KAT5_MOUSE
ID KAT5_MOUSE Reviewed; 513 AA.
AC Q8CHK4; A0A494B9U8; A1L394; Q3YFI9; Q8CGZ3; Q8CGZ4; Q8VIH0;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Histone acetyltransferase KAT5 {ECO:0000305};
DE EC=2.3.1.48 {ECO:0000305|PubMed:32542325};
DE AltName: Full=60 kDa Tat-interactive protein {ECO:0000303|PubMed:12036595};
DE Short=Tip60 {ECO:0000303|PubMed:12036595};
DE AltName: Full=Histone acetyltransferase HTATIP;
DE AltName: Full=Lysine acetyltransferase 5;
DE AltName: Full=Protein 2-hydroxyisobutyryltransferase KAT5 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q92993};
DE AltName: Full=Protein acetyltransferase KAT5 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:29765047, ECO:0000269|PubMed:31294688};
DE AltName: Full=Protein crotonyltransferase KAT5 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q92993};
GN Name=Kat5 {ECO:0000303|PubMed:30297694, ECO:0000312|MGI:MGI:1932051};
GN Synonyms=Htatip, Tip60 {ECO:0000303|PubMed:12036595};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=129/SvJ;
RX PubMed=12036595; DOI=10.1016/s0378-1119(02)00546-2;
RA McAllister D., Merlo X., Lough J.W.;
RT "Characterization and expression of the mouse tat interactive protein 60 kD
RT (TIP60) gene.";
RL Gene 289:169-176(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=12801643; DOI=10.1016/s0378-1119(03)00547-x;
RA Legube G., Trouche D.;
RT "Identification of a larger form of the histone acetyl transferase Tip60.";
RL Gene 310:161-168(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RA Szendro P.I., Cadenas C., Eichele G.;
RT "Cloning of mouse Tip60.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND INTERACTION WITH SRF.
RX PubMed=16597624; DOI=10.1074/jbc.m513593200;
RA Kim M.S., Merlo X., Wilson C., Lough J.;
RT "Co-activation of atrial natriuretic factor promoter by Tip60 and serum
RT response factor.";
RL J. Biol. Chem. 281:15082-15089(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC STRAIN=W/Wv;
RA Daigo Y., Takayama I., Fujino M.A.;
RT "Isolation and characterization of novel human and mouse genes, which are
RT expressed in the digestive tract.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5).
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 [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17728759; DOI=10.1038/nature06055;
RA Gorrini C., Squatrito M., Luise C., Syed N., Perna D., Wark L.,
RA Martinato F., Sardella D., Verrecchia A., Bennett S., Confalonieri S.,
RA Cesaroni M., Marchesi F., Gasco M., Scanziani E., Capra M., Mai S.,
RA Nuciforo P., Crook T., Lough J., Amati B.;
RT "Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-
RT induced DNA damage response.";
RL Nature 448:1063-1067(2007).
RN [9]
RP INTERACTION WITH FOXP3.
RX PubMed=19696312; DOI=10.1126/science.1176077;
RA Pan F., Yu H., Dang E.V., Barbi J., Pan X., Grosso J.F., Jinasena D.,
RA Sharma S.M., McCadden E.M., Getnet D., Drake C.G., Liu J.O.,
RA Ostrowski M.C., Pardoll D.M.;
RT "Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells.";
RL Science 325:1142-1146(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PHOSPHORYLATION AT
RP SER-86, AND MUTAGENESIS OF SER-86.
RX PubMed=22539723; DOI=10.1126/science.1217032;
RA Lin S.Y., Li T.Y., Liu Q., Zhang C., Li X., Chen Y., Zhang S.M., Lian G.,
RA Liu Q., Ruan K., Wang Z., Zhang C.S., Chien K.Y., Wu J., Li Q., Han J.,
RA Lin S.C.;
RT "GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to
RT autophagy.";
RL Science 336:477-481(2012).
RN [12]
RP FUNCTION.
RX PubMed=24835996; DOI=10.1016/j.celrep.2014.04.021;
RA Xiao Y., Nagai Y., Deng G., Ohtani T., Zhu Z., Zhou Z., Zhang H., Ji M.Q.,
RA Lough J.W., Samanta A., Hancock W.W., Greene M.I.;
RT "Dynamic interactions between TIP60 and p300 regulate FOXP3 function
RT through a structural switch defined by a single lysine on TIP60.";
RL Cell Rep. 7:1471-1480(2014).
RN [13]
RP FUNCTION.
