ID   TIP60_DROME             Reviewed;         541 AA.
AC   Q960X4; O97425;
DT   07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=Histone acetyltransferase Tip60 {ECO:0000305};
DE            EC=2.3.1.48 {ECO:0000269|PubMed:15528408};
GN   Name=Tip60 {ECO:0000303|PubMed:15528408,
GN   ECO:0000312|FlyBase:FBgn0026080}; ORFNames=CG6121;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Oregon-R;
RX   PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA   Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA   Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA   Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA   Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA   Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA   Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA   McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA   Glover D.M.;
RT   "From sequence to chromosome: the tip of the X chromosome of D.
RT   melanogaster.";
RL   Science 287:2220-2222(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   IDENTIFICATION IN THE TIP60 COMPLEX, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=15528408; DOI=10.1126/science.1103455;
RA   Kusch T., Florens L., Macdonald W.H., Swanson S.K., Glaser R.L.,
RA   Yates J.R. III, Abmayr S.M., Washburn M.P., Workman J.L.;
RT   "Acetylation by Tip60 is required for selective histone variant exchange at
RT   DNA lesions.";
RL   Science 306:2084-2087(2004).
CC   -!- FUNCTION: Catalytic subunit of the Tip60 chromatin-remodeling complex
CC       which is involved in DNA repair. Upon induction of DNA double-strand
CC       breaks, acetylates phosphorylated histone H2AV in nucleosomes on 'Lys-
CC       4' and exchanges it with unmodified H2AV.
CC       {ECO:0000269|PubMed:15528408}.
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:15528408};
CC   -!- SUBUNIT: Component of the Tip60 chromatin-remodeling complex which
CC       contains the catalytic subunit Tip60 and the subunits Domino, Tra1,
CC       Brd8, E(Pc), DMAP1, Pontin, Reptin, Ing3, Act87E, BAP55, Mrg15, MrgBP,
CC       Gas41 and YL-1. {ECO:0000269|PubMed:15528408}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15528408}.
CC   -!- PTM: Autoacetylation at Lys-355 is required for proper function.
CC       {ECO:0000250|UniProtKB:Q9H7Z6}.
CC   -!- SIMILARITY: Belongs to the MYST (SAS/MOZ) family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA21829.1; Type=Erroneous gene model prediction; Evidence={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; AE014298; AAF45923.3; -; Genomic_DNA.
DR   EMBL; AL033125; CAA21829.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AY051795; AAK93219.1; -; mRNA.
DR   RefSeq; NP_001259234.1; NM_001272305.1.
DR   RefSeq; NP_572151.1; NM_131923.4.
DR   AlphaFoldDB; Q960X4; -.
DR   SMR; Q960X4; -.
DR   BioGRID; 57879; 23.
DR   ComplexPortal; CPX-2264; NuA4 histone acetyltransferase complex.
DR   IntAct; Q960X4; 5.
DR   STRING; 7227.FBpp0070636; -.
DR   PaxDb; 7227-FBpp0070636; -.
DR   DNASU; 31362; -.
DR   EnsemblMetazoa; FBtr0070668; FBpp0070636; FBgn0026080.
DR   EnsemblMetazoa; FBtr0333186; FBpp0305388; FBgn0026080.
DR   GeneID; 31362; -.
DR   KEGG; dme:Dmel_CG6121; -.
DR   AGR; FB:FBgn0026080; -.
DR   CTD; 31362; -.
DR   FlyBase; FBgn0026080; Tip60.
DR   VEuPathDB; VectorBase:FBgn0026080; -.
DR   eggNOG; KOG2747; Eukaryota.
DR   GeneTree; ENSGT00940000163054; -.
DR   InParanoid; Q960X4; -.
DR   OMA; QYQRHGY; -.
DR   OrthoDB; 118560at2759; -.
DR   PhylomeDB; Q960X4; -.
DR   BRENDA; 2.3.1.48; 1994.
DR   Reactome; R-DME-201722; Formation of the beta-catenin:TCF transactivating complex.
DR   Reactome; R-DME-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR   Reactome; R-DME-5693548; Sensing of DNA Double Strand Breaks.
DR   Reactome; R-DME-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR   Reactome; R-DME-5693607; Processing of DNA double-strand break ends.
DR   Reactome; R-DME-9018519; Estrogen-dependent gene expression.
DR   BioGRID-ORCS; 31362; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; Tip60; fly.
DR   GenomeRNAi; 31362; -.
