KAT2A_HUMAN
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 03-AUG-2022, entry version 224.
DE RecName: Full=Histone acetyltransferase KAT2A;
DE EC=2.3.1.48 {ECO:0000269|PubMed:27377381, ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:31527837};
DE AltName: Full=General control of amino acid synthesis protein 5-like 2 {ECO:0000250|UniProtKB:Q9JHD2};
DE AltName: Full=Histone acetyltransferase GCN5 {ECO:0000303|PubMed:8552087, ECO:0000303|PubMed:9611240};
DE Short=hGCN5 {ECO:0000303|PubMed:8552087, ECO:0000303|PubMed:9611240};
DE AltName: Full=Histone glutaryltransferase KAT2A {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:31542297};
DE AltName: Full=Histone succinyltransferase KAT2A {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:29211711};
DE AltName: Full=Lysine acetyltransferase 2A {ECO:0000305};
DE AltName: Full=STAF97 {ECO:0000303|PubMed:11564863};
GN Name=KAT2A {ECO:0000303|PubMed:27796307, ECO:0000312|HGNC:HGNC:4201};
GN Synonyms=GCN5 {ECO:0000303|PubMed:8552087},
GN GCN5L2 {ECO:0000250|UniProtKB:Q9JHD2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), AND CHARACTERIZATION.
RC TISSUE=Testis;
RX PubMed=8552087; DOI=10.1128/mcb.16.2.593;
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 yeast
RT 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., Berger S.L.,
RA Nakatani Y., Allis C.D.;
RT "Cloning of Drosophila GCN5: conserved features among metazoan GCN5 family
RT 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 362-837 (ISOFORM 1), AND TISSUE
RP SPECIFICITY.
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 oncoprotein
RT E1A.";
RL Nature 382:319-324(1996).
RN [6]
RP SUBCELLULAR LOCATION, IDENTIFICATION IN THE STAGA COMPLEX WITH SUPT3H;
RP KIAA0764; TAF5L; TAF6L; TRRAP; TADA3L; TAF10; TAF12 AND TAF9, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 coactivator
RT that interacts with pre-mRNA splicing and DNA damage-binding factors in
RT vivo.";
RL Mol. Cell. Biol. 21:6782-6795(2001).
RN [7]
RP IDENTIFICATION IN THE TFTC-HAT COMPLEX WITH TAF5L; TAF6L; TADA3L; SUPT3H;
RP 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 hGCN5
RT to c-Myc.";
RL Mol. Cell. Biol. 20:556-562(2000).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), AND 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., Khochbin S.;
RT "The histone acetyltransferase, hGCN5, interacts with and acetylates the
RT 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) are
RT novel metazoan homologues of yeast TAFII47 containing a histone fold and a
RT 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 histone
RT 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 cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16753578; DOI=10.1016/j.cmet.2006.04.013;
RA Lerin C., Rodgers J.T., Kalume D.E., Kim S.H., Pandey A., Puigserver P.;
RT "GCN5 acetyltransferase complex controls glucose metabolism through
RT transcriptional repression of PGC-1alpha.";
RL Cell Metab. 3:429-438(2006).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH CEBPB.
RX PubMed=17301242; DOI=10.1073/pnas.0607378104;
RA Wiper-Bergeron N., Salem H.A., Tomlinson J.J., Wu D., Hache R.J.;
RT "Glucocorticoid-stimulated preadipocyte differentiation is mediated through
RT acetylation of C/EBPbeta by GCN5.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2703-2708(2007).
RN [15]
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., Georgieva S.G.,
RA 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 silencing.";
RL Mol. Cell 29:92-101(2008).
RN [16]
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 [17]
RP FUNCTION, CATALYTIC ACTIVITY, ACETYLATION AT LYS-549, PHOSPHORYLATION AT
RP SER-307 AND THR-735, AND MUTAGENESIS OF SER-307; LYS-549; MET-567; TYR-601;
RP 621-TYR-PHE-622 AND THR-735.
RX PubMed=23142079; DOI=10.1016/j.molcel.2012.09.030;
RA Dominy J.E. Jr., Lee Y., Jedrychowski M.P., Chim H., Jurczak M.J.,
RA Camporez J.P., Ruan H.B., Feldman J., Pierce K., Mostoslavsky R.,
RA Denu J.M., Clish C.B., Yang X., Shulman G.I., Gygi S.P., Puigserver P.;
RT "The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses
RT hepatic gluconeogenesis.";
RL Mol. Cell 48:900-913(2012).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, SUBCELLULAR LOCATION,
RP INTERACTION WITH PLK4, AND MUTAGENESIS OF GLU-575 AND ASP-615.
