RIR2_YEAST
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 03-AUG-2022, entry version 221.
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 -!- PATHWAY: Genetic information processing; DNA replication.
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}.
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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; 75.
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; P09938; -.
DR PRIDE; P09938; -.
DR TopDownProteomics; P09938; -.
DR EnsemblFungi; YJL026W_mRNA; YJL026W; YJL026W.
DR GeneID; 853427; -.
DR KEGG; sce:YJL026W; -.
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 BioCyc; MetaCyc:YJL026W-MON; -.
DR BioCyc; YEAST:YJL026W-MON; -.
DR UniPathway; UPA00326; -.
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: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 GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR CDD; cd01049; RNRR2; 1.
DR DisProt; DP00487; -.
DR Gene3D; 1.10.620.20; -; 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; PTHR23409; 1.
DR Pfam; PF00268; Ribonuc_red_sm; 1.
DR SUPFAM; SSF47240; SSF47240; 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