RX PubMed=26291311; DOI=10.1038/cddis.2015.190;
RA Jang S.M., Kim J.W., Kim C.H., An J.H., Johnson A., Song P.I., Rhee S.,
RA Choi K.H.;
RT "KAT5-mediated SOX4 acetylation orchestrates chromatin remodeling during
RT myoblast differentiation.";
RL Cell Death Dis. 6:e1857-e1857(2015).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=28694333; DOI=10.1128/mcb.00082-17;
RA Dong Y., Isono K.I., Ohbo K., Endo T.A., Ohara O., Maekawa M., Toyama Y.,
RA Ito C., Toshimori K., Helin K., Ogonuki N., Inoue K., Ogura A.,
RA Yamagata K., Kitabayashi I., Koseki H.;
RT "EPC1/TIP60-mediated histone acetylation facilitates spermiogenesis in
RT mice.";
RL Mol. Cell. Biol. 37:0-0(2017).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-86, AND MUTAGENESIS OF
RP SER-86.
RX PubMed=29765047; DOI=10.1038/s41467-018-04363-w;
RA Li T.Y., Song L., Sun Y., Li J., Yi C., Lam S.M., Xu D., Zhou L., Li X.,
RA Yang Y., Zhang C.S., Xie C., Huang X., Shui G., Lin S.Y., Reue K.,
RA Lin S.C.;
RT "Tip60-mediated lipin 1 acetylation and ER translocation determine
RT triacylglycerol synthesis rate.";
RL Nat. Commun. 9:1916-1916(2018).
RN [16]
RP DISRUPTION PHENOTYPE (ISOFORM 5).
RX PubMed=30297694; DOI=10.1038/s41598-018-33213-4;
RA Acharya D., Nera B., Milstone Z.J., Bourke L., Yoon Y., Rivera-Perez J.A.,
RA Trivedi C.M., Fazzio T.G.;
RT "TIP55, a splice isoform of the KAT5 acetyltransferase, is essential for
RT developmental gene regulation and organogenesis.";
RL Sci. Rep. 8:14908-14908(2018).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31294688; DOI=10.7554/elife.43235;
RA Petkau N., Budak H., Zhou X., Oster H., Eichele G.;
RT "Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to
RT circadian promoters.";
RL Elife 8:0-0(2019).
RN [18]
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-86 AND SER-90, AND
RP MUTAGENESIS OF SER-86 AND SER-90.
RX PubMed=30297459; DOI=10.1128/mcb.00209-18;
RA Li M.L., Jiang Q., Bhanu N.V., Wu J., Li W., Garcia B.A., Greenberg R.A.;
RT "Phosphorylation of TIP60 Suppresses 53BP1 Localization at DNA Damage
RT Sites.";
RL Mol. Cell. Biol. 39:0-0(2019).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN NUA4 COMPLEX, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF 377-GLN--GLY-380.
RX PubMed=32542325; DOI=10.1182/blood.2019001279;
RA Numata A., Kwok H.S., Zhou Q.L., Li J., Tirado-Magallanes R.,
RA Angarica V.E., Hannah R., Park J., Wang C.Q., Krishnan V., Rajagopalan D.,
RA Zhang Y., Zhou S., Welner R.S., Osato M., Jha S., Bohlander S.K.,
RA Goettgens B., Yang H., Benoukraf T., Lough J.W., Bararia D., Tenen D.G.;
RT "Lysine acetyltransferase Tip60 is required for hematopoietic stem cell
RT maintenance.";
RL Blood 136:1735-1747(2020).
RN [20]
RP PHOSPHORYLATION.
RX PubMed=33076429; DOI=10.3390/cancers12102986;
RA Garcia-Gonzalez R., Morejon-Garcia P., Campillo-Marcos I., Salzano M.,
RA Lazo P.A.;
RT "VRK1 phosphorylates Tip60/KAT5 and is required for H4K16 acetylation in
RT response to DNA Damage.";
RL Cancers 12:0-0(2020).
RN [21]
RP MUTAGENESIS OF SER-86.
RX PubMed=32817552; DOI=10.1073/pnas.1922330117;
RA Song Z.M., Lin H., Yi X.M., Guo W., Hu M.M., Shu H.B.;
RT "KAT5 acetylates cGAS to promote innate immune response to DNA virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:21568-21575(2020).
RN [22]
RP PHOSPHORYLATION AT SER-90, AND MUTAGENESIS OF SER-90.
RX PubMed=34608293; DOI=10.1038/s41589-021-00875-7;
RA Song X., Yang F., Liu X., Xia P., Yin W., Wang Z., Wang Y., Yuan X.,
RA Dou Z., Jiang K., Ma M., Hu B., Zhang R., Xu C., Zhang Z., Ruan K.,
RA Tian R., Li L., Liu T., Hill D.L., Zang J., Liu X., Li J., Cheng J.,
RA Yao X.;
RT "Dynamic crotonylation of EB1 by TIP60 ensures accurate spindle positioning
RT in mitosis.";
RL Nat. Chem. Biol. 17:1314-1323(2021).