RX PubMed=27796307; DOI=10.1038/ncomms13227;
RA Fournier M., Orpinell M., Grauffel C., Scheer E., Garnier J.M., Ye T.,
RA Chavant V., Joint M., Esashi F., Dejaegere A., Goenczy P., Tora L.;
RT "KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in
RT preventing centrosome amplification.";
RL Nat. Commun. 7:13227-13227(2016).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TBX5.
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 [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-728; LYS-759 AND LYS-791, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [22]
RP SUBUNIT.
RX PubMed=30109122; DOI=10.1038/s41421-018-0048-8;
RA Wang Y., Guo Y.R., Xing D., Tao Y.J., Lu Z.;
RT "Supramolecular assembly of KAT2A with succinyl-CoA for histone
RT succinylation.";
RL Cell Discov. 4:47-47(2018).
RN [23]
RP FUNCTION, AND INTERACTION WITH XPC.
RX PubMed=29973595; DOI=10.1038/s41467-018-05010-0;
RA Bidon B., Iltis I., Semer M., Nagy Z., Larnicol A., Cribier A.,
RA Benkirane M., Coin F., Egly J.M., Le May N.;
RT "XPC is an RNA polymerase II cofactor recruiting ATAC to promoters by
RT interacting with E2F1.";
RL Nat. Commun. 9:2610-2610(2018).
RN [24]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31542297; DOI=10.1016/j.molcel.2019.08.018;
RA Bao X., Liu Z., Zhang W., Gladysz K., Fung Y.M.E., Tian G., Xiong Y.,
RA Wong J.W.H., Yuen K.W.Y., Li X.D.;
RT "Glutarylation of histone H4 lysine 91 regulates chromatin dynamics.";
RL Mol. Cell 0:0-0(2019).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, INTERACTION WITH XPC, AND
RP MUTAGENESIS OF GLU-575 AND ASP-615.
RX PubMed=31527837; DOI=10.1038/s41589-019-0354-y;
RA Semer M., Bidon B., Larnicol A., Caliskan G., Catez P., Egly J.M., Coin F.,
RA Le May N.;
RT "DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during
RT transcription.";
RL Nat. Chem. Biol. 15:992-1000(2019).
RN [26]
RP INTERACTION WITH ERCC3.
RX PubMed=30894545; DOI=10.1038/s41467-019-09270-2;
RA Sandoz J., Nagy Z., Catez P., Caliskan G., Geny S., Renaud J.B.,
RA Concordet J.P., Poterszman A., Tora L., Egly J.M., Le May N., Coin F.;
RT "Functional interplay between TFIIH and KAT2A regulates higher-order
RT chromatin structure and class II gene expression.";
RL Nat. Commun. 10:1288-1288(2019).
RN [27]
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 [28] {ECO:0007744|PDB:1Z4R}
RP X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 497-662 IN COMPLEX WITH
RP ACETYL-COA, AND ACTIVE SITE.
RX PubMed=17410582; DOI=10.1002/prot.21407;
RA Schuetz A., Bernstein G., Dong A., Antoshenko T., Wu H., Loppnau P.,
RA Bochkarev A., Plotnikov A.N.;
RT "Crystal structure of a binary complex between human GCN5 histone
RT acetyltransferase domain and acetyl coenzyme A.";
RL Proteins 68:403-407(2007).
RN [29]
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).
RN [30] {ECO:0007744|PDB:5H84, ECO:0007744|PDB:5H86}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 497-662 IN COMPLEX WITH
RP BUTYRYL-COA AND PROPIONYL-COA, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=27377381; DOI=10.1107/s2059798316007907;
RA Ringel A.E., Wolberger C.;
RT "Structural basis for acyl-group discrimination by human Gcn5L2.";
RL Acta Crystallogr. D 72:841-848(2016).
RN [31] {ECO:0007744|PDB:5TRL, ECO:0007744|PDB:5TRM}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 497-662 IN COMPLEX WITH
RP SUCCINYL-COA, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP DOMAIN, AND MUTAGENESIS OF TYR-645.
