RIR2B_MOUSE
ID RIR2B_MOUSE Reviewed; 351 AA.
AC Q6PEE3;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Ribonucleoside-diphosphate reductase subunit M2 B;
DE EC=1.17.4.1;
DE AltName: Full=TP53-inducible ribonucleotide reductase M2 B;
DE AltName: Full=p53-inducible ribonucleotide reductase small subunit 2-like protein;
DE Short=p53R2;
GN Name=Rrm2b; Synonyms=P53r2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=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 [2]
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 [3]
RP FUNCTION, AND SUBUNIT.
RX PubMed=11517226; DOI=10.1074/jbc.m106088200;
RA Guittet O., Haakansson P., Voevodskaya N., Fridd S., Graeslund A.,
RA Arakawa H., Nakamura Y., Thelander L.;
RT "Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro
RT with the R1 protein, which is expressed both in resting cells in response
RT to DNA damage and in proliferating cells.";
RL J. Biol. Chem. 276:40647-40651(2001).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12858174; DOI=10.1038/ng1212;
RA Kimura T., Takeda S., Sagiya Y., Gotoh M., Nakamura Y., Arakawa H.;
RT "Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure
RT through attenuation of dNTP pools.";
RL Nat. Genet. 34:440-445(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
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).
CC -!- FUNCTION: Plays a pivotal role in cell survival by repairing damaged
CC DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for
CC DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free
CC radical center required for catalysis. Forms an active ribonucleotide
CC reductase (RNR) complex with RRM1 which is expressed both in resting
CC and proliferating cells in response to DNA damage.
CC {ECO:0000269|PubMed:11517226, ECO:0000269|PubMed:12858174}.
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; Evidence={ECO:0000250};
CC Note=Binds 2 iron ions per subunit. {ECO:0000250};
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Heterotetramer with large (RRM1) subunit. Interacts with
CC p53/TP53. Interacts with RRM1 in response to DNA damage (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Translocates from cytoplasm to nucleus in response to DNA damage.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice develop normally until they are weaned but
CC from then on exhibit growth retardation and early mortality.
CC Pathological examination indicates that multiple organs fail and that
CC they die from severe renal failure by the age of 14 weeks.
CC {ECO:0000269|PubMed:12858174}.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small
CC chain family. {ECO:0000305}.
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DR EMBL; AK138731; BAE23760.1; -; mRNA.
DR EMBL; BC058103; AAH58103.1; -; mRNA.
DR CCDS; CCDS27437.1; -.
DR RefSeq; NP_955770.1; NM_199476.1.
DR AlphaFoldDB; Q6PEE3; -.
DR SMR; Q6PEE3; -.
DR BioGRID; 238573; 2.
DR ComplexPortal; CPX-371; Ribonucleoside-diphosphate reductase RR1 complex, RRM2B variant.
DR STRING; 10090.ENSMUSP00000022901; -.
DR iPTMnet; Q6PEE3; -.
DR PhosphoSitePlus; Q6PEE3; -.
DR EPD; Q6PEE3; -.
DR MaxQB; Q6PEE3; -.
DR PaxDb; Q6PEE3; -.
DR PRIDE; Q6PEE3; -.
DR ProteomicsDB; 253247; -.
DR Antibodypedia; 3483; 363 antibodies from 38 providers.
DR DNASU; 382985; -.
DR Ensembl; ENSMUST00000022901; ENSMUSP00000022901; ENSMUSG00000022292.
DR GeneID; 382985; -.
DR KEGG; mmu:382985; -.
DR UCSC; uc007vnl.1; mouse.
DR CTD; 50484; -.
DR MGI; MGI:2155865; Rrm2b.
DR VEuPathDB; HostDB:ENSMUSG00000022292; -.
DR eggNOG; KOG1567; Eukaryota.
DR GeneTree; ENSGT00390000013305; -.
DR HOGENOM; CLU_035339_2_0_1; -.
DR InParanoid; Q6PEE3; -.
DR OMA; APELQIY; -.
DR OrthoDB; 680824at2759; -.
DR PhylomeDB; Q6PEE3; -.
DR TreeFam; TF300465; -.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR BioGRID-ORCS; 382985; 1 hit in 108 CRISPR screens.
DR ChiTaRS; Rrm2b; mouse.
DR PRO; PR:Q6PEE3; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q6PEE3; protein.
DR Bgee; ENSMUSG00000022292; Expressed in animal zygote and 265 other tissues.
DR ExpressionAtlas; Q6PEE3; baseline and differential.
DR Genevisible; Q6PEE3; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IC:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IC:ComplexPortal.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IDA:MGI.
DR GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; ISO:MGI.
DR GO; GO:0009200; P:deoxyribonucleoside triphosphate metabolic process; IMP:MGI.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IDA:MGI.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IC:ComplexPortal.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:ComplexPortal.
DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IMP:MGI.
DR GO; GO:0070318; P:positive regulation of G0 to G1 transition; IDA:ComplexPortal.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0003014; P:renal system process; IMP:MGI.
DR GO; GO:0014075; P:response to amine; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; ISO:MGI.
DR CDD; cd01049; RNRR2; 1.
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 PIRSF; PIRSF000355; NrdB; 1.
DR SUPFAM; SSF47240; SSF47240; 1.
DR PROSITE; PS00368; RIBORED_SMALL; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Deoxyribonucleotide synthesis; DNA damage; DNA repair; Iron;
KW Metal-binding; Nucleus; Oxidoreductase; Reference proteome.
FT CHAIN 1..351
FT /note="Ribonucleoside-diphosphate reductase subunit M2 B"
FT /id="PRO_0000228152"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 138
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 100
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 131
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 131
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 194
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 231
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
SQ SEQUENCE 351 AA; 40804 MW; 4E1259233C9CC8A9 CRC64;
MGDPERPEAA RPEKGEQLCS ETEENVVRSN EEPLLRKSSR RFVIFPIQYP DIWRMYKQAQ
ASFWTAEEVD LSKDLPHWNK LKSDEKYFIS HILAFFAASD GIVNENLVER FSQEVQVPEA
RCFYGFQILI ENVHSEMYSL LIDTYIRDPK KREFLFNAIE TMPYVKKKAD WALRWIADRK
STFGERVVAF AAVEGIFFSG SFAAIFWLKK RGLMPGLTFS NELISRDEGL HCDFACLMFQ
YLVNKPSEDR VREIIADAVQ IEQEFLTEAL PVGLIGMNCV LMKQYIEFVA DRLLGELGFS
KIFQAENPFD FMENISLEGK TNFFEKRVSE YQRFAVMAET TDNVFTLDAD F
