ID   RIR2_YEAST              Reviewed;         399 AA.
AC   P09938; D6VWF6;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 2.
DT   27-MAR-2024, entry version 230.
DE   RecName: Full=Ribonucleoside-diphosphate reductase small chain 1;
DE            EC=1.17.4.1;
DE   AltName: Full=Ribonucleotide reductase R2 subunit 1;
DE   AltName: Full=Ribonucleotide reductase small subunit 1;
GN   Name=RNR2; Synonyms=CRT6; OrderedLocusNames=YJL026W; ORFNames=J1271;
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], AND INDUCTION.
RX   PubMed=3313004; DOI=10.1128/mcb.7.8.2783-2793.1987;
RA   Elledge S.J., Davis R.W.;
RT   "Identification and isolation of the gene encoding the small subunit of
RT   ribonucleotide reductase from Saccharomyces cerevisiae: DNA damage-
RT   inducible gene required for mitotic viability.";
RL   Mol. Cell. Biol. 7:2783-2793(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RX   PubMed=3316984; DOI=10.1128/mcb.7.10.3673-3677.1987;
RA   Hurd H.K., Roberts C.W., Roberts J.W.;
RT   "Identification of the gene for the yeast ribonucleotide reductase small
RT   subunit and its inducibility by methyl methanesulfonate.";
RL   Mol. Cell. Biol. 7:3673-3677(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [4]
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   [5]
RP   FUNCTION, AND SUBUNIT.
RX   PubMed=10535923; DOI=10.1073/pnas.96.22.12339;
RA   Nguyen H.-H.T., Ge J., Perlstein D.L., Stubbe J.;
RT   "Purification of ribonucleotide reductase subunits Y1, Y2, Y3, and Y4 from
RT   yeast: Y4 plays a key role in diiron cluster assembly.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:12339-12344(1999).
RN   [6]
RP   SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=10716984; DOI=10.1073/pnas.97.6.2474;
RA   Chabes A., Domkin V., Larsson G., Liu A., Graeslund A., Wijmenga S.,
RA   Thelander L.;
RT   "Yeast ribonucleotide reductase has a heterodimeric iron-radical-containing
RT   subunit.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:2474-2479(2000).
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   SUBCELLULAR LOCATION.
RX   PubMed=12732713; DOI=10.1073/pnas.1131932100;
RA   Yao R., Zhang Z., An X., Bucci B., Perlstein D.L., Stubbe J., Huang M.;
RT   "Subcellular localization of yeast ribonucleotide reductase regulated by
RT   the DNA replication and damage checkpoint pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:6628-6633(2003).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=YAL6B;
RX   PubMed=15665377; DOI=10.1074/mcp.m400219-mcp200;
RA   Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M.,
RA   Jensen O.N.;
RT   "Quantitative phosphoproteomics applied to the yeast pheromone signaling
RT   pathway.";
RL   Mol. Cell. Proteomics 4:310-327(2005).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ADR376;
RX   PubMed=17330950; DOI=10.1021/pr060559j;
RA   Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA   Elias J.E., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of alpha-factor-arrested
RT   Saccharomyces cerevisiae.";
RL   J. Proteome Res. 6:1190-1197(2007).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA   Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA   Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT   "Analysis of phosphorylation sites on proteins from Saccharomyces
RT   cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN   [12]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH DIF1 AND RNR4.
RX   PubMed=18851834; DOI=10.1016/j.molcel.2008.08.018;
RA   Lee Y.D., Wang J., Stubbe J., Elledge S.J.;
RT   "Dif1 is a DNA-damage-regulated facilitator of nuclear import for
RT   ribonucleotide reductase.";
RL   Mol. Cell 32:70-80(2008).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15 AND SER-24, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX   PubMed=11526233; DOI=10.1073/pnas.181336398;
RA   Voegtli W.C., Ge J., Perlstein D.L., Stubbe J., Rosenzweig A.C.;
RT   "Structure of the yeast ribonucleotide reductase Y2Y4 heterodimer.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:10073-10078(2001).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
RX   PubMed=15196016; DOI=10.1021/bi049510m;
RA   Sommerhalter M., Voegtli W.C., Perlstein D.L., Ge J., Stubbe J.,
RA   Rosenzweig A.C.;
RT   "Structures of the yeast ribonucleotide reductase Rnr2 and Rnr4
RT   homodimers.";
RL   Biochemistry 43:7736-7742(2004).