RX PubMed=29211711; DOI=10.1038/nature25003;
RA Wang Y., Guo Y.R., Liu K., Yin Z., Liu R., Xia Y., Tan L., Yang P.,
RA Lee J.H., Li X.J., Hawke D., Zheng Y., Qian X., Lyu J., He J., Xing D.,
RA Tao Y.J., Lu Z.;
RT "KAT2A coupled with the alpha-KGDH complex acts as a histone H3
RT succinyltransferase.";
RL Nature 552:273-277(2017).
CC -!- FUNCTION: Protein lysine acyltransferase that can act as a
CC acetyltransferase, glutaryltransferase or succinyltransferase,
CC depending on the context (PubMed:29211711). 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 (PubMed:29211711). Succinylation of histones gives a
CC specific tag for epigenetic transcription activation (PubMed:29211711).
CC Association with the 2-oxoglutarate dehydrogenase complex, which
CC provides succinyl-CoA, is required for histone succinylation
CC (PubMed:29211711). 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 (PubMed:17301242,
CC PubMed:19103755, PubMed:29211711). Has significant histone
CC acetyltransferase activity with core histones, but not with nucleosome
CC core particles (PubMed:17301242, PubMed:19103755). Acetylation of
CC histones gives a specific tag for epigenetic transcription activation
CC (PubMed:17301242, PubMed:19103755, PubMed:29211711). Recruited by the
CC XPC complex at promoters, where it specifically mediates acetylation of
CC histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target
CC genes (PubMed:29973595, PubMed:31527837). Involved in long-term memory
CC consolidation and synaptic plasticity: acts by promoting expression of
CC a hippocampal gene expression network linked to neuroactive receptor
CC signaling (By similarity). Acts as a positive regulator of T-cell
CC activation: upon TCR stimulation, recruited to the IL2 promoter
CC following interaction with NFATC2 and catalyzes acetylation of histone
CC H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (By
CC similarity). Required for growth and differentiation of craniofacial
CC cartilage and bone by regulating acetylation of histone H3 at 'Lys-9'
CC (H3K9ac) (By similarity). Regulates embryonic stem cell (ESC)
CC pluripotency and differentiation (By similarity). Also acetylates non-
CC histone proteins, such as CEBPB, PPARGC1A, PLK4 and TBX5
CC (PubMed:17301242, PubMed:16753578, PubMed:27796307, PubMed:29174768).
CC Involved in heart and limb development by mediating acetylation of
CC TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5
CC (PubMed:29174768). Acts as a negative regulator of centrosome
CC amplification by mediating acetylation of PLK4 (PubMed:27796307). Acts
CC as a negative regulator of gluconeogenesis by mediating acetylation and
CC subsequent inactivation of PPARGC1A (PubMed:16753578, PubMed:23142079).
CC Also acts as a histone glutaryltransferase: catalyzes glutarylation of
CC histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes
CC by promoting dissociation of the H2A-H2B dimers from nucleosomes
CC (PubMed:31542297). {ECO:0000250|UniProtKB:Q9JHD2,
CC ECO:0000269|PubMed:16753578, ECO:0000269|PubMed:17301242,
CC ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:23142079,
CC ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768,
CC ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:29973595,
CC ECO:0000269|PubMed:31527837, ECO:0000269|PubMed:31542297}.
CC -!- FUNCTION: (Microbial infection) In case of HIV-1 infection, it is
CC recruited by the viral protein Tat. Regulates Tat's transactivating
CC activity and may help inducing chromatin remodeling of proviral genes.
CC {ECO:0000269|PubMed:11384967}.
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;
CC Evidence={ECO:0000269|PubMed:16753578, ECO:0000269|PubMed:17301242,
CC ECO:0000269|PubMed:23142079, ECO:0000269|PubMed:27796307,
CC ECO:0000269|PubMed:29174768};
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:0000269|PubMed:27377381, ECO:0000269|PubMed:29211711,
CC ECO:0000269|PubMed:31527837};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993;
CC Evidence={ECO:0000269|PubMed:27377381, ECO:0000269|PubMed:29211711,
CC ECO:0000269|PubMed:31527837};
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:0000269|PubMed:29211711};
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:0000269|PubMed:31542297};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18010;
CC Evidence={ECO:0000269|PubMed:31542297};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.83 uM for acetyl-CoA {ECO:0000269|PubMed:29211711};
CC KM=0.91 uM for acetyl-CoA {ECO:0000269|PubMed:27377381};
CC KM=0.36 uM for succinyl-CoA {ECO:0000269|PubMed:29211711};
CC -!- SUBUNIT: Homooligomer; may form a tetramer of homodimers
CC (PubMed:30109122). Interacts with EP300, CREBBP and ADA2. Component of
CC the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L,
CC SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, KAT2A/GCN5L2,
CC TAF10 and TRRAP (PubMed:10373431, PubMed:10611234, PubMed:11438666).
