RIR2_MOUSE
ID RIR2_MOUSE Reviewed; 390 AA.
AC P11157; Q3UI23; Q542E2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Ribonucleoside-diphosphate reductase subunit M2;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase small chain;
DE AltName: Full=Ribonucleotide reductase small subunit;
GN Name=Rrm2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3025593; DOI=10.1128/mcb.6.10.3433-3442.1986;
RA Thelander L., Berg P.;
RT "Isolation and characterization of expressible cDNA clones encoding the M1
RT and M2 subunits of mouse ribonucleotide reductase.";
RL Mol. Cell. Biol. 6:3433-3442(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2684652; DOI=10.1002/j.1460-2075.1989.tb08383.x;
RA Thelander M., Thelander L.;
RT "Molecular cloning and expression of the functional gene encoding the M2
RT subunit of mouse ribonucleotide reductase: a new dominant marker gene.";
RL EMBO J. 8:2475-2479(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, DBA/2J, and NOD; TISSUE=Eye, Kidney, Liver, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20 AND THR-33, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 65-352.
RX PubMed=8876648; DOI=10.1006/jmbi.1996.0546;
RA Kauppi B., Nielsen B.B., Ramaswamy S., Larsen I.K., Thelander M.,
RA Thelander L., Eklund H.;
RT "The three-dimensional structure of mammalian ribonucleotide reductase
RT protein R2 reveals a more-accessible iron-radical site than Escherichia
RT coli R2.";
RL J. Mol. Biol. 262:706-720(1996).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 65-352.
RX PubMed=12087093; DOI=10.1074/jbc.m203358200;
RA Strand K.R., Karlsen S., Andersson K.K.;
RT "Cobalt substitution of mouse R2 ribonucleotide reductase as a model for
RT the reactive diferrous state. Spectroscopic and structural evidence for a
RT ferromagnetically coupled dinuclear cobalt cluster.";
RL J. Biol. Chem. 277:34229-34238(2002).
RN [10]
RP STRUCTURE BY NMR OF 384-390.
RX PubMed=7583667; DOI=10.1038/nsb1195-951;
RA Fisher A.L., Laub P.B., Cooperman B.S.;
RT "NMR structure of an inhibitory R2 C-terminal peptide bound to mouse
RT ribonucleotide reductase R1 subunit.";
RL Nat. Struct. Biol. 2:951-955(1995).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides. Inhibits Wnt signaling (By similarity).
CC {ECO:0000250}.
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 -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Heterodimer of a large and a small subunit. Interacts (via Cy
CC motif and when phosphorylated at Thr-33) with CCNF; the interaction
CC occurs exclusively in G2 and early M (By similarity).
CC {ECO:0000250|UniProtKB:P31350}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P31350}. Nucleus
CC {ECO:0000250|UniProtKB:P31350}. Note=Localized to the cytoplasm in S
CC phase cells. May localize to the nucleus in G2 phase cells.
CC {ECO:0000250|UniProtKB:P31350}.
CC -!- PTM: Phosphorylation on Ser-20 relieves the inhibitory effect on Wnt
CC signaling (By similarity). Phosphorylated on Thr-33 by CDK1 and CDK2;
CC predominantly in G2 and M phase (By similarity).
CC {ECO:0000250|UniProtKB:P31350}.
CC -!- PTM: Ubiquitinated by the SCF(CCNF) E3 ubiquitin-protein ligase
CC complex; leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:P31350}.
CC -!- MISCELLANEOUS: Two distinct regulatory sites have been defined: the
CC specificity site, which controls substrate specificity, and the
CC activity site which regulates overall catalytic activity. A substrate-
CC binding catalytic site, located on M1, is formed only in the presence
CC of the second subunit M2.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small
CC chain family. {ECO:0000305}.
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DR EMBL; M14223; AAA40062.1; -; mRNA.
DR EMBL; X15666; CAA33707.1; -; Genomic_DNA.
DR EMBL; AK088907; BAC40647.1; -; mRNA.
DR EMBL; AK142027; BAE24918.1; -; mRNA.
DR EMBL; AK147111; BAE27683.1; -; mRNA.
DR EMBL; AK161643; BAE36508.1; -; mRNA.
DR EMBL; AK167078; BAE39238.1; -; mRNA.
DR EMBL; AK167204; BAE39331.1; -; mRNA.
DR EMBL; AK168205; BAE40165.1; -; mRNA.
DR EMBL; AK168994; BAE40793.1; -; mRNA.
DR EMBL; BC085136; AAH85136.1; -; mRNA.
DR CCDS; CCDS25844.1; -.
DR PIR; S06735; S06735.
DR RefSeq; NP_033130.1; NM_009104.2.
DR PDB; 1AFT; NMR; -; A=384-390.
DR PDB; 1H0N; X-ray; 2.40 A; A=1-390.
DR PDB; 1H0O; X-ray; 2.20 A; A=1-390.
DR PDB; 1W68; X-ray; 2.20 A; A=1-390.
