SIR1_YEAST
ID SIR1_YEAST Reviewed; 654 AA.
AC P21691; D6VXG2;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Regulatory protein SIR1;
DE AltName: Full=Heterochromatin protein SIR1;
DE AltName: Full=Silent information regulator 1;
GN Name=SIR1; OrderedLocusNames=YKR101W;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2005909; DOI=10.1128/mcb.11.4.2253-2262.1991;
RA Stone E.M., Swanson M.J., Romeo A.M., Hicks J.B., Sternglanz R.;
RT "The SIR1 gene of Saccharomyces cerevisiae and its role as an extragenic
RT suppressor of several mating-defective mutants.";
RL Mol. Cell. Biol. 11:2253-2262(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=8221892; DOI=10.1016/0092-8674(93)90387-6;
RA Chien C.T., Buck S., Sternglanz R., Shore D.;
RT "Targeting of SIR1 protein establishes transcriptional silencing at HM loci
RT and telomeres in yeast.";
RL Cell 75:531-541(1993).
RN [5]
RP FUNCTION, AND INTERACTION WITH ORC1.
RX PubMed=8622770; DOI=10.1038/381251a0;
RA Triolo T., Sternglanz R.;
RT "Role of interactions between the origin recognition complex and SIR1 in
RT transcriptional silencing.";
RL Nature 381:251-253(1996).
RN [6]
RP REVIEW.
RX PubMed=11722841; DOI=10.1016/s0378-1119(01)00741-7;
RA Gasser S.M., Cockell M.M.;
RT "The molecular biology of the SIR proteins.";
RL Gene 279:1-16(2001).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=11157772; DOI=10.1101/gad.852801;
RA Gardner K.A., Fox C.A.;
RT "The Sir1 protein's association with a silenced chromosome domain.";
RL Genes Dev. 15:147-157(2001).
RN [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ORC1.
RX PubMed=12198162; DOI=10.1093/emboj/cdf468;
RA Zhang Z., Hayashi M.K., Merkel O., Stillman B., Xu R.-M.;
RT "Structure and function of the BAH-containing domain of Orc1p in epigenetic
RT silencing.";
RL EMBO J. 21:4600-4611(2002).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12134062; DOI=10.1091/mbc.e02-03-0175;
RA Rusche L.N., Kirchmaier A.L., Rine J.;
RT "Ordered nucleation and spreading of silenced chromatin in Saccharomyces
RT cerevisiae.";
RL Mol. Biol. Cell 13:2207-2222(2002).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CAC1.
RX PubMed=12975325; DOI=10.1101/gad.1131103;
RA Sharp J.A., Krawitz D.C., Gardner K.A., Fox C.A., Kaufman P.D.;
RT "The budding yeast silencing protein Sir1 is a functional component of
RT centromeric chromatin.";
RL Genes Dev. 17:2356-2361(2003).
RN [11]
RP INTERACTION WITH ORC1 AND SIR4, AND MUTAGENESIS OF 462-GLU--GLU-464;
RP VAL-466; ARG-469; PHE-470; LEU-477; ASP-479; LEU-480; 482-GLU-GLU-483;
RP 489-LYS-ASP-490; 498-LYS-ASP-499; TRP-513; 517-LYS-LYS-518; CYS-534;
RP 538-LYS--LYS-540; CYS-571; VAL-572; PRO-573; 577-ASP-ASP-578; LEU-584 AND
RP 586-ASP-ASP-587.
RX PubMed=14701749; DOI=10.1128/mcb.24.2.774-786.2004;
RA Bose M.E., McConnell K.H., Gardner-Aukema K.A., Mueller U., Weinreich M.,
RA Keck J.L., Fox C.A.;
RT "The origin recognition complex and Sir4 protein recruit Sir1p to yeast
RT silent chromatin through independent interactions requiring a common Sir1p
RT domain.";
RL Mol. Cell. Biol. 24:774-786(2004).
RN [12]
RP IDENTIFICATION OF INITIATION SITE.
RX PubMed=19171939; DOI=10.1534/genetics.108.099663;
RA Gallagher J.E.G., Babiarz J.E., Teytelman L., Wolfe K.H., Rine J.;
RT "Elaboration, diversification and regulation of the sir1 family of
RT silencing proteins in Saccharomyces.";
RL Genetics 181:1477-1491(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 449-587 OF MUTANT ALA-569 IN
RP COMPLEX WITH ORC1.