CC Component of the STAGA transcription coactivator-HAT complex, at least
CC composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10,
CC TAF12, TRRAP and TAF9 (PubMed:18206972). The STAGA core complex is
CC associated with a subcomplex required for histone deubiquitination
CC composed of ATXN7L3, ENY2 and USP22 (PubMed:18206972). Component of the
CC ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L,
CC TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (PubMed:19103755). In
CC the complex, it probably interacts directly with KAT14, MBIP and WDR5
CC (PubMed:19103755). Interacts with PML (By similarity). Interacts with
CC CEBPB (PubMed:17301242). Interacts with TACC1, TACC2 and TACC3
CC (PubMed:14767476). Interacts with RELA (By similarity). Interacts with
CC NFATC2 (By similarity). Interacts with TBX5 (PubMed:29174768).
CC Interacts with PLK4 (PubMed:27796307). Associates with the 2-
CC oxoglutarate dehydrogenase complex (PubMed:29211711). Interacts with
CC XPC; leading to KAT2A recruitment to promoters and subsequent
CC acetylation of histones (PubMed:29973595, PubMed:31527837). Interacts
CC with ERCC3/XPB; leading to KAT2A recruitment to promoters and
CC subsequent acetylation of histones (PubMed:30894545).
CC {ECO:0000250|UniProtKB:Q9JHD2, ECO:0000269|PubMed:10373431,
CC ECO:0000269|PubMed:10611234, ECO:0000269|PubMed:11438666,
CC ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:17301242,
CC ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:19103755,
CC ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768,
CC ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:29973595,
CC ECO:0000269|PubMed:30109122, ECO:0000269|PubMed:30894545,
CC ECO:0000269|PubMed:31527837}.
CC -!- SUBUNIT: (Microbial infection) Interacts with and acetylates HIV-1 Tat.
CC {ECO:0000269|PubMed:11384967}.
CC -!- INTERACTION:
CC Q92830; Q9NY61: AATF; NbExp=4; IntAct=EBI-477622, EBI-372428;
CC Q92830; Q01094: E2F1; NbExp=3; IntAct=EBI-477622, EBI-448924;
CC Q92830; O75717: WDHD1; NbExp=5; IntAct=EBI-477622, EBI-3951691;
CC Q92830; Q8IYH5: ZZZ3; NbExp=2; IntAct=EBI-477622, EBI-2795524;
CC Q92830; P0DTC9: N; Xeno; NbExp=2; IntAct=EBI-477622, EBI-25475856;
CC Q92830; P59595: N; Xeno; NbExp=2; IntAct=EBI-477622, EBI-7602718;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11564863,
CC ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29211711}. Chromosome
CC {ECO:0000269|PubMed:29211711}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:27796307}.
CC Note=Mainly localizes to the nucleus (PubMed:27796307). Also localizes
CC to centrosomes in late G1 and around the G1/S transition, coinciding
CC with the onset of centriole formation (PubMed:27796307).
CC {ECO:0000269|PubMed:27796307}.
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.
CC {ECO:0000269|PubMed:8684459}.
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-645 has an important role in the selective binding
CC of succinyl-CoA over acetyl-CoA. {ECO:0000269|PubMed:29211711}.
CC -!- PTM: Acetylated at Lys-549, inhibiting the protein acetyltransferase
CC activity (PubMed:23142079). Deacetylation at Lys-549 by SIRT6 promotes
CC phosphorylation at Ser-307 and Thr-735 and subsequent activation of the
CC protein acetyltransferase activity, leading to acetylation and
CC inactivation of PPARGC1A (PubMed:23142079).
CC {ECO:0000269|PubMed:23142079}.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. GCN5 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: According to a report, has weak protein acyltransferase
CC activity compared to protein acetyltransferase activity
CC (PubMed:27377381). These conclusions are however not supported by
CC subsequent studies (PubMed:29211711, PubMed:31542297).
