SIR2_CANAL
ID SIR2_CANAL Reviewed; 519 AA.
AC O59923; A0A1D8PGB6; Q5AD75; Q5ADK3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=NAD-dependent histone deacetylase SIR2 {ECO:0000305};
DE EC=2.3.1.286 {ECO:0000250|UniProtKB:P06700};
DE AltName: Full=Regulatory protein SIR2 {ECO:0000305};
DE AltName: Full=Silent information regulator 2 {ECO:0000305};
GN Name=SIR2 {ECO:0000303|PubMed:10228170}; Synonyms=SIR21;
GN OrderedLocusNames=CAALFM_C201330CA; ORFNames=CaO19.1992, CaO19.9544;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, AND FUNCTION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=10228170; DOI=10.1093/emboj/18.9.2580;
RA Perez-Martin J., Uria J.A., Johnson A.D.;
RT "Phenotypic switching in Candida albicans is controlled by a SIR2 gene.";
RL EMBO J. 18:2580-2592(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18691183; DOI=10.1111/j.1474-9726.2008.00424.x;
RA Fu X.H., Meng F.L., Hu Y., Zhou J.Q.;
RT "Candida albicans, a distinctive fungal model for cellular aging study.";
RL Aging Cell 7:746-757(2008).
RN [6]
RP INDUCTION.
RX PubMed=19120662; DOI=10.1111/j.1365-2672.2008.03912.x;
RA Low C.F., Chong P.P., Yong P.V., Lim C.S., Ahmad Z., Othman F.;
RT "Inhibition of hyphae formation and SIR2 expression in Candida albicans
RT treated with fresh Allium sativum (garlic) extract.";
RL J. Appl. Microbiol. 105:2169-2177(2008).
RN [7]
RP INDUCTION.
RX PubMed=19810039; DOI=10.1002/jobm.200900035;
RA Lim C.S., Wong W.F., Rosli R., Ng K.P., Seow H.F., Chong P.P.;
RT "2-dodecanol (decyl methyl carbinol) inhibits hyphal formation and SIR2
RT expression in C. albicans.";
RL J. Basic Microbiol. 49:579-583(2009).
RN [8]
RP INDUCTION.
RX PubMed=22433888;
RA Khodavandi A., Alizadeh F., Harmal N.S., Sidik S.M., Othman F., Sekawi Z.,
RA Chong P.P.;
RT "Expression analysis of SIR2 and SAPs1-4 gene expression in Candida
RT albicans treated with allicin compared to fluconazole.";
RL Trop. Biomed. 28:589-598(2011).
RN [9]
RP INTERACTION WITH HXK1, AND FUNCTION.
RX PubMed=23341961; DOI=10.1371/journal.pone.0053638;
RA Rao K.H., Ghosh S., Natarajan K., Datta A.;
RT "N-acetylglucosamine kinase, HXK1 is involved in morphogenetic transition
RT and metabolic gene expression in Candida albicans.";
RL PLoS ONE 8:E53638-E53638(2013).
CC -!- FUNCTION: NAD-dependent deacetylase. Heterochromatin component that
CC silences transcription at silent mating loci, telomeres and the
CC ribosomal DNA, and that also suppresses recombination in the rDNA and
CC extends replicative life span. It acts as a NAD-dependent histone
CC deacetylase, which deacetylates 'Lys-9' and 'Lys-14' of Histone H3 and
CC 'Lys-16' of Histone H4. Functions in the distribution of oxidatively
CC damaged proteins during cell division. Mediates phenotypic switching.
CC {ECO:0000269|PubMed:10228170, ECO:0000269|PubMed:18691183,
CC ECO:0000269|PubMed:23341961}.
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 HXK1. {ECO:0000269|PubMed:23341961}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250,
CC ECO:0000250|UniProtKB:P06700}.
CC -!- INDUCTION: Expression is up-regulated and increases progressively with
CC hyphal development. Expression is inhibited by 2-dodecanol and
CC decreased by allicin and fluconazole. {ECO:0000269|PubMed:19120662,
CC ECO:0000269|PubMed:19810039, ECO:0000269|PubMed:22433888}.
CC -!- DISRUPTION PHENOTYPE: Leads to high frequency phenotypic switching,
CC spontaneous hyphal growth, and decreased replicative lifespan. Shows
CC also oxidatively damaged proteins even distribution between mother and
CC daughter cells during division. {ECO:0000269|PubMed:10228170,
CC ECO:0000269|PubMed:18691183}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; AF045774; AAC09304.1; -; Genomic_DNA.
DR EMBL; CP017624; AOW27179.1; -; Genomic_DNA.
DR RefSeq; XP_719442.1; XM_714349.1.
DR AlphaFoldDB; O59923; -.
DR SMR; O59923; -.
DR STRING; 237561.O59923; -.
DR PRIDE; O59923; -.
DR GeneID; 3638845; -.
DR KEGG; cal:CAALFM_C201330CA; -.
DR CGD; CAL0000181323; SIR2.
DR VEuPathDB; FungiDB:C2_01330C_A; -.
DR eggNOG; KOG2684; Eukaryota.
DR HOGENOM; CLU_023643_5_0_1; -.
DR InParanoid; O59923; -.
DR OMA; PDFRSFK; -.
DR OrthoDB; 973532at2759; -.
DR PRO; PR:O59923; -.
DR Proteomes; UP000000559; Chromosome 2.
DR GO; GO:0005634; C:nucleus; IDA:CGD.
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:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 specific); IBA:GO_Central.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0048239; P:negative regulation of DNA recombination at telomere; IMP:CGD.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; IMP:CGD.
DR GO; GO:0045595; P:regulation of cell differentiation; IMP:CGD.
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 Metal-binding; NAD; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT CHAIN 1..519
FT /note="NAD-dependent histone deacetylase SIR2"
FT /id="PRO_0000110275"
FT DOMAIN 229..488
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 154..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..168
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..208
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 348
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 246..265
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 328..331
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 356
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 359
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 380
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 430..432
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 455..457
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 472
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT CONFLICT 96
FT /note="L -> P (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="V -> A (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 173..176
FT /note="Missing (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="D -> G (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="S -> P (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 289..290
FT /note="PG -> GR (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="V -> A (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="F -> L (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
FT CONFLICT 512
FT /note="K -> N (in Ref. 1; AAC09304)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 58272 MW; 5E36759F6B3C175B CRC64;
MTTFWSQTIN RQNGGVATAT ATATATAATT TPTAGGTGAG TTTSTKGMIT PTPFNIDINN
DLNDFDGKFI ETFKPDLELQ KKYRSFIQRE GALSFLRTEI TQSMSKRDIC VLILNLGYPK
KAVEDYPILT LKELAYILLK LMLTDSAQLE PKVEIDENDN KNDGTNNSDI DSDIDSNSDM
DSQSESGELD DAMDVDDSLS ENEDEYDQDM STTTLKRTIN MTPFKYKLPD LISDLSRAKK
IMVVTGAGIS TSLGIPDFRS FKGLYNQLSK LNLSDPQKVF DLQTFMREPG LFYTIAHLVL
PPDGKFSLLH AFLKLLQDKH KLLRNYTQNI DNLEQRAGLK SEKLVQCHGS FAKAKCVSCQ
GIFAGEKIYN HIRRKQVPRC AICWKNTKQA PIHFGAIKPT ITFFGEDLPE RFHTLMDKDL
QQIDLFLVIG TSLKVEPVAS IIERVPYKVP KILINKDPIP NRGFNLQLLG LCDDVVSYLC
KCLKWDIPHA DFNNNDEFKL SKLKNGDWEI VKKSTSTKK
