ID Q59E49_DROME Unreviewed; 1203 AA. AC Q59E49; DT 26-APR-2005, integrated into UniProtKB/TrEMBL. DT 30-NOV-2010, sequence version 2. DT 27-MAR-2024, entry version 153. DE RecName: Full=Histone deacetylase {ECO:0000256|PIRNR:PIRNR037911}; DE EC=3.5.1.98 {ECO:0000256|PIRNR:PIRNR037911}; GN Name=HDAC4 {ECO:0000313|EMBL:AAX52490.2, GN ECO:0000313|FlyBase:FBgn0041210}; GN Synonyms=DHDAC4 {ECO:0000313|EMBL:AAX52490.2}, dHDAC4 GN {ECO:0000313|EMBL:AAX52490.2}, Dmel\CG1770 GN {ECO:0000313|EMBL:AAX52490.2}, dmHDA405 {ECO:0000313|EMBL:AAX52490.2}, GN GC1770 {ECO:0000313|EMBL:AAX52490.2}, HDAC GN {ECO:0000313|EMBL:AAX52490.2}, hdac4 {ECO:0000313|EMBL:AAX52490.2}, GN HDAC4a {ECO:0000313|EMBL:AAX52490.2}; GN ORFNames=CG1770 {ECO:0000313|EMBL:AAX52490.2, GN ECO:0000313|FlyBase:FBgn0041210}, Dmel_CG1770 GN {ECO:0000313|EMBL:AAX52490.2}; 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 {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803}; RN [1] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; 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., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Gabor G.L., 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., 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., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J., 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., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T., Spier E., RA Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., RA Turner R., Venter E., Wang A.H., Wang X., Wang Z.Y., Wassarman D.A., RA Weinstock G.M., Weissenbach J., Williams S.M., WoodageT, Worley K.C., RA Wu D., Yang S., Yao Q.A., Ye J., Yeh R.F., Zaveri J.S., Zhan M., Zhang G., RA Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S., RA Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [2] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=12537568; RA Celniker S.E., Wheeler D.A., Kronmiller B., Carlson J.W., Halpern A., RA Patel S., Adams M., Champe M., Dugan S.P., Frise E., Hodgson A., RA George R.A., Hoskins R.A., Laverty T., Muzny D.M., Nelson C.R., RA Pacleb J.M., Park S., Pfeiffer B.D., Richards S., Sodergren E.J., RA Svirskas R., Tabor P.E., Wan K., Stapleton M., Sutton G.G., Venter C., RA Weinstock G., Scherer S.E., Myers E.W., Gibbs R.A., Rubin G.M.; RT "Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster RT euchromatic genome sequence."; RL Genome Biol. 3:RESEARCH0079-RESEARCH0079(2002). RN [3] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP GENOME REANNOTATION. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; 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 [4] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=12537573; RA Kaminker J.S., Bergman C.M., Kronmiller B., Carlson J., Svirskas R., RA Patel S., Frise E., Wheeler D.A., Lewis S.E., Rubin G.M., Ashburner M., RA Celniker S.E.; RT "The transposable elements of the Drosophila melanogaster euchromatin: a RT genomics perspective."; RL Genome Biol. 3:RESEARCH0084.1-RESEARCH0084.20(2002). RN [5] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=12537574; RA Hoskins R.A., Smith C.D., Carlson J.W., Carvalho A.B., Halpern A., RA Kaminker J.S., Kennedy C., Mungall C.J., Sullivan B.A., Sutton G.G., RA Yasuhara J.C., Wakimoto B.T., Myers E.W., Celniker S.E., Rubin G.M., RA Karpen G.H.; RT "Heterochromatic sequences in a Drosophila whole-genome shotgun assembly."; RL Genome Biol. 