RX PubMed=15932939; DOI=10.1073/pnas.0503525102;
RA Hou Z., Bernstein D.A., Fox C.A., Keck J.L.;
RT "Structural basis of the Sir1-origin recognition complex interaction in
RT transcriptional silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8489-8494(2005).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 456-588 IN COMPLEX WITH ORC1.
RX PubMed=15937111; DOI=10.1073/pnas.0502946102;
RA Hsu H.-C., Stillman B., Xu R.-M.;
RT "Structural basis for origin recognition complex 1 protein-silence
RT information regulator 1 protein interaction in epigenetic silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8519-8524(2005).
CC -!- FUNCTION: Involved in the establishment, but not the maintenance, of
CC heterochromatic silencing at the cryptic mating-type loci HMR and HML.
CC Is recruited by interacting with the ORC1 subunit of the origin
CC recognition complex (ORC), which binds to HML-I or HMR-E silencers, DNA
CC elements that direct the formation of silent chromatin at the mating-
CC type loci. Establishes transcriptional silencing by recruiting the
CC three other SIR proteins, SIR2, SIR3, and SIR4, that function directly
CC in silenced chromatin and establish repression. Also found in
CC centromeric chromatin. Binds to and helps retain CAC1, a subunit of
CC chromatin assembly factor I (CAF-I) at centromeric loci independent on
CC the other SIR proteins. {ECO:0000269|PubMed:12134062,
CC ECO:0000269|PubMed:8221892, ECO:0000269|PubMed:8622770}.
CC -!- SUBUNIT: Interacts (via OIR domain) with ORC1 (via BAH domain).
CC Interacts with SIR4. Interacts with CAC1. {ECO:0000269|PubMed:12198162,
CC ECO:0000269|PubMed:12975325, ECO:0000269|PubMed:14701749,
CC ECO:0000269|PubMed:15932939, ECO:0000269|PubMed:15937111,
CC ECO:0000269|PubMed:8622770}.
CC -!- INTERACTION:
CC P21691; P54784: ORC1; NbExp=3; IntAct=EBI-17211, EBI-12568;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere. Note=Associated
CC primarily with the HMR-E silencer at the HMR locus.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35046.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA82181.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M38524; AAA35046.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z28326; CAA82181.1; ALT_INIT; Genomic_DNA.
DR EMBL; BK006944; DAA09252.1; -; Genomic_DNA.
DR PIR; S14173; S14173.
DR RefSeq; NP_013027.4; NM_001179891.3.
DR PDB; 1Z1A; X-ray; 2.50 A; A/B=449-587.
DR PDB; 1ZBX; X-ray; 2.50 A; B=456-588.
DR PDB; 1ZHI; X-ray; 2.70 A; B=456-587.
DR PDBsum; 1Z1A; -.
DR PDBsum; 1ZBX; -.
DR PDBsum; 1ZHI; -.
DR AlphaFoldDB; P21691; -.
DR SMR; P21691; -.
DR BioGRID; 34232; 83.
DR DIP; DIP-2453N; -.
DR IntAct; P21691; 6.
DR MINT; P21691; -.
DR STRING; 4932.YKR101W; -.
DR MaxQB; P21691; -.
DR PaxDb; P21691; -.
DR PRIDE; P21691; -.
DR EnsemblFungi; YKR101W_mRNA; YKR101W; YKR101W.
DR GeneID; 853976; -.
DR KEGG; sce:YKR101W; -.
DR SGD; S000001809; SIR1.
DR VEuPathDB; FungiDB:YKR101W; -.
DR eggNOG; ENOG502SG8F; Eukaryota.
DR HOGENOM; CLU_449838_0_0_1; -.
DR InParanoid; P21691; -.
DR OMA; IFDECHE; -.
DR BioCyc; YEAST:G3O-32063-MON; -.
DR EvolutionaryTrace; P21691; -.
DR PRO; PR:P21691; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P21691; protein.
DR GO; GO:0005677; C:chromatin silencing complex; IDA:SGD.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IDA:SGD.
DR GO; GO:0031507; P:heterochromatin assembly; IMP:SGD.
DR GO; GO:0030466; P:silent mating-type cassette heterochromatin assembly; IDA:SGD.
DR InterPro; IPR037240; ORC1-binding_dom.
DR InterPro; IPR021646; Sir1_ORC-binding.
DR Pfam; PF11603; Sir1; 2.