CC {ECO:0000269|PubMed:27377381, ECO:0000269|PubMed:29211711,
CC ECO:0000269|PubMed:31542297}.
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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 CCDS; CCDS11417.1; -. [Q92830-1]
DR PIR; S71789; S71789.
DR RefSeq; NP_066564.2; NM_021078.2. [Q92830-1]
DR RefSeq; XP_016879937.1; XM_017024448.1.
DR PDB; 1F68; NMR; -; A=730-832.
DR PDB; 1Z4R; X-ray; 1.74 A; A=497-662.
DR PDB; 3D7C; X-ray; 2.06 A; A/B=729-837.
DR PDB; 5H84; X-ray; 2.00 A; A=497-662.
DR PDB; 5H86; X-ray; 2.08 A; A=497-662.
DR PDB; 5MLJ; X-ray; 1.80 A; A/B=729-837.
DR PDB; 5TRL; X-ray; 2.30 A; A/B/C/D/E/F/G/H=497-662.
DR PDB; 5TRM; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=497-662.
DR PDB; 6J3P; X-ray; 1.60 A; A/B=726-837.
DR PDBsum; 1F68; -.
DR PDBsum; 1Z4R; -.
DR PDBsum; 3D7C; -.
DR PDBsum; 5H84; -.
DR PDBsum; 5H86; -.
DR PDBsum; 5MLJ; -.
DR PDBsum; 5TRL; -.
DR PDBsum; 5TRM; -.
DR PDBsum; 6J3P; -.
DR AlphaFoldDB; Q92830; -.
DR SMR; Q92830; -.
DR BioGRID; 108918; 166.
DR ComplexPortal; CPX-900; SAGA complex, KAT2A variant.
DR ComplexPortal; CPX-903; TFTC histone acetylation complex.
DR ComplexPortal; CPX-997; GCN5-containing ATAC complex.
DR CORUM; Q92830; -.
DR DIP; DIP-28146N; -.
DR IntAct; Q92830; 64.
DR MINT; Q92830; -.
DR STRING; 9606.ENSP00000225916; -.
DR BindingDB; Q92830; -.
DR ChEMBL; CHEMBL5501; -.
DR DrugBank; DB01992; Coenzyme A.
DR iPTMnet; Q92830; -.
DR PhosphoSitePlus; Q92830; -.
DR BioMuta; KAT2A; -.
DR DMDM; 209572743; -.
DR EPD; Q92830; -.
DR jPOST; Q92830; -.
DR MassIVE; Q92830; -.
DR MaxQB; Q92830; -.
DR PaxDb; Q92830; -.
DR PeptideAtlas; Q92830; -.
DR PRIDE; Q92830; -.
DR ProteomicsDB; 75506; -. [Q92830-1]
DR ProteomicsDB; 75507; -. [Q92830-2]
DR Antibodypedia; 29117; 363 antibodies from 34 providers.
DR DNASU; 2648; -.
DR Ensembl; ENST00000225916.10; ENSP00000225916.5; ENSG00000108773.11. [Q92830-1]
DR GeneID; 2648; -.
DR KEGG; hsa:2648; -.
DR MANE-Select; ENST00000225916.10; ENSP00000225916.5; NM_021078.3; NP_066564.2.
DR UCSC; uc002hyx.3; human. [Q92830-1]
DR CTD; 2648; -.
DR DisGeNET; 2648; -.
DR GeneCards; KAT2A; -.
DR HGNC; HGNC:4201; KAT2A.
DR HPA; ENSG00000108773; Low tissue specificity.
DR MIM; 602301; gene.
DR neXtProt; NX_Q92830; -.
DR OpenTargets; ENSG00000108773; -.
DR PharmGKB; PA162392664; -.
DR VEuPathDB; HostDB:ENSG00000108773; -.
DR eggNOG; KOG1472; Eukaryota.
DR GeneTree; ENSGT00940000158799; -.
DR HOGENOM; CLU_015901_0_0_1; -.
DR InParanoid; Q92830; -.
DR OMA; NHLKDYS; -.
DR OrthoDB; 349249at2759; -.
DR PhylomeDB; Q92830; -.
DR TreeFam; TF105399; -.
DR BRENDA; 2.3.1.48; 2681.
DR PathwayCommons; Q92830; -.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-HSA-8941856; RUNX3 regulates NOTCH signaling.
DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR SignaLink; Q92830; -.
DR SIGNOR; Q92830; -.
DR BioGRID-ORCS; 2648; 96 hits in 1096 CRISPR screens.
DR ChiTaRS; KAT2A; human.
DR EvolutionaryTrace; Q92830; -.
DR GeneWiki; GCN5L2; -.
DR GenomeRNAi; 2648; -.
DR Pharos; Q92830; Tchem.
DR PRO; PR:Q92830; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q92830; protein.
DR Bgee; ENSG00000108773; Expressed in right uterine tube and 184 other tissues.
DR ExpressionAtlas; Q92830; baseline and differential.
DR Genevisible; Q92830; HS.
DR GO; GO:0140672; C:ATAC complex; IDA:BHF-UCL.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0000123; C:histone acetyltransferase complex; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IC:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000124; C:SAGA complex; IDA:UniProtKB.
DR GO; GO:0033276; C:transcription factor TFTC complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0004402; F:histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0043997; F:histone acetyltransferase activity (H4-K12 specific); IEA:Ensembl.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0106229; F:histone glutaryltransferase activity; IDA:UniProtKB.
DR GO; GO:0106078; F:histone succinyltransferase activity; IDA:UniProtKB.
DR GO; GO:0061733; F:peptide-lysine-N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0071929; P:alpha-tubulin acetylation; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0016573; P:histone acetylation; IDA:UniProtKB.
DR GO; GO:0016578; P:histone deubiquitination; IDA:UniProtKB.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:UniProtKB.
DR GO; GO:0044154; P:histone H3-K14 acetylation; IDA:ComplexPortal.
DR GO; GO:0106077; P:histone succinylation; IDA:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0018393; P:internal peptidyl-lysine acetylation; IDA:UniProtKB.
DR GO; GO:0048312; P:intracellular distribution of mitochondria; IEA:Ensembl.
DR GO; GO:0060173; P:limb development; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; ISS:UniProtKB.
DR GO; GO:0022037; P:metencephalon development; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR GO; GO:0035521; P:monoubiquitinated histone deubiquitination; IDA:ComplexPortal.
DR GO; GO:0035522; P:monoubiquitinated histone H2A deubiquitination; IDA:ComplexPortal.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0046600; P:negative regulation of centriole replication; IDA:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0106227; P:peptidyl-lysine glutarylation; IDA:UniProtKB.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0031346; P:positive regulation of cell projection organization; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1903010; P:regulation of bone development; ISS:UniProtKB.
DR GO; GO:0061035; P:regulation of cartilage development; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:ComplexPortal.
DR GO; GO:0051302; P:regulation of cell division; IDA:ComplexPortal.
DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal.
DR GO; GO:0045995; P:regulation of embryonic development; IEA:Ensembl.
DR GO; GO:0031063; P:regulation of histone deacetylation; IMP:ComplexPortal.
DR GO; GO:0031647; P:regulation of protein stability; IMP:MGI.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; IC:ComplexPortal.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; 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 GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:ComplexPortal.
DR GO; GO:0090043; P:regulation of tubulin deacetylation; IMP:ComplexPortal.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR GO; GO:0021537; P:telencephalon development; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Alternative splicing;
KW Bromodomain; Chromosome; Cytoplasm; Cytoskeleton; Host-virus interaction;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..837
FT /note="Histone acetyltransferase KAT2A"
FT /id="PRO_0000211202"
FT DOMAIN 503..656
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT DOMAIN 745..815
FT /note="Bromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT REGION 1..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 639..648
FT /note="Loop 3"
FT /evidence="ECO:0000269|PubMed:29211711"
FT COMPBIAS 9..51
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..423
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 575
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:27796307,
FT ECO:0000269|PubMed:31527837"
FT BINDING 579..581
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:17410582,
FT ECO:0007744|PDB:1Z4R"
FT BINDING 579..581
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:29211711,
FT ECO:0007744|PDB:5TRL"
FT BINDING 586..592
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:17410582,
FT ECO:0007744|PDB:1Z4R"
FT BINDING 586..592
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:29211711,
FT ECO:0007744|PDB:5TRL"
FT BINDING 617
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:17410582,
FT ECO:0007744|PDB:1Z4R"
FT BINDING 617
FT /ligand="succinyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57292"
FT /evidence="ECO:0000269|PubMed:29211711,
FT ECO:0007744|PDB:5TRL"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23142079"
FT MOD_RES 549
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23142079"
FT MOD_RES 735
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:23142079"
FT CROSSLNK 728
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 759
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 791
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..410
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_000556"
FT MUTAGEN 307
FT /note="S->A: Slightly reduced ability to acetylate and
FT inhibit PPARGC1A. Strongly reduced ability to acetylate and
FT inhibit PPARGC1A; when associated with A-307 and Q-549."