CC -!- FUNCTION: Catalytic subunit of the NuA4 histone acetyltransferase
CC complex, a multiprotein complex involved in transcriptional activation
CC of select genes principally by acetylation of nucleosomal histones H2A
CC and H4 (PubMed:28694333, PubMed:30297459, PubMed:32542325). Histone
CC acetylation alters nucleosome-DNA interactions and promotes interaction
CC of the modified histones with other proteins which positively regulate
CC transcription (By similarity). The NuA4 histone acetyltransferase
CC complex is required for the activation of transcriptional programs
CC associated with proto-oncogene mediated growth induction, tumor
CC suppressor mediated growth arrest and replicative senescence,
CC apoptosis, and DNA repair (PubMed:17728759). The NuA4 complex plays a
CC direct role in repair of DNA double-strand breaks (DSBs) by promoting
CC homologous recombination (HR): the complex inhibits TP53BP1 binding to
CC chromatin via MBTD1, which recognizes and binds histone H4
CC trimethylated at 'Lys-20' (H4K20me), and KAT5 that catalyzes
CC acetylation of 'Lys-15' of histone H2A (H2AK15ac), thereby blocking the
CC ubiquitination mark required for TP53BP1 localization at DNA breaks
CC (PubMed:30297459). Also involved in DSB repair by mediating acetylation
CC of 'Lys-5' of histone H2AX (H2AXK5ac), promoting NBN/NBS1 assembly at
CC the sites of DNA damage (By similarity). The NuA4 complex plays a key
CC role in hematopoietic stem cell maintenance and is required to maintain
CC acetylated H2A.Z/H2AZ1 at MYC target genes (PubMed:32542325). The NuA4
CC complex is also required for spermatid development by promoting
CC acetylation of histones: histone hyperacetylation is required for
CC histone replacement during the transition from round to elongating
CC spermatids (PubMed:28694333). Component of a SWR1-like complex that
CC specifically mediates the removal of histone H2A.Z/H2AZ1 from the
CC nucleosome (By similarity). Also acetylates non-histone proteins, such
CC as ARNTL/BMAL1, ATM, AURKB, CHKA, CGAS, ERCC4/XPF, LPIN1, NDC80/HEC1,
CC NR1D2, RAN, SOX4, FOXP3, ULK1 and RUBCNL/Pacer (PubMed:22539723,
CC PubMed:24835996, PubMed:31294688). Directly acetylates and activates
CC ATM (By similarity). Promotes nucleotide excision repair (NER) by
CC mediating acetylation of ERCC4/XPF, thereby promoting formation of the
CC ERCC4-ERCC1 complex (By similarity). Relieves NR1D2-mediated inhibition
CC of APOC3 expression by acetylating NR1D2 (By similarity). Acts as a
CC regulator of regulatory T-cells (Treg) by catalyzing FOXP3 acetylation,
CC thereby promoting FOXP3 transcriptional repressor activity
CC (PubMed:24835996). Involved in skeletal myoblast differentiation by
CC mediating acetylation of SOX4 (PubMed:26291311). Catalyzes acetylation
CC of APBB1/FE65, increasing its transcription activator activity (By
CC similarity). Promotes transcription elongation during the activation
CC phase of the circadian cycle by catalyzing acetylation of ARNTL/BMAL1,
CC promoting elongation of circadian transcripts (PubMed:31294688).
CC Together with GSK3 (GSK3A or GSK3B), acts as a regulator of autophagy:
CC phosphorylated at Ser-86 by GSK3 under starvation conditions, leading
CC to activate acetyltransferase activity and promote acetylation of key
CC autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:22539723).
CC Acts as a regulator of the cGAS-STING innate antiviral response by
CC catalyzing acetylation the N-terminus of CGAS, thereby promoting CGAS
CC DNA-binding and activation (By similarity). Also regulates lipid
CC metabolism by mediating acetylation of CHKA or LPIN1 (PubMed:29765047).
CC Promotes lipolysis of lipid droplets following glucose deprivation by
CC mediating acetylation of isoform 1 of CHKA, thereby promoting
CC monomerization of CHKA and its conversion into a tyrosine-protein
CC kinase (By similarity). Acts as a regulator of fatty-acid-induced
CC triacylglycerol synthesis by catalyzing acetylation of LPIN1, thereby
CC promoting the synthesis of diacylglycerol (PubMed:29765047). In
CC addition to protein acetyltransferase, can use different acyl-CoA
CC substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA) and 2-
CC hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), and is able to
CC mediate protein crotonylation and 2-hydroxyisobutyrylation,
CC respectively (By similarity). Acts as a key regulator of chromosome
CC segregation and kinetochore-microtubule attachment during mitosis by
CC mediating acetylation or crotonylation of target proteins (By
CC similarity). Catalyzes acetylation of AURKB at kinetochores, increasing
CC AURKB activity and promoting accurate chromosome segregation in mitosis
CC (By similarity). Acetylates RAN during mitosis, promoting microtubule
CC assembly at mitotic chromosomes (By similarity). Acetylates NDC80/HEC1
CC during mitosis, promoting robust kinetochore-microtubule attachment (By
CC similarity). Catalyzes crotonylation of MAPRE1/EB1, thereby ensuring
CC accurate spindle positioning in mitosis (By similarity).
