UniProtKB:Q92830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993;
CC Evidence={ECO:0000250|UniProtKB:Q92830};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + succinyl-CoA = CoA + H(+) + N(6)-succinyl-
CC L-lysyl-[protein]; Xref=Rhea:RHEA:16261, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:11877, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:87830;
CC Evidence={ECO:0000250|UniProtKB:Q92830};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutaryl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-glutaryl-
CC L-lysyl-[protein]; Xref=Rhea:RHEA:18009, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:11875, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57378, ChEBI:CHEBI:87828;
CC Evidence={ECO:0000250|UniProtKB:Q92830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18010;
CC Evidence={ECO:0000250|UniProtKB:Q92830};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q92830}.
CC Chromosome {ECO:0000250|UniProtKB:Q92830}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q92830}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed throughout the anterior head
CC region, including the central nervous system, the eye and branchial
CC arches at 24 hours post fertilization (hpf). Expressed strongly in the
CC brain region. By 40-48 hpf, expression remains strongly expressed in
CC the head region but is reduced throughout the rest of the embryo
CC (PubMed:30424580). Expressed in the heart and tail regions throughout
CC developmental stages (PubMed:29174768). {ECO:0000269|PubMed:29174768,
CC ECO:0000269|PubMed:30424580}.
CC -!- DOMAIN: Loop3 is required for substrate specificity and adopts
CC different structural conformations in succinyl-CoA-bound and acetyl-
CC CoA-bound forms. Tyr-603 has an important role in the selective binding
CC of succinyl-CoA over acetyl-CoA. {ECO:0000250|UniProtKB:Q92830}.
CC -!- DISRUPTION PHENOTYPE: Craniofacial cartilage and bone defects,
CC characterized by shortening and hypoplastic nature of the cartilage
CC elements and disruption of the posterior ceratobranchial cartilages
CC (PubMed:30424580). Morpholino knockdown of kat2a and kat2b leads to
CC impaired heart and limb development. Abnormal fin development is also
CC observed (PubMed:29174768). {ECO:0000269|PubMed:29174768,
CC ECO:0000269|PubMed:30424580}.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. GCN5 subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX005093; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FO818663; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DQ017634; AAY85289.1; -; mRNA.
DR RefSeq; XP_009297593.1; XM_009299318.2.
DR AlphaFoldDB; A0A0R4IXF6; -.
DR SMR; A0A0R4IXF6; -.
DR STRING; 7955.ENSDARP00000011795; -.
DR PaxDb; A0A0R4IXF6; -.
DR Ensembl; ENSDART00000157682; ENSDARP00000141597; ENSDARG00000104734.
DR GeneID; 555517; -.
DR KEGG; dre:555517; -.
DR CTD; 2648; -.
DR ZFIN; ZDB-GENE-080403-11; kat2a.
DR eggNOG; KOG1472; Eukaryota.
DR GeneTree; ENSGT00940000158799; -.
DR OMA; NHLKDYS; -.
DR OrthoDB; 349249at2759; -.
DR Reactome; R-DRE-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR Reactome; R-DRE-8941856; RUNX3 regulates NOTCH signaling.
DR PRO; PR:A0A0R4IXF6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000104734; Expressed in blastula and 28 other tissues.
DR ExpressionAtlas; A0A0R4IXF6; baseline.
DR GO; GO:0140672; C:ATAC complex; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0000123; C:histone acetyltransferase complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0004402; F:histone acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0106229; F:histone glutaryltransferase activity; ISS:UniProtKB.
DR GO; GO:0106078; F:histone succinyltransferase activity; ISS:UniProtKB.
DR GO; GO:0061733; F:peptide-lysine-N-acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; IMP:ZFIN.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0016573; P:histone acetylation; IMP:UniProtKB.
DR GO; GO:0043966; P:histone H3 acetylation; ISS:UniProtKB.