CC   -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC       Catalyzes the biosynthesis of deoxyribonucleotides from the
CC       corresponding ribonucleotides. RNR2 provides the diiron-tyrosyl radical
CC       center. {ECO:0000269|PubMed:10535923}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-
CC         diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-
CC         diphosphate; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC         COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10014};
CC   -!- COFACTOR:
CC       Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC       Note=Binds 2 iron ions per subunit.;
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         Vmax=2250 nmol/min/mg enzyme for cytidine 5'-diphosphate
CC         {ECO:0000269|PubMed:10716984};
CC       Temperature dependence:
CC         Optimum temperature is 30 degrees Celsius.
CC         {ECO:0000269|PubMed:10716984};
CC   -!- SUBUNIT: Heterotetramer of two large (R1) and two small (R2) subunits.
CC       S.cerevisiae has two different R1 subunits (RNR1 and RNR3) and two
CC       different R2 subunits (RNR2 and RNR4). The functional form of the small
CC       subunits is a RNR2-RNR4 heterodimer, where RNR2 provides the iron-
CC       radical center and RNR4 is required for proper folding of RNR2 and
CC       assembly with the large subunits. Under normal growth conditions, the
CC       active form of the large subunits is a homodimer of the constitutively
CC       expressed RNR1. In damaged cells or cells arrested for DNA synthesis,
CC       the reductase consists of multiple species because of the association
CC       of the small subunits (RNR2-RNR4) with either the RNR1 homodimer or a
CC       heterodimer of RNR1 and the damage-inducible RNR3. Interacts with DIF1.
CC       {ECO:0000269|PubMed:10535923, ECO:0000269|PubMed:10716984,
CC       ECO:0000269|PubMed:18851834}.
CC   -!- INTERACTION:
CC       P09938; P21524: RNR1; NbExp=5; IntAct=EBI-15240, EBI-15234;
CC       P09938; P49723: RNR4; NbExp=8; IntAct=EBI-15240, EBI-15251;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12732713,
CC       ECO:0000269|PubMed:18851834}. Note=Found predominantly in the nucleus
CC       under normal growth conditions and is redistributed to the cytoplasm in
CC       damaged cells in a DNA replication and damage checkpoint-dependent
CC       manner. Nuclear localization is mediated by DIF1.
CC   -!- INDUCTION: Induced by DNA-damage. {ECO:0000269|PubMed:3313004,
CC       ECO:0000269|PubMed:3316984}.
CC   -!- MISCELLANEOUS: Present with 538 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small
CC       chain family. {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; M17221; AAA34987.1; -; Genomic_DNA.
DR   EMBL; M17789; AAA34988.1; -; Genomic_DNA.
DR   EMBL; Z49301; CAA89317.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08772.1; -; Genomic_DNA.
DR   PIR; A26916; A26916.
DR   RefSeq; NP_012508.1; NM_001181460.1.
DR   PDB; 1JK0; X-ray; 2.80 A; A=1-399.
DR   PDB; 1SMQ; X-ray; 3.10 A; A/B/C/D=1-399.
DR   PDB; 2CVY; X-ray; 2.40 A; B=391-399.
DR   PDBsum; 1JK0; -.
DR   PDBsum; 1SMQ; -.
DR   PDBsum; 2CVY; -.
DR   AlphaFoldDB; P09938; -.
DR   SMR; P09938; -.
DR   BioGRID; 33733; 84.
DR   ComplexPortal; CPX-1102; Ribonucleoside-diphosphate reductase variant 1.
DR   ComplexPortal; CPX-1103; Ribonucleoside-diphosphate reductase variant 2.
DR   DIP; DIP-5671N; -.
DR   IntAct; P09938; 28.
DR   MINT; P09938; -.
DR   STRING; 4932.YJL026W; -.
DR   iPTMnet; P09938; -.
DR   MaxQB; P09938; -.
DR   PaxDb; 4932-YJL026W; -.
DR   PeptideAtlas; P09938; -.
DR   TopDownProteomics; P09938; -.
DR   EnsemblFungi; YJL026W_mRNA; YJL026W; YJL026W.
DR   GeneID; 853427; -.
DR   KEGG; sce:YJL026W; -.
DR   AGR; SGD:S000003563; -.
DR   SGD; S000003563; RNR2.
DR   VEuPathDB; FungiDB:YJL026W; -.
DR   eggNOG; KOG1567; Eukaryota.