CC {ECO:0000250|UniProtKB:Q92993, ECO:0000269|PubMed:17728759,
CC ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:24835996,
CC ECO:0000269|PubMed:26291311, ECO:0000269|PubMed:28694333,
CC ECO:0000269|PubMed:29765047, ECO:0000269|PubMed:30297459,
CC ECO:0000269|PubMed:31294688, ECO:0000269|PubMed:32542325}.
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:0000305|PubMed:32542325};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993;
CC Evidence={ECO:0000305|PubMed:32542325};
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:0000269|PubMed:22539723, ECO:0000269|PubMed:29765047,
CC ECO:0000269|PubMed:31294688};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45949;
CC Evidence={ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:29765047,
CC ECO:0000269|PubMed:31294688};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-butenoyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-
CC (2E)-butenoyl-L-lysyl-[protein]; Xref=Rhea:RHEA:53908, Rhea:RHEA-
CC COMP:9752, Rhea:RHEA-COMP:13707, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57332,
CC ChEBI:CHEBI:137954; Evidence={ECO:0000250|UniProtKB:Q92993};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53909;
CC Evidence={ECO:0000250|UniProtKB:Q92993};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyisobutanoyl-CoA + L-lysyl-[protein] = CoA + H(+) +
CC N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein]; Xref=Rhea:RHEA:24180,
CC Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:15921, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:131780,
CC ChEBI:CHEBI:144968; Evidence={ECO:0000250|UniProtKB:Q92993};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24181;
CC Evidence={ECO:0000250|UniProtKB:Q92993};
CC -!- ACTIVITY REGULATION: Acyltransferase and acetyltransferase activities
CC are activated by phosphorylation and autoacetylation (PubMed:22539723).
CC Autoacetylation activates the histone acetyltransferase activity (By
CC similarity). {ECO:0000250|UniProtKB:Q9H7Z6,
CC ECO:0000269|PubMed:22539723}.
CC -!- SUBUNIT: Component of the NuA4 histone acetyltransferase complex which
CC contains the catalytic subunit KAT5/TIP60 and the subunits EP400,
CC TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2,
CC ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP,
CC YEATS4/GAS41, VPS72/YL1 and MEAF6 (PubMed:32542325). KAT5/TIP60, EPC1,
CC and ING3 together constitute a minimal HAT complex termed Piccolo NuA4
CC (By similarity). The NuA4 complex interacts with MYC (By similarity).
CC Interacts with ATM (By similarity). Interacts with JADE1 (By
CC similarity). Interacts with PLA2G4A/CPLA2, EDNRA and HDAC7 (By
CC similarity). Interacts with the cytoplasmic tail of APP and APBB1/FE65
CC (By similarity). Interacts with TRIM24 and TRIM68 (By similarity).
CC Forms a complex with SENP6 and UBE2I in response to UV irradiation (By
CC similarity). Identified in a complex with HINT1 (By similarity).
CC Interacts with ATF2 and CUL3 (By similarity). Interacts with NR1D2 (via
CC N-terminus) (By similarity). Component of a SWR1-like complex (By
CC similarity). Interacts with FOXP3 (PubMed:19696312). Interacts with
CC ZBTB49 (By similarity). Interacts with SRF (PubMed:16597624). Interacts
CC with ATF3; promoting autoacetylation and deubiquitination by USP7 (By
CC similarity). Interacts with EP300/p300; interaction promotes KAT5
CC autoacetylation (By similarity). Interacts with PRKDC; interaction is
CC impaired following KAT5 sumoylation (By similarity).
CC {ECO:0000250|UniProtKB:Q92993, ECO:0000269|PubMed:16597624,
CC ECO:0000269|PubMed:19696312, ECO:0000269|PubMed:32542325}.