DR PDB; 1W69; X-ray; 2.20 A; A=1-390.
DR PDB; 1XSM; X-ray; 2.30 A; A=1-390.
DR PDBsum; 1AFT; -.
DR PDBsum; 1H0N; -.
DR PDBsum; 1H0O; -.
DR PDBsum; 1W68; -.
DR PDBsum; 1W69; -.
DR PDBsum; 1XSM; -.
DR AlphaFoldDB; P11157; -.
DR SMR; P11157; -.
DR BioGRID; 203023; 4.
DR ComplexPortal; CPX-370; Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant.
DR IntAct; P11157; 1.
DR STRING; 10090.ENSMUSP00000020980; -.
DR ChEMBL; CHEMBL3527; -.
DR iPTMnet; P11157; -.
DR PhosphoSitePlus; P11157; -.
DR EPD; P11157; -.
DR jPOST; P11157; -.
DR MaxQB; P11157; -.
DR PaxDb; P11157; -.
DR PeptideAtlas; P11157; -.
DR PRIDE; P11157; -.
DR ProteomicsDB; 254887; -.
DR Antibodypedia; 26663; 318 antibodies from 36 providers.
DR DNASU; 20135; -.
DR Ensembl; ENSMUST00000020980; ENSMUSP00000020980; ENSMUSG00000020649.
DR GeneID; 20135; -.
DR KEGG; mmu:20135; -.
DR UCSC; uc007ner.2; mouse.
DR CTD; 6241; -.
DR MGI; MGI:98181; Rrm2.
DR VEuPathDB; HostDB:ENSMUSG00000020649; -.
DR eggNOG; KOG1567; Eukaryota.
DR GeneTree; ENSGT00390000013305; -.
DR InParanoid; P11157; -.
DR OMA; KVGEYQR; -.
DR OrthoDB; 1277at2759; -.
DR PhylomeDB; P11157; -.
DR TreeFam; TF300465; -.
DR BRENDA; 1.17.4.1; 3474.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR BioGRID-ORCS; 20135; 25 hits in 72 CRISPR screens.
DR ChiTaRS; Rrm2; mouse.
DR EvolutionaryTrace; P11157; -.
DR PRO; PR:P11157; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P11157; protein.
DR Bgee; ENSMUSG00000020649; Expressed in gastrula and 232 other tissues.
DR ExpressionAtlas; P11157; baseline and differential.
DR Genevisible; P11157; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IDA:CAFA.
DR GO; GO:0008199; F:ferric iron binding; IDA:CAFA.
DR GO; GO:0042802; F:identical protein binding; IMP:CAFA.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IDA:UniProtKB.
DR GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; IDA:ComplexPortal.
DR GO; GO:0001824; P:blastocyst development; IMP:MGI.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009262; P:deoxyribonucleotide metabolic process; IDA:MGI.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR GO; GO:0000278; P:mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0051290; P:protein heterotetramerization; IPI:UniProtKB.
DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; IEA:Ensembl.
DR GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; IDA:ComplexPortal.
DR CDD; cd01049; RNRR2; 1.
DR DisProt; DP00462; -.
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; Cytoplasm; Deoxyribonucleotide synthesis; Iron;
KW Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..390
FT /note="Ribonucleoside-diphosphate reductase subunit M2"
FT /id="PRO_0000190450"
FT MOTIF 49..51
FT /note="Cy"
FT /evidence="ECO:0000250|UniProtKB:P31350"
FT ACT_SITE 177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 139
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT BINDING 170
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT BINDING 170
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT BINDING 173
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT BINDING 233
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT BINDING 267
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT BINDING 267
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT BINDING 270
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:1XSM"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:1W68"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 89..100
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 113..119
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 122..148
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 157..184
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 188..195
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 202..216
FT /evidence="ECO:0007829|PDB:1H0O"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 222..249
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 254..279
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 287..306
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 311..314
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 318..335
FT /evidence="ECO:0007829|PDB:1H0O"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:1H0O"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:1AFT"
SQ SEQUENCE 390 AA; 45096 MW; AC7ACC4FAF8A4A2F CRC64;
MLSVRTPLAT IADQQQLQLS PLKRLTLADK ENTPPTLSST RVLASKAARR IFQDSAELES
KAPTNPSVED EPLLRENPRR FVVFPIEYHD IWQMYKKAEA SFWTAEEVDL SKDIQHWEAL
KPDERHFISH VLAFFAASDG IVNENLVERF SQEVQVTEAR CFYGFQIAME NIHSEMYSLL
IDTYIKDPKE REYLFNAIET MPCVKKKADW ALRWIGDKEA TYGERVVAFA AVEGIFFSGS
FASIFWLKKR GLMPGLTFSN ELISRDEGLH CDFACLMFKH LVHKPAEQRV REIITNAVRI
EQEFLTEALP VKLIGMNCTL MKQYIEFVAD RLMLELGFNK IFRVENPFDF MENISLEGKT
NFFEKRVGEY QRMGVMSNST ENSFTLDADF
