SIRT1_DROME
ID SIRT1_DROME Reviewed; 823 AA.
AC Q9VK34; D5SHQ6; O96505;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=NAD-dependent histone deacetylase sirtuin-1 {ECO:0000312|FlyBase:FBgn0024291};
DE EC=2.3.1.286;
DE AltName: Full=Silent information regulator 2 {ECO:0000303|PubMed:12663533};
GN Name=Sirt1 {ECO:0000312|FlyBase:FBgn0024291};
GN Synonyms=Sir2 {ECO:0000303|PubMed:12663533};
GN ORFNames=CG5216 {ECO:0000312|FlyBase:FBgn0024291};
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 [MRNA], AND FUNCTION.
RX PubMed=12663533; DOI=10.1093/genetics/163.3.931;
RA Astrom S.U., Cline T.W., Rine J.;
RT "The Drosophila melanogaster sir2+ gene is nonessential and has only minor
RT effects on position-effect variegation.";
RL Genetics 163:931-937(2003).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.E.;
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11281647; DOI=10.1006/excr.2001.5162;
RA Barlow A.L., van Drunen C.M., Johnson C.A., Tweedie S., Bird A.,
RA Turner B.M.;
RT "dSIR2 and dHDAC6: two novel, inhibitor-resistant deacetylases in
RT Drosophila melanogaster.";
RL Exp. Cell Res. 265:90-103(2001).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH H AND DPN.
RX PubMed=12086602; DOI=10.1016/s0092-8674(02)00732-8;
RA Rosenberg M.I., Parkhurst S.M.;
RT "Drosophila Sir2 is required for heterochromatic silencing and by
RT euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex
RT determination.";
RL Cell 109:447-458(2002).
RN [7]
RP FUNCTION, AND INTERACTION WITH E(Z) AND HDAC1.
RX PubMed=15498488; DOI=10.1016/j.cub.2004.09.060;
RA Furuyama T., Banerjee R., Breen T.R., Harte P.J.;
RT "SIR2 is required for polycomb silencing and is associated with an E(Z)
RT histone methyltransferase complex.";
RL Curr. Biol. 14:1812-1821(2004).
RN [8]
RP FUNCTION.
RX PubMed=15520384; DOI=10.1073/pnas.0404184101;
RA Rogina B., Helfand S.L.;
RT "Sir2 mediates longevity in the fly through a pathway related to calorie
RT restriction.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15998-16003(2004).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17159295; DOI=10.1266/ggs.81.341;
RA Kusama S., Ueda R., Suda T., Nishihara S., Matsuura E.T.;
RT "Involvement of Drosophila Sir2-like genes in the regulation of life
RT span.";
RL Genes Genet. Syst. 81:341-348(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-618 AND SER-621, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: NAD-dependent histone deacetylase involved in heterochromatic
CC silencing. Mildly suppresses the heterochromatin-mediated silencing
CC phenomenon known as position-effect variegation (PEV). Required for
CC epigenetic silencing of the polycomb group proteins. Has histone H4
CC deacetylase activity in vitro. Required maternally for establishing
CC proper segmentation of the embryo. Involved in sex determination. May
CC be involved in the regulation of life span.
CC {ECO:0000269|PubMed:11281647, ECO:0000269|PubMed:12086602,
CC ECO:0000269|PubMed:12663533, ECO:0000269|PubMed:15498488,
CC ECO:0000269|PubMed:15520384, ECO:0000269|PubMed:17159295}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 9. {ECO:0000269|PubMed:11281647};
CC -!- SUBUNIT: Interacts with the transcriptional repressors hairy (h) and
CC deadpan (dpn); via basic domains. Associates with the Esc/E(z) histone
CC methyltransferase complex. Interacts directly with E(z) and HDAC1/Rpd3.
CC {ECO:0000269|PubMed:12086602, ECO:0000269|PubMed:15498488}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12086602}. Nucleus
CC {ECO:0000269|PubMed:11281647, ECO:0000269|PubMed:12086602}. Chromosome
CC {ECO:0000269|PubMed:12086602}.
CC -!- DISRUPTION PHENOTYPE: Causes lethality during development. Induced
CC silencing shortens life span. {ECO:0000269|PubMed:17159295}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; AF068758; AAC79684.1; -; mRNA.
DR EMBL; AE014134; AAF53248.1; -; Genomic_DNA.
DR EMBL; BT124857; ADG03442.1; -; mRNA.
DR EMBL; BT133215; AFA28456.1; -; mRNA.
DR EMBL; BT133274; AFC38905.1; -; mRNA.
DR RefSeq; NP_477351.1; NM_058003.4.
DR AlphaFoldDB; Q9VK34; -.
DR SMR; Q9VK34; -.
DR BioGRID; 60746; 40.
DR IntAct; Q9VK34; 5.
DR STRING; 7227.FBpp0080015; -.
DR iPTMnet; Q9VK34; -.
DR PaxDb; Q9VK34; -.
DR EnsemblMetazoa; FBtr0080434; FBpp0080015; FBgn0024291.
DR GeneID; 34708; -.