CC -!- INTERACTION:
CC Q8CHK4; P54254: Atxn1; NbExp=2; IntAct=EBI-1169948, EBI-1169713;
CC Q8CHK4; O88495: Gpr50; NbExp=3; IntAct=EBI-1169948, EBI-21227860;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28694333}. Chromosome
CC {ECO:0000250|UniProtKB:Q92993}. Cytoplasm
CC {ECO:0000269|PubMed:28694333}. Chromosome, centromere, kinetochore
CC {ECO:0000250|UniProtKB:Q92993}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250|UniProtKB:Q92993}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:12036595}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q92993}. Note=Upon stimulation with EDN1, it is
CC exported from the nucleus to the perinuclear region and UV irradiation
CC induces translocation into punctuate subnuclear structures named
CC nuclear bodies (By similarity). Transiently localizes to kinetochores
CC in early mitosis (By similarity). Localizes to spindle poles when
CC chromosomes align during metaphase (By similarity). Localizes in the
CC cytoplasm and nucleus of round spermatids (PubMed:28694333).
CC {ECO:0000250|UniProtKB:Q92993, ECO:0000269|PubMed:28694333}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Tip60alpha {ECO:0000303|PubMed:16597624};
CC IsoId=Q8CHK4-1; Sequence=Displayed;
CC Name=2; Synonyms=Tip60beta {ECO:0000303|PubMed:16597624};
CC IsoId=Q8CHK4-2; Sequence=VSP_009107;
CC Name=3; Synonyms=Ltip60 {ECO:0000303|PubMed:12801643};
CC IsoId=Q8CHK4-3; Sequence=VSP_009106;
CC Name=4;
CC IsoId=Q8CHK4-4; Sequence=VSP_009105;
CC Name=5; Synonyms=Tip55 {ECO:0000303|PubMed:16597624};
CC IsoId=Q8CHK4-5; Sequence=VSP_061400, VSP_061401;
CC -!- TISSUE SPECIFICITY: Expressed in testis, heart, brain, kidney and
CC liver. Weakly expressed in lung. {ECO:0000269|PubMed:12036595}.
CC -!- PTM: Phosphorylated on Ser-86 and Ser-90; enhanced during G2/M phase
CC (PubMed:22539723, PubMed:30297459, PubMed:34608293). The phosphorylated
CC form has a higher activity (PubMed:30297459, PubMed:34608293).
CC Phosphorylation at Ser-90 by CDK1 or CDK9 is a prerequisite for
CC phosphorylation at Ser-86 by GSK3 (PubMed:34608293). Phosphorylation at
CC Ser-86 by GSK3 (GSK3A or GSK3B) activates acetyltransferase and
CC acyltransferase activity (PubMed:22539723, PubMed:30297459).
CC Phosphorylation at Ser-90 by CDK9 promotes KAT5 recruitment to
CC chromatin (By similarity). Phosphorylation by VRK1 following DNA damage
CC promotes KAT5 association with chromatin and histone acetyltransferase
CC activity (PubMed:33076429). {ECO:0000250|UniProtKB:Q9H7Z6,
CC ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:30297459,
CC ECO:0000269|PubMed:33076429, ECO:0000269|PubMed:34608293}.
CC -!- PTM: Autoacetylated (By similarity). Autoacetylation is required for
CC histone acetyltransferase activity (By similarity). Autoacetylation at
CC Lys-327 is facilitated by interaction with EP300/p300: it prevents
CC ubiquitination and subsequent degradation by the proteasome and
CC promotes acetylation of target proteins (By similarity). Deacetylated
CC by HDAC3 and SIRT1 (By similarity). Deacetylation by HDAC3 promotes its
CC ubiquitination and cytoplasmic localization (By similarity).
CC {ECO:0000250|UniProtKB:Q9H7Z6}.
CC -!- PTM: Sumoylated by UBE2I at Lys-430 and Lys-451, leading to increase of
CC its histone acetyltransferase activity in UV-induced DNA damage
CC response, as well as its translocation to nuclear bodies (By
CC similarity). Sumoylation with SUMO2 by PIAS4 at Lys-430 promotes repair
CC of DNA double-strand breaks (DSBs) via homologous recombination (HR)
CC (By similarity). Sumoylation by PIAS4 impairs interaction with PRKDC,
CC inhibiting non-homologous end joining (NHEJ)-mediated repair of DSBs,
CC thereby facilitating HR (By similarity). Desumoylated by SENP3 (By
CC similarity). {ECO:0000250|UniProtKB:Q92993}.
CC -!- PTM: Ubiquitinated by MDM2, leading to its proteasome-dependent
CC degradation (By similarity). Ubiquitination is prevented by
CC autoacetylation at Lys-327 (By similarity). Ubiquitinated following
CC deacetylation by HDAC3, leading to cytoplasmic localization (By
CC similarity). Deubiquitinated by USP7 following interaction with ATF3,
CC promoting its stabilization (By similarity).
CC {ECO:0000250|UniProtKB:Q92993}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality before implantation
CC (PubMed:17728759). Conditional deletion leads to rapid hematopoietic
CC stem cell loss in both fetal and adult stages (PubMed:32542325).
