RIR1_MOUSE
ID RIR1_MOUSE Reviewed; 792 AA.
AC P07742; Q91YM8;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleoside-diphosphate reductase subunit M1;
DE AltName: Full=Ribonucleotide reductase large subunit;
GN Name=Rrm1;
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=2581962; DOI=10.1016/s0021-9258(18)88881-0;
RA Caras I.W., Levinson B.B., Fabry M., Williams S.R., Martin D.W. Jr.;
RT "Cloned mouse ribonucleotide reductase subunit M1 cDNA reveals amino acid
RT sequence homology with Escherichia coli and herpesvirus ribonucleotide
RT reductases.";
RL J. Biol. Chem. 260:7015-7022(1985).
RN [2]
RP SEQUENCE REVISION.
RA Caras I.W.;
RL Submitted (AUG-1985) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, Embryonic 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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [6]
RP CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=19176520; DOI=10.1074/jbc.m809338200;
RA Avval F.Z., Holmgren A.;
RT "Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors
RT for mammalian S phase ribonucleotide reductase.";
RL J. Biol. Chem. 284:8233-8240(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides.
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:0000269|PubMed:19176520};
CC -!- ACTIVITY REGULATION: Under complex allosteric control mediated by
CC deoxynucleoside triphosphates and ATP binding to separate specificity
CC and activation sites on the M1 subunit. The type of nucleotide bound at
CC the specificity site determines substrate preference. It seems probable
CC that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction
CC and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP
CC binding to the activity site, the dATP inhibition is mediated by AHCYL1
CC which stabilizes dATP in the site (By similarity).
CC {ECO:0000250|UniProtKB:P23921}.
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Heterodimer of a large and a small subunit. Interacts with
CC RRM2B. Interacts with AHCYL1 which inhibits its activity (By
CC similarity). {ECO:0000250|UniProtKB:P23921}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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 -!- MISCELLANEOUS: The level of the enzyme activity is closely correlated
CC with the growth rate of a cell and appears to vary with the cell cycle.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
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DR EMBL; K02927; AAA40061.1; -; mRNA.
DR EMBL; AK088043; BAC40112.1; -; mRNA.
DR EMBL; AK137075; BAE23230.1; -; mRNA.
DR EMBL; AK168586; BAE40455.1; -; mRNA.
DR EMBL; CH466531; EDL16602.1; -; Genomic_DNA.
DR EMBL; BC016450; AAH16450.1; -; mRNA.
DR CCDS; CCDS40049.1; -.
DR PIR; A24050; A24050.
DR RefSeq; NP_033129.2; NM_009103.3.
DR AlphaFoldDB; P07742; -.
DR SMR; P07742; -.
DR BioGRID; 203022; 6.
DR ComplexPortal; CPX-370; Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant.
DR ComplexPortal; CPX-371; Ribonucleoside-diphosphate reductase RR1 complex, RRM2B variant.
DR IntAct; P07742; 1.
DR STRING; 10090.ENSMUSP00000033283; -.
DR BindingDB; P07742; -.
DR ChEMBL; CHEMBL3739; -.
DR iPTMnet; P07742; -.
DR PhosphoSitePlus; P07742; -.
DR EPD; P07742; -.
DR jPOST; P07742; -.
DR MaxQB; P07742; -.
DR PaxDb; P07742; -.
DR PeptideAtlas; P07742; -.
DR PRIDE; P07742; -.
DR ProteomicsDB; 253324; -.
DR Antibodypedia; 10853; 671 antibodies from 38 providers.
DR DNASU; 20133; -.
DR Ensembl; ENSMUST00000033283; ENSMUSP00000033283; ENSMUSG00000030978.
DR GeneID; 20133; -.
DR KEGG; mmu:20133; -.
DR UCSC; uc009irp.2; mouse.
DR CTD; 6240; -.
DR MGI; MGI:98180; Rrm1.
DR VEuPathDB; HostDB:ENSMUSG00000030978; -.
DR eggNOG; KOG1112; Eukaryota.
DR GeneTree; ENSGT00910000144246; -.
DR HOGENOM; CLU_000404_1_0_1; -.
DR InParanoid; P07742; -.
DR OMA; RGSIQNI; -.