DR   PRO; PR:Q960X4; -.
DR   Proteomes; UP000000803; Chromosome X.
DR   Bgee; FBgn0026080; Expressed in egg cell and 25 other cell types or tissues.
DR   ExpressionAtlas; Q960X4; baseline and differential.
DR   GO; GO:0000123; C:histone acetyltransferase complex; IPI:FlyBase.
DR   GO; GO:0072487; C:MSL complex; IBA:GO_Central.
DR   GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR   GO; GO:0005705; C:polytene chromosome interband; IDA:FlyBase.
DR   GO; GO:1990188; F:euchromatin binding; IDA:FlyBase.
DR   GO; GO:0004402; F:histone acetyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0046972; F:histone H4K16 acetyltransferase activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR   GO; GO:0006338; P:chromatin remodeling; IMP:FlyBase.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0140861; P:DNA repair-dependent chromatin remodeling; IDA:FlyBase.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IBA:GO_Central.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:FlyBase.
DR   GO; GO:0007399; P:nervous system development; IMP:FlyBase.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:FlyBase.
DR   GO; GO:0048167; P:regulation of synaptic plasticity; IDA:FlyBase.
DR   GO; GO:2000331; P:regulation of terminal button organization; IDA:FlyBase.
DR   CDD; cd18985; CBD_TIP60_like; 1.
DR   CDD; cd04301; NAT_SF; 1.
DR   Gene3D; 2.30.30.140; -; 1.
DR   Gene3D; 3.40.630.30; -; 1.
DR   Gene3D; 3.30.60.60; N-acetyl transferase-like; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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; IPR025995; Tudor-knot.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR040706; Zf-MYST.
DR   PANTHER; PTHR10615; HISTONE ACETYLTRANSFERASE; 1.
DR   PANTHER; PTHR10615:SF161; HISTONE ACETYLTRANSFERASE KAT5; 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; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1.
DR   SUPFAM; SSF54160; Chromo domain-like; 1.
DR   PROSITE; PS51726; MYST_HAT; 1.
DR   Genevisible; Q960X4; DM.
PE   1: Evidence at protein level;
KW   Acetylation; Acyltransferase; Chromatin regulator; DNA damage; DNA repair;
KW   Metal-binding; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation; Transferase; Zinc; Zinc-finger.
FT   CHAIN           1..541
FT                   /note="Histone acetyltransferase Tip60"
FT                   /id="PRO_0000051583"
FT   DOMAIN          24..77
FT                   /note="Tudor-knot"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          255..533
FT                   /note="MYST-type HAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01063"
FT   ZN_FING         288..313
FT                   /note="C2HC MYST-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01063"
FT   REGION          82..162
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          178..251
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        84..118
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        186..213
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        232..251
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        431
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT   BINDING         398..400
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT   BINDING         405..411
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT   BINDING         435
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT   BINDING         444
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
FT   MOD_RES         355
FT                   /note="N6-acetyllysine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7Z6"
SQ   SEQUENCE   541 AA;  61234 MW;  F48A3415B708A97C CRC64;
     MKINHKYEFD DDVASICEST AALTEGCRLP VRMHKTDDWP LAEIVSIKEL DGRRQFYVHY
     VDFNKRLDEW VNEEDLYTRK VQFPRRDGSQ TGTSTGVTTP QRHHSLAGSV SRPTSPQHPG
     SGALAAIPQT PTGASGSVPP PAGIPNSVAP PGTPSSGGEL VNGNNLAAAL QKRINRKRKN
     HGGSAHGHHS LTSQQQQSHP HPTTPQTPTA TPVHVTGDGL ISGAANDDGD GSQDGKTPTP
     RQSGSMVTHQ DDVVTRMKNV EMIELGRHRI KPWYFSPYPQ ELCQMPCIYI CEFCLKYRKS
     RKCLERHLSK CNLRHPPGNE IYRKHTISFF EIDGRKNKVY AQNLCLLAKL FLDHKTLYYD
     TDPFLFYVMT EFDSRGFHIV GYFSKEKEST EDYNVACILT MPPYQRKGYG KLLIEFSYEL
     SKFEGKTGSP EKPLSDLGLL SYRSYWAQTI LEIFISQNPS TDGEKPTITI NDICECTSIK
     KEDVISTLQN LNLINYYKGQ YIVCINRVII EQHRRAMDKR KIRIDSKCLH WTPKDWSKRS
     K
//