CC Conditional deletion at postnatal day 15 leads to impaired spermatid
CC development: testes are smaller and show defects in the transition from
CC the transition from round to elongating spermatids (PubMed:28694333).
CC Defects in spermatid development is probably caused by impaired
CC acetylation of histones that affects histone replacement
CC (PubMed:28694333). Conditional deletion in response to DNA damage leads
CC to impaired homologous recombination (HR)repair in response to DNA
CC double-strand breaks (DSBs), associated with increased non-homologous
CC end joining (NHEJ)-mediated repair mediated by TP53BP1
CC (PubMed:30297459). {ECO:0000269|PubMed:17728759,
CC ECO:0000269|PubMed:28694333, ECO:0000269|PubMed:30297459,
CC ECO:0000269|PubMed:32542325}.
CC -!- DISRUPTION PHENOTYPE: [Isoform 5]: Mice lacking isoform 5 die during
CC mid-gestation (around embryonic day 11.5) (PubMed:30297694). Prior to
CC developmental arrest, embryos display defects in heart and neural tube
CC (PubMed:30297694). Specification of cardiac and neural cell fates is
CC first normal; however, cell division and survival are impaired in heart
CC and neural tube, respectively (PubMed:30297694).
CC {ECO:0000269|PubMed:30297694}.
CC -!- SIMILARITY: Belongs to the MYST (SAS/MOZ) family. {ECO:0000305}.
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DR EMBL; AY061983; AAL34981.1; -; Genomic_DNA.
DR EMBL; AF528194; AAN77140.1; -; mRNA.
DR EMBL; AF528195; AAN77141.1; -; mRNA.
DR EMBL; AF528196; AAN77142.1; -; mRNA.
DR EMBL; DQ139980; AAZ67923.1; -; mRNA.
DR EMBL; AB055409; BAC53807.1; -; mRNA.
DR EMBL; BC129968; AAI29969.1; -; mRNA.
DR EMBL; BC110675; AAI10676.1; -; mRNA.
DR CCDS; CCDS29472.1; -. [Q8CHK4-1]
DR CCDS; CCDS89314.1; -. [Q8CHK4-2]
DR RefSeq; NP_001186176.1; NM_001199247.1. [Q8CHK4-2]
DR RefSeq; NP_001186177.1; NM_001199248.1.
DR RefSeq; NP_848752.1; NM_178637.2. [Q8CHK4-1]
DR AlphaFoldDB; Q8CHK4; -.
DR SMR; Q8CHK4; -.
DR BioGRID; 219884; 59.
DR ComplexPortal; CPX-747; Piccolo NuA4 histone acetyltransferase complex.
DR ComplexPortal; CPX-990; NuA4 histone acetyltransferase complex.
DR IntAct; Q8CHK4; 29.
DR MINT; Q8CHK4; -.
DR STRING; 10090.ENSMUSP00000109271; -.
DR iPTMnet; Q8CHK4; -.
DR PhosphoSitePlus; Q8CHK4; -.
DR EPD; Q8CHK4; -.
DR jPOST; Q8CHK4; -.
DR MaxQB; Q8CHK4; -.
DR PaxDb; Q8CHK4; -.
DR PeptideAtlas; Q8CHK4; -.
DR PRIDE; Q8CHK4; -.
DR ProteomicsDB; 301733; -. [Q8CHK4-1]
DR ProteomicsDB; 301734; -. [Q8CHK4-2]
DR ProteomicsDB; 301735; -. [Q8CHK4-3]
DR ProteomicsDB; 301736; -. [Q8CHK4-4]
DR Antibodypedia; 1823; 739 antibodies from 38 providers.
DR DNASU; 81601; -.
DR Ensembl; ENSMUST00000113641; ENSMUSP00000109271; ENSMUSG00000024926. [Q8CHK4-1]
DR Ensembl; ENSMUST00000236229; ENSMUSP00000158391; ENSMUSG00000024926. [Q8CHK4-2]
DR Ensembl; ENSMUST00000236883; ENSMUSP00000157766; ENSMUSG00000024926. [Q8CHK4-5]
DR GeneID; 81601; -.
DR KEGG; mmu:81601; -.
DR UCSC; uc008gdy.2; mouse. [Q8CHK4-1]
DR UCSC; uc008geb.2; mouse. [Q8CHK4-2]
DR CTD; 10524; -.
DR MGI; MGI:1932051; Kat5.
DR VEuPathDB; HostDB:ENSMUSG00000024926; -.
DR eggNOG; KOG2747; Eukaryota.
DR GeneTree; ENSGT00940000162343; -.
DR HOGENOM; CLU_011815_2_0_1; -.
DR InParanoid; Q8CHK4; -.