DR   GeneTree; ENSGT00390000013305; -.
DR   HOGENOM; CLU_035339_2_1_1; -.
DR   InParanoid; P09938; -.
DR   OMA; KVGEYQR; -.
DR   OrthoDB; 5487627at2759; -.
DR   BioCyc; MetaCyc:YJL026W-MONOMER; -.
DR   BioCyc; YEAST:YJL026W-MONOMER; -.
DR   BioGRID-ORCS; 853427; 4 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P09938; -.
DR   PRO; PR:P09938; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P09938; Protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR   GO; GO:0005634; C:nucleus; IDA:SGD.
DR   GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IDA:SGD.
DR   GO; GO:0008198; F:ferrous iron binding; IDA:CAFA.
DR   GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt.
DR   GO; GO:0046982; F:protein heterodimerization activity; IDA:CAFA.
DR   GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IDA:SGD.
DR   GO; GO:0008270; F:zinc ion binding; IDA:CAFA.
DR   GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IDA:SGD.
DR   CDD; cd01049; RNRR2; 1.
DR   DisProt; DP00487; -.
DR   Gene3D; 1.10.620.20; Ribonucleotide Reductase, subunit A; 1.
DR   InterPro; IPR009078; Ferritin-like_SF.
DR   InterPro; IPR012348; RNR-like.
DR   InterPro; IPR033909; RNR_small.
DR   InterPro; IPR030475; RNR_small_AS.
DR   InterPro; IPR000358; RNR_small_fam.
DR   PANTHER; PTHR23409; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE SMALL CHAIN; 1.
DR   PANTHER; PTHR23409:SF18; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE SUBUNIT M2; 1.
DR   Pfam; PF00268; Ribonuc_red_sm; 1.
DR   SUPFAM; SSF47240; Ferritin-like; 1.
DR   PROSITE; PS00368; RIBORED_SMALL; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Deoxyribonucleotide synthesis; Iron; Metal-binding; Nucleus;
KW   Oxidoreductase; Phosphoprotein; Reference proteome.
FT   CHAIN           1..399
FT                   /note="Ribonucleoside-diphosphate reductase small chain 1"
FT                   /id="PRO_0000190464"
FT   ACT_SITE        183
FT   BINDING         145
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="1"
FT   BINDING         176
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="1"
FT   BINDING         176
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   BINDING         179
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="1"
FT   BINDING         239
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   BINDING         273
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   BINDING         276
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   MOD_RES         15
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:15665377,
FT                   ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
FT   MOD_RES         24
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         41
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17287358"
FT   CONFLICT        101..103
FT                   /note="Missing (in Ref. 1; AAA34987)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        111
FT                   /note="E -> ETAE (in Ref. 1)"
FT                   /evidence="ECO:0000305"
FT   HELIX           27..36
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           38..49
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           51..61
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           63..72
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           73..75
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           77..79
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           94..104
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           110..112
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           118..124
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           128..142
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           147..152
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           153..157
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           163..190
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           194..204
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           208..220
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   STRAND          223..225
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           228..240
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   TURN            241..243
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           244..255
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           260..285
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           293..312
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           317..320
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           324..340
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   TURN            341..343
FT                   /evidence="ECO:0007829|PDB:1JK0"
FT   HELIX           355..358
FT                   /evidence="ECO:0007829|PDB:1JK0"
SQ   SEQUENCE   399 AA;  46147 MW;  DB98028408292042 CRC64;
     MPKETPSKAA ADALSDLEIK DSKSNLNKEL ETLREENRVK SDMLKEKLSK DAENHKAYLK
     SHQVHRHKLK EMEKEEPLLN EDKERTVLFP IKYHEIWQAY KRAEASFWTA EEIDLSKDIH
     DWNNRMNENE RFFISRVLAF FAASDGIVNE NLVENFSTEV QIPEAKSFYG FQIMIENIHS
     ETYSLLIDTY IKDPKESEFL FNAIHTIPEI GEKAEWALRW IQDADALFGE RLVAFASIEG
     VFFSGSFASI FWLKKRGMMP GLTFSNELIC RDEGLHTDFA CLLFAHLKNK PDPAIVEKIV
     TEAVEIEQRY FLDALPVALL GMNADLMNQY VEFVADRLLV AFGNKKYYKV ENPFDFMENI
     SLAGKTNFFE KRVSDYQKAG VMSKSTKQEA GAFTFNEDF
//