TIP60_DROME
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 03-AUG-2022, entry version 173.
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, ECO:0000312|FlyBase:FBgn0026080};
GN 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 IntAct; Q960X4; 5.
DR STRING; 7227.FBpp0070636; -.
DR PaxDb; Q960X4; -.
DR PRIDE; Q960X4; -.
DR DNASU; 31362; -.
DR EnsemblMetazoa; FBtr0070668; FBpp0070636; FBgn0026080.
DR EnsemblMetazoa; FBtr0333186; FBpp0305388; FBgn0026080.
DR GeneID; 31362; -.
DR KEGG; dme:Dmel_CG6121; -.
DR CTD; 31362; -.
DR FlyBase; FBgn0026080; Tip60.
DR VEuPathDB; VectorBase:FBgn0026080; -.
DR eggNOG; KOG2747; Eukaryota.
DR GeneTree; ENSGT00940000163054; -.
DR InParanoid; Q960X4; -.
DR OMA; SMTQNQT; -.
DR OrthoDB; 629545at2759; -.
DR PhylomeDB; Q960X4; -.
DR BRENDA; 2.3.1.48; 1994.
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-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-DME-69473; G2/M DNA damage checkpoint.
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 tissues.
DR ExpressionAtlas; Q960X4; baseline and differential.
DR Genevisible; Q960X4; DM.
DR GO; GO:0000123; C:histone acetyltransferase complex; IPI:FlyBase.
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:0042393; F:histone binding; 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:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0016573; P:histone acetylation; IDA:UniProtKB.
DR GO; GO:0043486; P:histone exchange; IDA:UniProtKB.
DR GO; GO:0043967; P:histone H4 acetylation; IMP:FlyBase.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:FlyBase.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
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 GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:FlyBase.
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; 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
