SIR6_DROME
ID SIR6_DROME Reviewed; 317 AA.
AC Q9VH08; F3YD73;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=NAD-dependent protein deacetylase Sirt6 {ECO:0000305};
DE EC=2.3.1.286 {ECO:0000255|PROSITE-ProRule:PRU00236, ECO:0000269|PubMed:35091469};
DE AltName: Full=Regulatory protein SIR2 homolog 6 {ECO:0000305};
DE Short=dSirt6 {ECO:0000303|PubMed:35091469};
DE AltName: Full=SIR2-like protein 6;
GN Name=Sirt6 {ECO:0000303|PubMed:35091469, ECO:0000312|FlyBase:FBgn0037802};
GN ORFNames=CG6284 {ECO:0000312|FlyBase:FBgn0037802};
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 MRNA].
RA Carlson J., Booth B., Frise E., Sandler J., Wan K., Yu C., Celniker S.E.;
RL Submitted (APR-2011) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=35091469; DOI=10.1073/pnas.2111176119;
RA Taylor J.R., Wood J.G., Mizerak E., Hinthorn S., Liu J., Finn M.,
RA Gordon S., Zingas L., Chang C., Klein M.A., Denu J.M., Gorbunova V.,
RA Seluanov A., Boeke J.D., Sedivy J.M., Helfand S.L.;
RT "Sirt6 regulates lifespan in Drosophila melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 119:0-0(2022).
CC -!- FUNCTION: NAD-dependent histone deacylase that acts as a regulator of
CC life span. {ECO:0000269|PubMed:17159295, ECO:0000269|PubMed:35091469}.
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 ECO:0000269|PubMed:35091469};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q8N6T7};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8N6T7};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:35091469}. Chromosome
CC {ECO:0000269|PubMed:35091469}. Note=Predominantly nuclear; associated
CC with chromatin. {ECO:0000269|PubMed:35091469}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:35091469}.
CC -!- DISRUPTION PHENOTYPE: Causes lethality during development
CC (PubMed:17159295). Induced silencing shortens life span
CC (PubMed:17159295). {ECO:0000269|PubMed:17159295}.
CC -!- MISCELLANEOUS: Overexpression in flies produces robust lifespan
CC extension in both sexes. {ECO:0000269|PubMed:35091469}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class IV subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF54513.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AEB33520.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAF54513.2; ALT_SEQ; Genomic_DNA.
DR EMBL; BT126234; AEB33520.1; ALT_INIT; mRNA.
DR RefSeq; NP_649990.2; NM_141733.3.
DR AlphaFoldDB; Q9VH08; -.
DR SMR; Q9VH08; -.
DR BioGRID; 66403; 3.
DR STRING; 7227.FBpp0293897; -.
DR PaxDb; Q9VH08; -.
DR PRIDE; Q9VH08; -.
DR EnsemblMetazoa; FBtr0305358; FBpp0293897; FBgn0037802.
DR GeneID; 41254; -.
DR KEGG; dme:Dmel_CG6284; -.
DR UCSC; CG6284-RA; d. melanogaster.
DR CTD; 51548; -.
DR FlyBase; FBgn0037802; Sirt6.
DR VEuPathDB; VectorBase:FBgn0037802; -.
DR eggNOG; KOG1905; Eukaryota.
DR GeneTree; ENSGT00940000160088; -.
DR HOGENOM; CLU_023643_6_0_1; -.
DR InParanoid; Q9VH08; -.
DR OrthoDB; 1503290at2759; -.
DR PhylomeDB; Q9VH08; -.
DR BioGRID-ORCS; 41254; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Sirt6; fly.
DR GenomeRNAi; 41254; -.
DR PRO; PR:Q9VH08; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037802; Expressed in adult abdomen and 22 other tissues.
DR Genevisible; Q9VH08; DM.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0019213; F:deacetylase activity; IBA:GO_Central.
DR GO; GO:0004407; F:histone deacetylase activity; IMP:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; NAS:FlyBase.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0008340; P:determination of adult lifespan; IDA:UniProtKB.
DR GO; GO:0016575; P:histone deacetylation; IMP:FlyBase.
DR GO; GO:0070932; P:histone H3 deacetylation; IBA:GO_Central.
DR GO; GO:0090310; P:negative regulation of DNA methylation-dependent heterochromatin assembly; IMP:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 2.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Chromatin regulator; Chromosome; Metal-binding; NAD;
KW Nucleus; Reference proteome; Transferase; Zinc.
FT CHAIN 1..317
FT /note="NAD-dependent protein deacetylase Sirt6"
FT /id="PRO_0000417362"
FT DOMAIN 35..275
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT ACT_SITE 133
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 53
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 64
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 65
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 71
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 113
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 133
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 215
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 241
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 243
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 259
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
SQ SEQUENCE 317 AA; 35204 MW; 660B59F0EB3E3BAC CRC64;
MSCNYADGLS AYDNKGILGA PESFDSDEVV AEKCQELAEL IKKSGHVVLH TGAGISTSAG
IPDFRGPKGV WTLEEKGEKP DFNVSFDEAR PTKTHMAIIA LIESGYVQYV ISQNIDGLHL
KSGLDRKYLS ELHGNIYIEQ CKKCRRQFVS PSAVETVGQK SLQRACKSSM DSKGRSCRSG
ILYDNVLDWE HDLPENDLEM GVMHSTVADL NIALGTTLQI VPSGDLPLKN LKCGGKFVIC
NLQPTKHDKK ANLIISSYVD VVLSKVCKLL GVEIPEYSEA SDPTKQSKPM EWTIPTSNVN
TFHRQYKKYV YFIYYLL