3:RESEARCH0085-RESEARCH0085(2002). RN [6] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=16110336; DOI=10.1371/journal.pcbi.0010022; RA Quesneville H., Bergman C.M., Andrieu O., Autard D., Nouaud D., RA Ashburner M., Anxolabehere D.; RT "Combined evidence annotation of transposable elements in genome RT sequences."; RL PLoS Comput. Biol. 1:166-175(2005). RN [7] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=17569856; DOI=10.1126/science.1139815; RA Smith C.D., Shu S., Mungall C.J., Karpen G.H.; RT "The Release 5.1 annotation of Drosophila melanogaster heterochromatin."; RL Science 316:1586-1591(2007). RN [8] {ECO:0000313|EMBL:AAX52490.2, ECO:0000313|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803}; RX PubMed=17569867; DOI=10.1126/science.1139816; RA Hoskins R.A., Carlson J.W., Kennedy C., Acevedo D., Evans-Holm M., RA Frise E., Wan K.H., Park S., Mendez-Lago M., Rossi F., Villasante A., RA Dimitri P., Karpen G.H., Celniker S.E.; RT "Sequence finishing and mapping of Drosophila melanogaster RT heterochromatin."; RL Science 316:1625-1628(2007). CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on the CC N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone CC deacetylation gives a tag for epigenetic repression and plays an CC important role in transcriptional regulation, cell cycle progression CC and developmental events. {ECO:0000256|PIRNR:PIRNR037911}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl- CC [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA- CC COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089, CC ChEBI:CHEBI:61930; EC=3.5.1.98; CC Evidence={ECO:0000256|ARBA:ARBA00001028, CC ECO:0000256|PIRNR:PIRNR037911}; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|PIRNR:PIRNR037911}. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2 CC subfamily. {ECO:0000256|ARBA:ARBA00007738, CC ECO:0000256|PIRNR:PIRNR037911}. 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; AAX52490.2; -; Genomic_DNA. DR RefSeq; NP_001014736.2; NM_001014736.5. DR AlphaFoldDB; Q59E49; -. DR SMR; Q59E49; -. DR EnsemblMetazoa; FBtr0301299; FBpp0290514; FBgn0041210. DR GeneID; 32278; -. DR KEGG; dme:Dmel_CG1770; -. DR UCSC; CG1770-RC; d. melanogaster. DR AGR; FB:FBgn0041210; -. DR CTD; 9759; -. DR FlyBase; FBgn0041210; HDAC4. DR VEuPathDB; VectorBase:FBgn0041210; -. DR GeneTree; ENSGT00940000169192; -. DR OrthoDB; 124800at2759; -. DR BioGRID-ORCS; 32278; 0 hits in 3 CRISPR screens. DR ChiTaRS; HDAC4; fly. DR GenomeRNAi; 32278; -. DR Proteomes; UP000000803; Chromosome X. DR Bgee; FBgn0041210; Expressed in brain and 20 other cell types or tissues. DR ExpressionAtlas; Q59E49; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase. DR GO; GO:0000118; C:histone deacetylase complex; IEA:UniProtKB-UniRule. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0004407; F:histone deacetylase activity; IDA:FlyBase. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0007616; P:long-term memory; IMP:FlyBase. DR GO; GO:0007613; P:memory; IMP:FlyBase. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:InterPro. