SML1_YEAST
ID SML1_YEAST Reviewed; 104 AA.
AC Q04964; D6VZB6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Ribonucleotide reductase inhibitor protein SML1;
GN Name=SML1; OrderedLocusNames=YML058W; ORFNames=YM9958.04;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(1997).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP PROTEIN SEQUENCE OF 1-7, AND INTERCHAIN DISULFIDE BOND.
RX PubMed=15222768; DOI=10.1021/bi0361721;
RA Gupta V., Peterson C.B., Dice L.T., Uchiki T., Racca J., Guo J.T., Xu Y.,
RA Hettich R., Zhao X., Rothstein R., Dealwis C.G.;
RT "Sml1p is a dimer in solution: characterization of denaturation and
RT renaturation of recombinant Sml1p.";
RL Biochemistry 43:8568-8578(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH RNR1.
RX PubMed=10593972; DOI=10.1074/jbc.274.51.36679;
RA Chabes A., Domkin V., Thelander L.;
RT "Yeast Sml1, a protein inhibitor of ribonucleotide reductase.";
RL J. Biol. Chem. 274:36679-36683(1999).
RN [6]
RP REGULATION BY DUN1.
RX PubMed=11904430; DOI=10.1073/pnas.062502299;
RA Zhao X., Rothstein R.;
RT "The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide
RT reductase inhibitor Sml1.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:3746-3751(2002).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP PHOSPHORYLATION AT SER-56; SER-58 AND SER-60.
RX PubMed=14684746; DOI=10.1074/jbc.m309751200;
RA Uchiki T., Dice L.T., Hettich R.L., Dealwis C.;
RT "Identification of phosphorylation sites on the yeast ribonucleotide
RT reductase inhibitor Sml1.";
RL J. Biol. Chem. 279:11293-11303(2004).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PHOSPHORYLATION,
RP UBIQUITINATION, AND MUTAGENESIS OF 56-SER--SER-61.
RX PubMed=20566477; DOI=10.1093/nar/gkq552;
RA Andreson B.L., Gupta A., Georgieva B.P., Rothstein R.;
RT "The ribonucleotide reductase inhibitor, Sml1, is sequentially
RT phosphorylated, ubiquitylated and degraded in response to DNA damage.";
RL Nucleic Acids Res. 38:6490-6501(2010).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Strong inhibitor of ribonucleotide reductase (RNR1) and is
CC involved in regulating dNTP production. {ECO:0000269|PubMed:10593972,
CC ECO:0000269|PubMed:20566477}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with RNR1.
CC {ECO:0000269|PubMed:10593972}.
CC -!- INTERACTION:
CC Q04964; P21524: RNR1; NbExp=4; IntAct=EBI-27834, EBI-15234;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20566477}. Cytoplasm
CC {ECO:0000269|PubMed:20566477}.
CC -!- DEVELOPMENTAL STAGE: Levels decrease during S phase.
CC {ECO:0000269|PubMed:20566477}.
CC -!- PTM: Phosphorylated by DUN1, a downstream effector of the Mec1/Rad53
CC checkpoint pathway, in response to DNA damage. This promotes
CC ubiquitination of SML1 and targets it for degradation by the 26S
CC proteasome. {ECO:0000269|PubMed:14684746, ECO:0000269|PubMed:20566477}.
CC -!- MISCELLANEOUS: Present with 18800 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
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DR EMBL; Z46729; CAA86717.1; -; Genomic_DNA.
DR EMBL; AY557961; AAS56287.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA09840.1; -; Genomic_DNA.
DR PIR; S49803; S49803.
DR RefSeq; NP_013653.1; NM_001182417.1.
DR AlphaFoldDB; Q04964; -.
DR BMRB; Q04964; -.
DR BioGRID; 35109; 156.
DR DIP; DIP-2734N; -.
DR IntAct; Q04964; 24.
DR MINT; Q04964; -.
DR STRING; 4932.YML058W; -.
DR iPTMnet; Q04964; -.
DR MaxQB; Q04964; -.
DR PaxDb; Q04964; -.
DR PRIDE; Q04964; -.
DR EnsemblFungi; YML058W_mRNA; YML058W; YML058W.
DR GeneID; 854945; -.
DR KEGG; sce:YML058W; -.
DR SGD; S000004523; SML1.
DR VEuPathDB; FungiDB:YML058W; -.
DR eggNOG; ENOG502S8G2; Eukaryota.
DR HOGENOM; CLU_171972_0_0_1; -.
DR InParanoid; Q04964; -.
DR OMA; MLEKNCT; -.
DR BioCyc; YEAST:G3O-32653-MON; -.
DR PRO; PR:Q04964; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; Q04964; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:1990846; F:ribonucleoside-diphosphate reductase inhibitor activity; IDA:SGD.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:SGD.
DR GO; GO:0007005; P:mitochondrion organization; IMP:SGD.
DR GO; GO:0008156; P:negative regulation of DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0008104; P:protein localization; IBA:GO_Central.
DR GO; GO:1905117; P:regulation of ribonucleoside-diphosphate reductase activity; IDA:SGD.
DR DisProt; DP01559; -.
PE 1: Evidence at protein level;
KW Acetylation; Cell cycle; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; DNA damage; DNA replication inhibitor; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..104
FT /note="Ribonucleotide reductase inhibitor protein SML1"
FT /id="PRO_0000071974"
FT REGION 43..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 56
FT /note="Phosphoserine; by DUN1"
FT /evidence="ECO:0000269|PubMed:14684746"
FT MOD_RES 58
FT /note="Phosphoserine; by DUN1"
FT /evidence="ECO:0000269|PubMed:14684746"
FT MOD_RES 60
FT /note="Phosphoserine; by DUN1"
FT /evidence="ECO:0000269|PubMed:14684746"
FT DISULFID 14
FT /note="Interchain"
FT MUTAGEN 56..61
FT /note="SASASS->AAAAAA: Increased stability following gamma-
FT irradiation and loss of phosphorylation by DUN1. Causes
FT lethality in rnr1-W688G strain which has a mutation in
FT RNR1."
FT /evidence="ECO:0000269|PubMed:20566477"
SQ SEQUENCE 104 AA; 11834 MW; 02735C9178E431B2 CRC64;
MQNSQDYFYA QNRCQQQQAP STLRTVTMAE FRRVPLPPMA EVPMLSTQNS MGSSASASAS
SLEMWEKDLE ERLNSIDHDM NNNKFGSGEL KSMFNQGKVE EMDF