DR KEGG; dme:Dmel_CG5216; -.
DR UCSC; CG5216-RA; d. melanogaster.
DR CTD; 23411; -.
DR FlyBase; FBgn0024291; Sirt1.
DR VEuPathDB; VectorBase:FBgn0024291; -.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000159406; -.
DR HOGENOM; CLU_016587_1_0_1; -.
DR InParanoid; Q9VK34; -.
DR OMA; NGIMKPD; -.
DR OrthoDB; 973532at2759; -.
DR PhylomeDB; Q9VK34; -.
DR BRENDA; 2.3.1.286; 1994.
DR Reactome; R-DME-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-DME-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR SignaLink; Q9VK34; -.
DR BioGRID-ORCS; 34708; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Sirt1; fly.
DR GenomeRNAi; 34708; -.
DR PRO; PR:Q9VK34; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0024291; Expressed in cleaving embryo and 26 other tissues.
DR ExpressionAtlas; Q9VK34; baseline and differential.
DR Genevisible; Q9VK34; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005637; C:nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0033553; C:rDNA heterochromatin; IBA:GO_Central.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:FlyBase.
DR GO; GO:0002039; F:p53 binding; IBA:GO_Central.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:FlyBase.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0008134; F:transcription factor binding; IPI:FlyBase.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:FlyBase.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0031507; P:heterochromatin assembly; IMP:FlyBase.
DR GO; GO:0016575; P:histone deacetylation; IDA:FlyBase.
DR GO; GO:0070932; P:histone H3 deacetylation; IBA:GO_Central.
DR GO; GO:0046331; P:lateral inhibition; IMP:FlyBase.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:FlyBase.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IMP:FlyBase.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IMP:FlyBase.
DR GO; GO:0006476; P:protein deacetylation; IMP:FlyBase.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0035065; P:regulation of histone acetylation; IMP:FlyBase.
DR GO; GO:1901416; P:regulation of response to ethanol; IMP:FlyBase.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:FlyBase.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Chromosome; Cytoplasm; Metal-binding; NAD; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Transferase; Zinc.
FT CHAIN 1..823
FT /note="NAD-dependent histone deacetylase sirtuin-1"
FT /id="PRO_0000417405"
FT DOMAIN 212..485
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 41..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 698..722
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 777..823
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..103
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..131
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..146
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 706..722
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 790..808
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 229..248
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 313..316
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 342
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 363
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 366
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 427..429
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 452..454
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 469
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 618
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 53..54
FT /note="Missing (in Ref. 1; AAC79684)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="E -> K (in Ref. 4; ADG03442)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="Q -> QFQ (in Ref. 1; AAC79684)"
FT /evidence="ECO:0000305"
FT CONFLICT 518
FT /note="L -> H (in Ref. 1; AAC79684)"
FT /evidence="ECO:0000305"
FT CONFLICT 746
FT /note="P -> H (in Ref. 1; AAC79684)"
FT /evidence="ECO:0000305"
FT CONFLICT 753
FT /note="V -> F (in Ref. 1; AAC79684)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 823 AA; 91837 MW; 3DD1EBA975A263D3 CRC64;
MMENYEEIRL GHIRSKDLGN QVPDTTQFYP PTKFDFGAEI LASTSTEAEA EAEATATTTE
PATSELAGKA NGEIKTKTLA AREEQEIGAN LEHKTKNPTK SMGEDEDDEE EEEEDDEEEE
EDDEEGITGT SNEDEDSSSN CSSSVEPDWK LRWLQREFYT GRVPRQVIAS IMPHFATGLA
GDTDDSVLWD YLAHLLNEPK RRNKLASVNT FDDVISLVKK SQKIIVLTGA GVSVSCGIPD
FRSTNGIYAR LAHDFPDLPD PQAMFDINYF KRDPRPFYKF AREIYPGEFQ PSPCHRFIKM
LETKGKLLRN YTQNIDTLER VAGIQRVIEC HGSFSTASCT KCRFKCNADA LRADIFAQRI
PVCPQCQPNK EQSVDASVAV TEEELRQLVE NGIMKPDIVF FGEGLPDEYH TVMATDKDVC
DLLIVIGSSL KVRPVAHIPS SIPATVPQIL INREQLHHLK FDVELLGDSD VIINQICHRL
SDNDDCWRQL CCDESVLTES KELMPPEHSN HHLHHHLLHH RHCSSESERQ SQLDTDTQSI
KSNSSADYIL GSAGTCSDSG FESSTFSCGK RSTAAEAAAI ERIKTDILVE LNETTALSCD
RLGLEGPQTT VESYRHLSID SSKDSGIEQC DNEATPSYVR PSNLVQETKT VAPSLTPIPQ
QRGKRQTAAE RLQPGTFYSH TNNYSYVFPG AQVFWDNDYS DDDDEEEERS HNRHSDLFGN
VGHNYKDDDE DACDLNAVPL SPLLPPSLEA HIVTDIVNGS NEPLPNSSPG QKRTACIIEQ
QPTPAIETEI PPLKKRRPSE ENKQQTQIER SEESPPPGQL AAV