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:FlyBase. DR CDD; cd11681; HDAC_classIIa; 1. DR Gene3D; 3.40.800.20; Histone deacetylase domain; 1. DR InterPro; IPR046949; HDAC4/5/7/9. DR InterPro; IPR000286; His_deacetylse. DR InterPro; IPR023801; His_deacetylse_dom. DR InterPro; IPR037138; His_deacetylse_dom_sf. DR InterPro; IPR023696; Ureohydrolase_dom_sf. DR PANTHER; PTHR10625:SF15; HISTONE DEACETYLASE; 1. DR PANTHER; PTHR10625; HISTONE DEACETYLASE HDAC1-RELATED; 1. DR Pfam; PF00850; Hist_deacetyl; 1. DR PIRSF; PIRSF037911; HDAC_II_euk; 4. DR PRINTS; PR01270; HDASUPER. DR SUPFAM; SSF52768; Arginase/deacetylase; 1. DR Genevisible; Q59E49; DM. PE 1: Evidence at protein level; KW Chromatin regulator {ECO:0000256|PIRNR:PIRNR037911}; KW Coiled coil {ECO:0000256|SAM:Coils}; KW Hydrolase {ECO:0000256|PIRNR:PIRNR037911, ECO:0000313|EMBL:AAX52490.2}; KW Metal-binding {ECO:0000256|PIRSR:PIRSR037911-2}; KW Proteomics identification {ECO:0007829|PeptideAtlas:Q59E49}; KW Reference proteome {ECO:0000313|Proteomes:UP000000803}; KW Repressor {ECO:0000256|PIRNR:PIRNR037911}; KW Transcription {ECO:0000256|PIRNR:PIRNR037911}; KW Transcription regulation {ECO:0000256|PIRNR:PIRNR037911}; KW Zinc {ECO:0000256|PIRSR:PIRSR037911-2}. FT DOMAIN 794..1109 FT /note="Histone deacetylase" FT /evidence="ECO:0000259|Pfam:PF00850" FT REGION 114..151 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 178..296 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 458..489 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1182..1203 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 540..567 FT /evidence="ECO:0000256|SAM:Coils" FT COMPBIAS 178..208 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 235..249 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 266..296 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 470..489 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1187..1203 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 919 FT /evidence="ECO:0000256|PIRSR:PIRSR037911-1" FT BINDING 786 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000256|PIRSR:PIRSR037911-2" FT BINDING 788 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000256|PIRSR:PIRSR037911-2" FT BINDING 794 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000256|PIRSR:PIRSR037911-2" FT BINDING 867 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000256|PIRSR:PIRSR037911-2" SQ SEQUENCE 1203 AA; 128636 MW; C41E58855E15AC44 CRC64; MSSPDDRIPI HDLPSEAGSD ERLLHITPAT LTLDFKPHPA VDIDQQIMEL KKSQELQKQR LINSFQEQSK QMELEHKLQL EHKYQFAVNS HGAFQELRNE SMVTAAAAAV AQEQHRQQLH QQQQQHQQQQ QQQQHQQQQQ QQQARGRDGM KLKQNCSANA SPEVKQILNC FILSRKSQAA ASNGTTTTSP YRNRGVVKSS SGESLPAGTV TSAHPYKIPQ PPPSLLKYES DFPLRKTDCN STPDSGPNSP PSAAALAVGV VGSRGSPTSA PIQEENEEGS QYQPGQRSSI NDLPLFSSPS LPNISLGRPH LPNSAQAHAQ VNAQVAAQAQ AQAQAQAQAH AMFAALAAAQ GGCGQPGYYN PLGMAFVGRQ PAPLAMIPAT GIAPQQPSPV VRSASATSTS SSQASLVGDV APPQAHAAST ILPSSSSYMQ QLGSVAGSGV NLHAAAVAAA AAAAAAAGSL PPTNSHGHGH GSHAHPHPHA HGHGHGHGHG IYAGHQHNVP ITDAQVAQVH LHKQGHRPLG RTQSAPLPLG HPMLTGAVQL NVVQTHYENS EAERQAYEHQ VVNQKVRQTV LTRSGAAAAA AAAAGVSVVR EAQLKEEDDD SAAEVMDLTD KKKPPKTVLT STIATSTSQN LPEALAAAAA AAAYRAPHNA SSNSASATKS GIKLRDQEYL QQQREQLLLL QQEEELAKSL MRPLSRTLSS PLVPLGPHGL SQIPDTGQQP APIATSSSAD HIPPVNLSLP HRQHRQLMST LYASQLRNHQ PSASGSPPHK VTTGLAYDPL MLKHSCICGD NAQHPEHSGR LQSVWARLNE TDLVKRCDRL RARKATQEEL QTVHTEAHAM LFGSNQCQLS RPKLENTLSA SFVRLSCGGL GVDLDTTWNE HHTATAARMA AGCVIDLALK TAKGDLRNGF AVVRPPGHHA EANLAMGFCF FNSIAIAAKL LRQRMPEVRR ILIVDWDVHH GNGTQQAFYQ SPDILYLSIH RHDDGNFFPG TGGPTECGSG AGLGFNVNIS WSGALNPPLG DAEYIAAFRT VVMPIARSFN PDIVLVSSGF DAATGHPAPL GGYHVSPACF GFMTRELLQL ANGKVVLALE GGYDLAAICD SAQECVRALL GDPAAPIAKA ELERPPCQNA INTLQKTIAI QQTHWPCVRM LEHTVGLSAL ETLKVEHDES ETINAMAGLS MQSMHRTLSR DDSEEPMDQD ETK //