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 27-MAR-2024, entry version 207. 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; RC 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 -!- 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}. 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; 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; 5. 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; 10090-ENSMUSP00000020980; -. DR PeptideAtlas; P11157; -. DR ProteomicsDB; 254887; -. DR Pumba; P11157; -. DR Antibodypedia; 26663; 377 antibodies from 36 providers. DR DNASU; 20135; -. DR Ensembl; ENSMUST00000020980.12; ENSMUSP00000020980.6; ENSMUSG00000020649.12. DR GeneID; 20135; -. DR KEGG; mmu:20135; -. DR UCSC; uc007ner.2; mouse. DR AGR; MGI:98181; -. 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; 5487627at2759; -. 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 BioGRID-ORCS; 20135; 25 hits in 77 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 235 other cell types or tissues. DR ExpressionAtlas; P11157; baseline and differential. 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: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:0009185; P:ribonucleoside diphosphate metabolic process; IDA:ComplexPortal. DR CDD; cd01049; RNRR2; 1. DR DisProt; DP00462; -. 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:SF20; 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. DR Genevisible; P11157; MM. 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 //