DR OMA; SMTQNQT; -.
DR OrthoDB; 629545at2759; -.
DR PhylomeDB; Q8CHK4; -.
DR TreeFam; TF317619; -.
DR Reactome; R-MMU-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-MMU-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression.
DR BioGRID-ORCS; 81601; 22 hits in 114 CRISPR screens.
DR ChiTaRS; Kat5; mouse.
DR PRO; PR:Q8CHK4; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8CHK4; protein.
DR Bgee; ENSMUSG00000024926; Expressed in retinal neural layer and 232 other tissues.
DR ExpressionAtlas; Q8CHK4; baseline and differential.
DR Genevisible; Q8CHK4; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0000776; C:kinetochore; ISS:UniProtKB.
DR GO; GO:0097431; C:mitotic spindle pole; ISO:MGI.
DR GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000786; C:nucleosome; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032777; C:Piccolo NuA4 histone acetyltransferase complex; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0000812; C:Swr1 complex; ISS:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043998; F:H2A histone acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0004402; F:histone acetyltransferase activity; IMP:UniProtKB.
DR GO; GO:0043999; F:histone acetyltransferase activity (H2A-K5 specific); ISO:MGI.
DR GO; GO:0046972; F:histone acetyltransferase activity (H4-K16 specific); ISO:MGI.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106226; F:peptide 2-hydroxyisobutyryltransferase activity; IEA:RHEA.
DR GO; GO:0140065; F:peptide butyryltransferase activity; ISS:UniProtKB.
DR GO; GO:0140064; F:peptide crotonyltransferase activity; ISS:UniProtKB.
DR GO; GO:0061733; F:peptide-lysine-N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0043274; F:phospholipase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:MGI.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; ISO:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:MGI.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISO:MGI.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISS:UniProtKB.
DR GO; GO:0016573; P:histone acetylation; IMP:UniProtKB.
DR GO; GO:0043968; P:histone H2A acetylation; ISO:MGI.
DR GO; GO:0043967; P:histone H4 acetylation; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1905691; P:lipid droplet disassembly; ISS:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0021915; P:neural tube development; IDA:MGI.
DR GO; GO:0022008; P:neurogenesis; IDA:MGI.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0018394; P:peptidyl-lysine acetylation; IDA:UniProtKB.
DR GO; GO:1902425; P:positive regulation of attachment of mitotic spindle microtubules to kinetochore; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:1900051; P:positive regulation of histone exchange; IMP:UniProtKB.
DR GO; GO:0062033; P:positive regulation of mitotic sister chromatid segregation; ISS:UniProtKB.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:1901985; P:positive regulation of protein acetylation; ISO:MGI.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0006473; P:protein acetylation; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IC:ComplexPortal.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
DR GO; GO:1902275; P:regulation of chromatin organization; IC:ComplexPortal.
DR GO; GO:2000779; P:regulation of double-strand break repair; IC:ComplexPortal.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0010212; P:response to ionizing radiation; ISO:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR016197; Chromo-like_dom_sf.
DR InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR InterPro; IPR002717; HAT_MYST-type.
DR InterPro; IPR037995; KAT5/Tip60.
DR InterPro; IPR025995; Tudor-knot.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR040706; Zf-MYST.
DR PANTHER; PTHR10615:SF183; PTHR10615:SF183; 1.
DR Pfam; PF01853; MOZ_SAS; 1.
DR Pfam; PF11717; Tudor-knot; 1.
DR Pfam; PF17772; zf-MYST; 1.
DR SMART; SM00298; CHROMO; 1.
DR SUPFAM; SSF54160; SSF54160; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51726; MYST_HAT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Acyltransferase; Alternative splicing; Centromere;
KW Chromatin regulator; Chromosome; Cytoplasm; Cytoskeleton; DNA damage;
KW DNA repair; Growth regulation; Immunity; Innate immunity; Isopeptide bond;
KW Kinetochore; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Zinc; Zinc-finger.