FT /evidence="ECO:0000269|PubMed:23142079"
FT MUTAGEN 549
FT /note="K->Q: Mimics acetylation; reduced ability to
FT acetylate and inhibit PPARGC1A. Strongly reduced ability to
FT acetylate and inhibit PPARGC1A; when associated with A-307
FT and A-735."
FT /evidence="ECO:0000269|PubMed:23142079"
FT MUTAGEN 567
FT /note="M->A: Reduced ability to acetylate and inhibit
FT PPARGC1A."
FT /evidence="ECO:0000269|PubMed:23142079"
FT MUTAGEN 575
FT /note="E->A: Catalytically dead mutant; abolished
FT acyltransferase activity; when associated with A-615."
FT /evidence="ECO:0000269|PubMed:27796307,
FT ECO:0000269|PubMed:31527837"
FT MUTAGEN 601
FT /note="Y->F: Reduced ability to acetylate and inhibit
FT PPARGC1A."
FT /evidence="ECO:0000269|PubMed:23142079"
FT MUTAGEN 615
FT /note="D->A: Catalytically dead mutant; abolished
FT acyltransferase activity; when associated with A-575."
FT /evidence="ECO:0000269|PubMed:27796307,
FT ECO:0000269|PubMed:31527837"
FT MUTAGEN 621..622
FT /note="YF->AA: Abolised protein acetyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:23142079"
FT MUTAGEN 645
FT /note="Y->A: Reduced histone succinylation without
FT affecting histone acetylation. Reduced gene expression."
FT /evidence="ECO:0000269|PubMed:29211711"
FT MUTAGEN 735
FT /note="T->A: Slightly reduced ability to acetylate and
FT inhibit PPARGC1A. Strongly reduced ability to acetylate and
FT inhibit PPARGC1A; when associated with Q-549 and A-735."
FT /evidence="ECO:0000269|PubMed:23142079"
FT CONFLICT 116
FT /note="E -> G (in Ref. 1; AAC39769)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="M -> I (in Ref. 1; AAC39769)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="K -> E (in Ref. 1; AAC39769)"
FT /evidence="ECO:0000305"
FT STRAND 498..504
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 514..530
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 536..543
FT /evidence="ECO:0007829|PDB:1Z4R"
FT STRAND 549..555
FT /evidence="ECO:0007829|PDB:1Z4R"
FT STRAND 558..568
FT /evidence="ECO:0007829|PDB:1Z4R"
FT TURN 569..572
FT /evidence="ECO:0007829|PDB:1Z4R"
FT STRAND 573..581
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 583..585
FT /evidence="ECO:0007829|PDB:1Z4R"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 590..604
FT /evidence="ECO:0007829|PDB:1Z4R"
FT STRAND 609..614
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 616..618
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 619..624
FT /evidence="ECO:0007829|PDB:1Z4R"
FT STRAND 627..629
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 635..638
FT /evidence="ECO:0007829|PDB:1Z4R"
FT TURN 639..641
FT /evidence="ECO:0007829|PDB:1Z4R"
FT STRAND 649..654
FT /evidence="ECO:0007829|PDB:1Z4R"
FT HELIX 730..746
FT /evidence="ECO:0007829|PDB:6J3P"
FT HELIX 748..753
FT /evidence="ECO:0007829|PDB:6J3P"
FT TURN 759..761
FT /evidence="ECO:0007829|PDB:6J3P"
FT HELIX 765..768
FT /evidence="ECO:0007829|PDB:6J3P"
FT HELIX 775..783
FT /evidence="ECO:0007829|PDB:6J3P"
FT HELIX 790..807
FT /evidence="ECO:0007829|PDB:6J3P"
FT STRAND 810..812
FT /evidence="ECO:0007829|PDB:6J3P"
FT HELIX 813..831
FT /evidence="ECO:0007829|PDB:6J3P"
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