DR GO; GO:0044154; P:histone H3-K14 acetylation; IBA:GO_Central.
DR GO; GO:0106077; P:histone succinylation; ISS:UniProtKB.
DR GO; GO:0018393; P:internal peptidyl-lysine acetylation; ISS:UniProtKB.
DR GO; GO:0060173; P:limb development; IMP:UniProtKB.
DR GO; GO:0007616; P:long-term memory; ISS:UniProtKB.
DR GO; GO:0106227; P:peptidyl-lysine glutarylation; ISS:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:1903010; P:regulation of bone development; IMP:UniProtKB.
DR GO; GO:0061035; P:regulation of cartilage development; IMP:UniProtKB.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0050863; P:regulation of T cell activation; ISS:UniProtKB.
DR Gene3D; 1.20.920.10; -; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR037800; GCN5.
DR InterPro; IPR016376; GCN5/PCAF.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR009464; PCAF_N.
DR PANTHER; PTHR45750; PTHR45750; 1.
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; SSF47370; SSF47370; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS00633; BROMODOMAIN_1; 1.
DR PROSITE; PS50014; BROMODOMAIN_2; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Bromodomain; Chromosome; Cytoplasm; Cytoskeleton; Nucleus;
KW Reference proteome; Transcription; Transcription regulation; Transferase.
FT CHAIN 1..795
FT /note="Histone acetyltransferase KAT2A"
FT /id="PRO_0000443447"
FT DOMAIN 461..614
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT DOMAIN 703..773
FT /note="Bromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 597..606
FT /note="Loop 3"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT COMPBIAS 8..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 533
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT BINDING 537..539
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT BINDING 537..539
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT BINDING 544..550
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT BINDING 544..550
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT BINDING 575
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT BINDING 575
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000250|UniProtKB:Q92830"
FT CONFLICT 712..713
FT /note="ME -> LH (in Ref. 2; AAY85289)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 795 AA; 90624 MW; F2081631E5391B92 CRC64;
MADPAAQSSA QPRLQQAQSS GPTGSNSNPG AGSSDPARPG LSQQQWSSQK KAQVRSFPRA
KKLEKLGVFS SCKANDACKC NGWKNPNPPT AARMELQQQA ASLTETCRSC GHSLAEHVSH
LENVSEEEIN RLLGMVVDVE NLFMSVHKEE DTDTKQVYFY LFKLLRKCIL QMGKPVVEGS
LGSPPFEKPN IEQGVLNFVQ YKFSHLAPKE RQTMYELSKM FLLCLNYWKL ETPSQFRQRA
QKEDAAAYKV DYTRWLCYCH VPQSNDSLPR YETCQVFGRS LLKSIFTVTR RQLLEKFRVE
KDKLPPEKRT LILTHFPKFL SMLEEEIYGE NSPIWEADFT MPASEGTQLG HQTVLSPVSI
SGSPHSKGSS ASALGVTGLD VASSEPTIGE KRKLPEALTL EDAKRIRVMG DIPMELVNEV
MKTITDPAAM LGPETSLLSA NAARDETARL EERRGIIEFH VIGNSLSQKS NKKILMWLVG
LQNVFSHQLP RMPKEYITRL VFDPKHKTLA LIKDGRVIGG ICFRMFPTQG FTEIVFCAVT
SNEQVKGYGT HLMNHLKEYH IKHGILYFLT YADEYAIGYF KKQGFSKDIK VPKSRYLGYI
KDYEGATLME CELNPRIPYT ELSHIIKRQK EIIKKLIERK QNQIRKVYPG LTCFKEGVRQ
IPVESIPGIR ETGWKPSAKE KSKELKDPDL LYNMLKNLLA QIKTHPDAWP FMEPVKKSEA
PDYYEVIRFP IDLKTMTERL KNRYYVTKKL FIADLQRVIT NCREYNPPDS EYCKSANTLE
KFFYFKLKEA GLIDK