FT CHAIN 1..513
FT /note="Histone acetyltransferase KAT5"
FT /id="PRO_0000051581"
FT DOMAIN 8..65
FT /note="Tudor-knot"
FT /evidence="ECO:0000255"
FT DOMAIN 227..504
FT /note="MYST-type HAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01063"
FT ZN_FING 260..285
FT /note="C2HC MYST-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01063"
FT REGION 69..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 122..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..513
FT /note="Interaction with ATF2"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT ACT_SITE 403
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT BINDING 370..372
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT BINDING 377..383
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT BINDING 407
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT BINDING 416
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT MOD_RES 52
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22539723,
FT ECO:0000269|PubMed:29765047, ECO:0000269|PubMed:30297459"
FT MOD_RES 90
FT /note="Phosphoserine; by CDK1 and CDK9"
FT /evidence="ECO:0000269|PubMed:30297459,
FT ECO:0000269|PubMed:34608293"
FT MOD_RES 104
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT MOD_RES 120
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT MOD_RES 148
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT MOD_RES 150
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT MOD_RES 187
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT MOD_RES 189
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 327
FT /note="N6-acetyllysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT CROSSLNK 451
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q92993"
FT VAR_SEQ 1..211
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_009105"
FT VAR_SEQ 4
FT /note="V -> VVSPVPGAGRREPGEVGRARGPPVADPGVALSPQ (in isoform
FT 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_009106"
FT VAR_SEQ 96..147
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_009107"
FT VAR_SEQ 390..492
FT /note="YELSKVEGKTGTPEKPLSDLGLLSYRSYWSQTILEILMGLKSESGERPQITI
FT NEISEITSIKKEDVISTLQYLNLINYYKGQYILTLSEDIVDGHERAMLKRL -> EYVL
FT PDQELAGQACVGPILLRAAGVPRIAAKLMTLKRFPCPQTTKGSLITAIHPDTGWQGSDP
FT SWQPSLADKYPTRAALLAFGPQHCRQGSCWSTPRAMNSRK (in isoform 5)"
FT /id="VSP_061400"
FT VAR_SEQ 493..513
FT /note="Missing (in isoform 5)"
FT /id="VSP_061401"
FT MUTAGEN 86
FT /note="S->A: Abolished phosphorylation by GSK3 and
FT decreased acetyltransferase activity. Impaired ability to
FT activate the cGAS-STING antiviral response in knockin mice.
FT Lean phenotype caused by impaired ability to promote the
FT synthesis of diacylglycerol in knockin mice. Decreased
FT ability to promote homologous recombination (HR)repair in
FT response to DNA double-strand breaks (DSBs)."
FT /evidence="ECO:0000269|PubMed:22539723,
FT ECO:0000269|PubMed:29765047, ECO:0000269|PubMed:30297459,
FT ECO:0000269|PubMed:32817552"
FT MUTAGEN 86
FT /note="S->D: Mimics phosphorylation; constitutively active
FT mutant that shows constitutive protein acetyltransferase
FT activity. Increased ability to promote homologous
FT recombination (HR)repair in response to DNA double-strand
FT breaks (DSBs)."
FT /evidence="ECO:0000269|PubMed:30297459"
FT MUTAGEN 90
FT /note="S->A: Impaired phosphorylation and decreased
FT acetyltransferase activity, leading to decreased ability to
FT promote homologous recombination (HR)repair in response to
FT DNA double-strand breaks (DSBs)."
FT /evidence="ECO:0000269|PubMed:30297459"
FT MUTAGEN 90
FT /note="S->D: Mimics phosphorylation; constitutively active
FT mutant that shows constitutive protein acetyltransferase
FT and acyltransferase activities in knockin mice. Increased
FT ability to promote homologous recombination (HR)repair in
FT response to DNA double-strand breaks (DSBs)."
FT /evidence="ECO:0000269|PubMed:30297459,
FT ECO:0000269|PubMed:34608293"
FT MUTAGEN 377..380
FT /note="QRRG->ERRE: Abolished acetyltransferase activity."
FT /evidence="ECO:0000269|PubMed:32542325"
FT CONFLICT Q8CHK4-5:465
FT /note="R -> G (in Ref. 4; AAZ67923.1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 513 AA; 58598 MW; EACEE4D544C0DB60 CRC64;
MAEVGEIIEG CRLPVLRRNQ DNEDEWPLAE ILSVKDISGR KLFYVHYIDF NKRLDEWVTH
ERLDLKKIQF PKKEAKTPTK NGLPGSRPGS PEREVPASAQ ASGKTLPIPV QITLRFNLPK
EREAIPGGEP DQPLSSSSCL QPNHRSTKRK VEVVSPATPV PSETAPASVF PQNGSARRAV
AAQPGRKRKS NCLGTDEDSQ DSSDGIPSAP RMTGSLVSDR SHDDIVTRMK NIECIELGRH
RLKPWYFSPY PQELTTLPVL YLCEFCLKYG RSLKCLQRHL TKCDLRHPPG NEIYRKGTIS
FFEIDGRKNK SYSQNLCLLA KCFLDHKTLY YDTDPFLFYV MTEYDCKGFH IVGYFSKEKE
STEDYNVACI LTLPPYQRRG YGKLLIEFSY ELSKVEGKTG TPEKPLSDLG LLSYRSYWSQ
TILEILMGLK SESGERPQIT INEISEITSI KKEDVISTLQ YLNLINYYKG QYILTLSEDI
VDGHERAMLK RLLRIDSKCL HFTPKDWSKR GKW