DR SUPFAM; SSF144005; SSF144005; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Centromere; Chromosome; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..654
FT /note="Regulatory protein SIR1"
FT /id="PRO_0000097767"
FT REGION 322..654
FT /note="Sufficient for interaction with SIR4"
FT /evidence="ECO:0000269|PubMed:14701749"
FT REGION 449..587
FT /note="ORC interacting region (OIR)"
FT MUTAGEN 462..464
FT /note="EEE->AAA: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 466
FT /note="V->G: Abolishes interaction with ORC1."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 469
FT /note="R->G: Abolishes interaction with ORC1."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 470
FT /note="F->S: Abolishes interaction with ORC1 and SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 477
FT /note="L->P: Abolishes interaction with ORC1 and SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 479
FT /note="D->N: Abolishes interaction with ORC1."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 480
FT /note="L->P: Abolishes interaction with ORC1."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 482..483
FT /note="EE->AA: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 489..490
FT /note="KD->AA: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 498..499
FT /note="KD->AA: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 513
FT /note="W->R: Abolishes interaction with ORC1 and SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 517..518
FT /note="KK->AA: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 534
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 538..540
FT /note="KKK->AAA: Abolishes interaction with SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 569
FT /note="C->A: No effect."
FT MUTAGEN 571
FT /note="C->R: Abolishes interaction with ORC1 and SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 572
FT /note="V->G: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 573
FT /note="P->S: No effect."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 577..578
FT /note="DD->AA: Abolishes interaction with SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 584
FT /note="L->P,Q: Abolishes interaction with ORC1 and SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT MUTAGEN 586..587
FT /note="DD->AA: Abolishes interaction with SIR4."
FT /evidence="ECO:0000269|PubMed:14701749"
FT STRAND 464..473
FT /evidence="ECO:0007829|PDB:1Z1A"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:1Z1A"
FT TURN 480..483
FT /evidence="ECO:0007829|PDB:1Z1A"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:1Z1A"
FT HELIX 493..496
FT /evidence="ECO:0007829|PDB:1Z1A"
FT HELIX 499..506
FT /evidence="ECO:0007829|PDB:1Z1A"
FT HELIX 513..516
FT /evidence="ECO:0007829|PDB:1Z1A"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:1Z1A"
FT HELIX 530..533
FT /evidence="ECO:0007829|PDB:1Z1A"
FT STRAND 537..543
FT /evidence="ECO:0007829|PDB:1Z1A"
FT STRAND 547..550
FT /evidence="ECO:0007829|PDB:1Z1A"
FT STRAND 566..575
FT /evidence="ECO:0007829|PDB:1Z1A"
FT STRAND 577..579
FT /evidence="ECO:0007829|PDB:1ZBX"
FT STRAND 581..586
FT /evidence="ECO:0007829|PDB:1Z1A"
SQ SEQUENCE 654 AA; 76933 MW; 00FEABD1BD35BC81 CRC64;
MLQINSRLAV IDGWLVDTVK RKPINFRSPE VRLLLPNDDD YKKLSQQNLV DWTRLKKDSN
SVLVGVKSME LFKHIKLVLR EFFLLEDGRI ILKRIRSKLR YKVVKKLTCK CCRLYLPKWG
TVYIHPMLKD KEKPLAGVCE FSLDVNPDRE YPLIEINVSH QYIIIEGFLL YLNERRLYRW
NDNNLRSQVG LTKWAHLRKT YNPVSLDILY SLNSNFYFVK DDLLFQLLGK RVFVKFCKVM
ENGKCGKAPL WYRVKRTTTA KATHIAYAIS NSTAPDSFKS KNNDYRFIVR EKPIVENTIS
NLDYSDIKKQ QFTEAEVVKR KISADISQIE NVHTQFNSQK EKNNIRVNKV SSEVLDQISK
FPVSRVTLLL MSAGQDKNYI ELVEELARRL EKICIEKTTQ SLEEIRDTFQ ANPEMQASFD
KEYYQSIEEY KITLELIKED LLITLIKQME NMWAAEKKFS TEEEYVSPRF LVADGFLIDL
AEEKPINPKD PRLLTLLKDH QRAMIDQMNL VKWNDFKKYQ DPIPLKAKTL FKFCKQIKKK
FLRGADFKLH TLPTEANLKY EPERMTVLCS CVPILLDDQT VQYLYDDSII PEFEATSSYA
TKQSKCGRKM SLQMEPDLLF QEAIRRMRHL TAYDVLRRNY IAAFEELYMG NCND
