ID SIR2_SCHPO Reviewed; 475 AA.
AC O94640; Q6H8I3;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 27-MAR-2024, entry version 161.
DE RecName: Full=NAD-dependent histone deacetylase sir2;
DE EC=2.3.1.286 {ECO:0000255|PROSITE-ProRule:PRU00236};
DE AltName: Full=Regulatory protein sir2;
DE AltName: Full=Silent information regulator 2;
GN Name=sir2; ORFNames=SPBC16D10.07c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15545655; DOI=10.1534/genetics.104.032714;
RA Freeman-Cook L.L., Gomez E.B., Spedale E.J., Marlett J., Forsburg S.L.,
RA Pillus L., Laurenson P.;
RT "Conserved locus-specific silencing functions of Schizosaccharomyces pombe
RT sir2+.";
RL Genetics 169:1243-1260(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP SEQUENCE REVISION.
RA Wood V., Rajandream M.A., Barrell B.G., Brown D., Churcher C.M.;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=12867036; DOI=10.1016/s0960-9822(03)00489-5;
RA Shankaranarayana G.D., Motamedi M.R., Moazed D., Grewal S.I.S.;
RT "Sir2 regulates histone H3 lysine 9 methylation and heterochromatin
RT assembly in fission yeast.";
RL Curr. Biol. 13:1240-1246(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
CC -!- FUNCTION: Involved in silencing within the mating-type region, at the
CC telomeres, and according to PubMed:12867036 also within centromeric DNA
CC regions. Required for the localization of swi6 to the telomeres, silent
CC mating type region, and according to PubMed:12867036 to the centromeric
CC DNA regions. According to PubMed:15545655 not required for the
CC localization of swi6 to centromeric foci. Deacetylates histone H3 on
CC 'Lys-9' and 'Lys-16' of histone H4. This has a direct role in
CC heterochromatin assembly. {ECO:0000269|PubMed:12867036,
CC ECO:0000269|PubMed:15545655}.
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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15545655}.
CC Chromosome, centromere {ECO:0000269|PubMed:15545655}. Chromosome,
CC telomere {ECO:0000269|PubMed:15545655}. Note=Nuclear throughout the
CC cell cycle. Binds to centromeres, telomeric sites and sites between the
CC silent mating-type loci.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {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; CU329671; CAG47122.1; -; Genomic_DNA.
DR PIR; T39571; T39571.
DR RefSeq; NP_001018840.1; NM_001022423.2.
DR AlphaFoldDB; O94640; -.
DR SMR; O94640; -.
DR BioGRID; 280418; 62.
DR IntAct; O94640; 1.
DR STRING; 284812.O94640; -.
DR iPTMnet; O94640; -.
DR SwissPalm; O94640; -.
DR MaxQB; O94640; -.
DR PaxDb; 4896-SPBC16D10-07c-1; -.
DR EnsemblFungi; SPBC16D10.07c.1; SPBC16D10.07c.1:pep; SPBC16D10.07c.
DR GeneID; 3361342; -.
DR KEGG; spo:SPBC16D10.07c; -.
DR PomBase; SPBC16D10.07c; sir2.
DR VEuPathDB; FungiDB:SPBC16D10.07c; -.
DR eggNOG; KOG2684; Eukaryota.
DR HOGENOM; CLU_023643_5_3_1; -.
DR InParanoid; O94640; -.
DR OMA; PTHEFIR; -.
DR PhylomeDB; O94640; -.
DR Reactome; R-SPO-3371453; Regulation of HSF1-mediated heat shock response.
DR PRO; PR:O94640; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0000785; C:chromatin; IDA:PomBase.
DR GO; GO:0099115; C:chromosome, subtelomeric region; IDA:PomBase.
DR GO; GO:0031934; C:mating-type region heterochromatin; IDA:PomBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005721; C:pericentric heterochromatin; IDA:PomBase.
DR GO; GO:0033553; C:rDNA heterochromatin; IDA:PomBase.
DR GO; GO:0034967; C:Set3 complex; ISO:PomBase.
DR GO; GO:0140720; C:subtelomeric heterochromatin; EXP:PomBase.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB.
DR GO; GO:0031078; F:histone H3K14 deacetylase activity; IDA:PomBase.
DR GO; GO:1990162; F:histone H3K4 deacetylase activity; IDA:PomBase.
DR GO; GO:0032129; F:histone H3K9 deacetylase activity; IDA:PomBase.
DR GO; GO:0034739; F:histone H4K16 deacetylase activity; IDA:PomBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IDA:PomBase.
DR GO; GO:0046969; F:NAD-dependent histone H3K9 deacetylase activity; IDA:PomBase.
DR GO; GO:0046970; F:NAD-dependent histone H4K16 deacetylase activity; IDA:PomBase.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0040029; P:epigenetic regulation of gene expression; IMP:PomBase.
DR GO; GO:0031507; P:heterochromatin formation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEP:PomBase.
DR CDD; cd01408; SIRT1; 1.
DR Gene3D; 3.30.1600.10; SIR2/SIRT2 'Small Domain; 1.
DR Gene3D; 3.40.50.1220; TPP-binding domain; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR007654; NAD-dep_histone_deAcase_SIR2_N.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR PANTHER; PTHR11085:SF14; NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-1; 1.
DR PANTHER; PTHR11085; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1.
DR Pfam; PF04574; DUF592; 1.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Centromere; Chromatin regulator; Chromosome; DNA damage; DNA repair;
KW Metal-binding; NAD; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Telomere; Transcription; Transcription regulation; Transferase; Zinc.
FT CHAIN 1..475
FT /note="NAD-dependent histone deacetylase sir2"
FT /id="PRO_0000110279"
FT DOMAIN 139..436
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 266
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 164..183
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 246..249
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 274
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 298
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 301
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 373..375
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 398..400
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 416
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
SQ SEQUENCE 475 AA; 53442 MW; 2C078420B5CEE4F9 CRC64;
MASNPLDNNM PTTPVEEKIP VASYSPSSSG SSSGASLLVD IMCGSKETED EEVDSDEWDK
PETENISDLD ERSEMVRYLR ASGYAKFLEK YLIEEELPVR SILKKLGINL PSALEEFEDI
DLLPLLKEVL KREVARRIKL PHFNTFEDVV NLLKKAKNVV VLVGAGISTS LGILDFRSDN
GFYARLARHG LSEPSEMFDI HTFRENPEIF YTFARDLLPE TNHYSPSHAF IRLLEKKNKL
STLFTQNIDN LEKKTGLSDN KIIQCHGSFA TATCIKCKHK VDGSELYEDI RNQRVSYCNE
CGKPPLKLRR VGQNKKEKHY FSDGDSESSE DDLAQPGIMK PDITFFGEAL PDSFFNKVGS
GELEETDLLI CIGTSLKVAP VSELISVIPP TTPQIYISRT PVRHTQFDVN FLSPYCDWVI
VEICKRAGWL NELQALCDLP ECHSGSKTRA FETDLDIKFE EPSTYHITST TNGSC
//
