RIR2_RAT
ID RIR2_RAT Reviewed; 390 AA.
AC Q4KLN6;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 127.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides (By similarity). Inhibits Wnt signaling
CC (By similarity). {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; Evidence={ECO:0000250};
CC Note=Binds 2 iron ions per subunit. {ECO:0000250};
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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small
CC chain family. {ECO:0000305}.
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DR EMBL; BC099082; AAH99082.1; -; mRNA.
DR RefSeq; NP_001020911.1; NM_001025740.1.
DR AlphaFoldDB; Q4KLN6; -.
DR SMR; Q4KLN6; -.
DR STRING; 10116.ENSRNOP00000037227; -.
DR iPTMnet; Q4KLN6; -.
DR PhosphoSitePlus; Q4KLN6; -.
DR jPOST; Q4KLN6; -.
DR PaxDb; Q4KLN6; -.
DR PRIDE; Q4KLN6; -.
DR GeneID; 362720; -.
DR KEGG; rno:362720; -.
DR CTD; 6241; -.
DR RGD; 1598310; Rrm2.
DR VEuPathDB; HostDB:ENSRNOG00000054286; -.
DR eggNOG; KOG1567; Eukaryota.
DR HOGENOM; CLU_035339_2_1_1; -.
DR InParanoid; Q4KLN6; -.
DR OMA; PQLWEMY; -.
DR OrthoDB; 680824at2759; -.
DR PhylomeDB; Q4KLN6; -.
DR TreeFam; TF300465; -.
DR UniPathway; UPA00326; -.
DR PRO; PR:Q4KLN6; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000054286; Expressed in thymus and 18 other tissues.
DR Genevisible; Q4KLN6; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IDA:RGD.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; ISO:RGD.
DR GO; GO:0008199; F:ferric iron binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; ISS:UniProtKB.
DR GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; ISO:RGD.
DR GO; GO:0001824; P:blastocyst development; ISO:RGD.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009262; P:deoxyribonucleotide metabolic process; ISO:RGD.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR GO; GO:0000278; P:mitotic cell cycle; IEP:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0051290; P:protein heterotetramerization; ISO:RGD.
DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; IEP:RGD.
DR GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; ISO:RGD.
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 SUPFAM; SSF47240; SSF47240; 1.
DR PROSITE; PS00368; RIBORED_SMALL; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Deoxyribonucleotide synthesis; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..390
FT /note="Ribonucleoside-diphosphate reductase subunit M2"
FT /id="PRO_0000190451"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 170
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 170
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 233
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 267
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10014"
FT BINDING 267
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 270
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11157"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P11157"
SQ SEQUENCE 390 AA; 45039 MW; A1BD4EABB7920F69 CRC64;
MLSVRAPLAT IADQQQLHLS PLKRLSLADK ENTPPTLSSA RVLASKAARR IFQDSAELES
KAPTKPSIEE EPLLRENPRR FVVFPIEYHD IWQMYKKAEA SFWTAEEVDL SKDIQHWEAL
KPDERHFISH VLAFFAASDG IVNENLVERF SQEVQVTEAR CFYGFQIAME NIHSEMYSLL
IDTYIKDSKE REYLFNAIET MPCVKKKADW ALRWIGDKEA TYGERVVAFA AVEGIFFSGS
FASIFWLKKR GLMPGLTFSN ELISRDEGLH CDFACLMFKH LVHKPSEQRV KEIITNSVRI
EQEFLTEALP VKLIGMNCTL MKQYIEFVAD RLMLELGFNK IFKVENPFDF MENISLEGKT
NFFEKRVGEY QRMGVMSNST ENSFTLDADF
