SIR2_CAEBR
ID SIR2_CAEBR Reviewed; 602 AA.
AC Q60L58; A8WJ80;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=NAD-dependent protein deacetylase sir-2.1;
DE EC=2.3.1.286;
DE AltName: Full=Protein sir-2.1;
DE AltName: Full=Regulatory protein SIR2 homolog 1;
GN Name=sir-2.1; ORFNames=CBG23756;
OS Caenorhabditis briggsae.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6238;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AF16;
RX PubMed=14624247; DOI=10.1371/journal.pbio.0000045;
RA Stein L.D., Bao Z., Blasiar D., Blumenthal T., Brent M.R., Chen N.,
RA Chinwalla A., Clarke L., Clee C., Coghlan A., Coulson A., D'Eustachio P.,
RA Fitch D.H.A., Fulton L.A., Fulton R.E., Griffiths-Jones S., Harris T.W.,
RA Hillier L.W., Kamath R., Kuwabara P.E., Mardis E.R., Marra M.A.,
RA Miner T.L., Minx P., Mullikin J.C., Plumb R.W., Rogers J., Schein J.E.,
RA Sohrmann M., Spieth J., Stajich J.E., Wei C., Willey D., Wilson R.K.,
RA Durbin R.M., Waterston R.H.;
RT "The genome sequence of Caenorhabditis briggsae: a platform for comparative
RT genomics.";
RL PLoS Biol. 1:166-192(2003).
CC -!- FUNCTION: NAD-dependent deacetylase. Required for a reduction of the
CC 'Lys-16' acetylation of histone H4 (H4K16ac) on dosage-compensated X
CC chromosomes in hermaphrodites. Functions upstream of daf-16 in the
CC insulin-like signaling pathway, promoting daf-16 mediated
CC transcriptional activation and increased life-span. May also regulate
CC life-span independently of daf-16 by modulating the transcription of
CC genes involved in the stress response of the endoplasmic reticulum
CC (ER). Acts upstream of the nicotinic acid metabolism pathway, which may
CC be linked to the regulation of longevity. Plays a role in ascaroside-
CC mediated longevity and stress resistance.
CC {ECO:0000250|UniProtKB:Q21921}.
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;
CC Evidence={ECO:0000250|UniProtKB:P06700};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P06700};
CC -!- SUBUNIT: Interacts with ftt-2 and par-5. Interacts with daf-16
CC following heat-shock, which causes daf-16 to accumulate in the nucleus.
CC Interaction with daf-16 is promoted by ftt-2.
CC {ECO:0000250|UniProtKB:Q21921}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q21921}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; HE601379; CAP20522.3; -; Genomic_DNA.
DR RefSeq; XP_002647890.1; XM_002647844.1.
DR AlphaFoldDB; Q60L58; -.
DR SMR; Q60L58; -.
DR STRING; 6238.CBG23756; -.
DR EnsemblMetazoa; CBG23756.1; CBG23756.1; WBGene00042025.
DR GeneID; 8589890; -.
DR KEGG; cbr:CBG_23756; -.
DR CTD; 8589890; -.
DR WormBase; CBG23756; CBP24538; WBGene00042025; Cbr-sir-2.1.
DR eggNOG; KOG2684; Eukaryota.
DR HOGENOM; CLU_016587_1_0_1; -.
DR InParanoid; Q60L58; -.
DR OMA; FSKCTCT; -.
DR OrthoDB; 973532at2759; -.
DR Proteomes; UP000008549; Unassembled WGS sequence.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:EnsemblMetazoa.
DR GO; GO:0005637; C:nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:EnsemblMetazoa.
DR GO; GO:0033553; C:rDNA heterochromatin; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0002039; F:p53 binding; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0040024; P:dauer larval development; IEA:EnsemblMetazoa.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:EnsemblMetazoa.
DR GO; GO:0070932; P:histone H3 deacetylation; IBA:GO_Central.
DR GO; GO:0043970; P:histone H3-K9 acetylation; IEA:EnsemblMetazoa.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:EnsemblMetazoa.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
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 3: Inferred from homology;
KW Metal-binding; NAD; Nucleus; Reference proteome; Transferase; Zinc.
FT CHAIN 1..602
FT /note="NAD-dependent protein deacetylase sir-2.1"
FT /id="PRO_0000249598"
FT DOMAIN 127..376
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 25..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 411..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 520..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..437
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 451..468
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 528..551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 246
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 144..163
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P06700"
FT BINDING 228..231
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P53686"
FT BINDING 254
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 278
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 281
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 318..320
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P06700"
FT BINDING 343..345
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P06700"
FT BINDING 360
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P06700"
SQ SEQUENCE 602 AA; 68414 MW; 283BD589276D92C0 CRC64;
MSHESHHSEG MATSGEVHEI REEEPEIETM HIENSVEGES GRQRTESTAS VNSESWQNSD
EMMMNMRRAQ SLLDQGASCF QIIQQVFPEF DASRFENMSE RVHFKVLSDL LERAPTRQKL
FTYNSLSDAV DLFRTRKNIL VLTGAGVSVS CGIPDFRSKD GIYARLRSEF PNLPDPTAMF
DIRYFRDNPA PFYNFAREIF PGQFTPSVSH RFIKQLESSG RLLRNYTQNI DTLEHQTGIK
RVVECHGSFS KCTCTSCGNQ TDGMEIREDV LAMKVARCKI CHGVIKPNIV FFGEDLGREF
HRHVTEDKDK VDLIVVIGSS LKVRPVALIP HCVDKNVPQI LINRESLPHY NADIELLGNC
DDIVRDICYA LGGSFAEMIA SYDACVERSP STSRAKRQLI TQQEFLNICA QERRDKTPVP
EPESSEPSTK RPRMSTTEDM EGNQFQQIQK HTSSEDDDED NTRNSDEVLR EIKHPRLISI
TDMLNDKKCV AISAYQTVFP GAECSFDMET LKLVHDVPHR NRHESDSSCE SCSTVPGSDK
SEANPLSRSQ STDDIVYAEI RRKEVFLDLQ RCDSCDNDLQ YELSDPIDPE TFAKRIADMC
IE