DR OrthoDB; 156716at2759; -.
DR PhylomeDB; P07742; -.
DR TreeFam; TF300578; -.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR BioGRID-ORCS; 20133; 27 hits in 66 CRISPR screens.
DR ChiTaRS; Rrm1; mouse.
DR PRO; PR:P07742; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P07742; protein.
DR Bgee; ENSMUSG00000030978; Expressed in fetal liver hematopoietic progenitor cell and 277 other tissues.
DR ExpressionAtlas; P07742; baseline and differential.
DR Genevisible; P07742; MM.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0017076; F:purine nucleotide binding; IDA:MGI.
DR GO; GO:0061731; F:ribonucleoside-diphosphate reductase activity; ISO:MGI.
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:0009263; P:deoxyribonucleotide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISO:MGI.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IC:ComplexPortal.
DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:ComplexPortal.
DR GO; GO:0070318; P:positive regulation of G0 to G1 transition; IDA:ComplexPortal.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0010971; P:positive regulation of G2/M 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 InterPro; IPR005144; ATP-cone_dom.
DR InterPro; IPR013346; NrdE_NrdA.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR008926; RNR_R1-su_N.
DR InterPro; IPR039718; Rrm1.
DR PANTHER; PTHR11573; PTHR11573; 1.
DR Pfam; PF03477; ATP-cone; 1.
DR Pfam; PF02867; Ribonuc_red_lgC; 1.
DR Pfam; PF00317; Ribonuc_red_lgN; 1.
DR PRINTS; PR01183; RIBORDTASEM1.
DR SUPFAM; SSF48168; SSF48168; 1.
DR TIGRFAMs; TIGR02506; NrdE_NrdA; 1.
DR PROSITE; PS51161; ATP_CONE; 1.
DR PROSITE; PS00089; RIBORED_LARGE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm;
KW Deoxyribonucleotide synthesis; Disulfide bond; Nucleotide-binding;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..792
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187191"
FT DOMAIN 1..92
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT ACT_SITE 427
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 429
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 431
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 5..6
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 11..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 57
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 202
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 217
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 226..228
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 243
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 256
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 263..264
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 427
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 431
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 604..607
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT SITE 218
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 444
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 737
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 738
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 787
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 790
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT MOD_RES 17
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT MOD_RES 376
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT MOD_RES 751
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT DISULFID 218..444
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT CONFLICT 202
FT /note="S -> P (in Ref. 1; AAA40061)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 792 AA; 90210 MW; 051C6CE407D24C69 CRC64;
MHVIKRDGRQ ERVMFDKITS RIQKLCYGLN MDFVDPAQIT MKVIQGLYSG VTTVELDTLA
AETAATLTTK HPDYAILAAR IAVSNLHKET KKVFSDVMED LYNYINPHNG RHSPMVASST
LDIVMANKDR LNSAIIYDRD FSYNYFGFKT LERSYLLKIN GKVAERPQHM LMRVSVGIHK
EDIDAAIETY NLLSEKWFTH ASPTLFNAGT NRPQLSSCFL LSMKDDSIEG IYDTLKQCAL
ISKSAGGIGV AVSCIRATGS YIAGTNGNSN GLVPMLRVYN NTARYVDQGG NKRPGAFAIY
LEPWHLDIFE FLDLKKNTGK EEQRARDLFF ALWIPDLFMK RVETNQDWSL MCPNECPGLD
EVWGEEFEKL YESYEKQGRV RKVVKAQQLW YAIIESQTET GTPYMLYKDS CNRKSNQQNL
GTIKCSNLCT EIVEYTSKDE VAVCNLASLA LNMYVTPEHT YDFEKLAEVT KVIVRNLNKI
IDINYYPIPE AHLSNKRHRP IGIGVQGLAD AFILMRYPFE SPEAQLLNKQ IFETIYYGAL
EASCELAKEY GPYETYEGSP VSKGILQYDM WNVAPTDLWD WKPLKEKIAK YGIRNSLLIA
PMPTASTAQI LGNNESIEPY TSNIYTRRVL SGEFQIVNPH LLKDLTERGL WNEEMKNQII
ACNGSIQSIP EIPDDLKQLY KTVWEISQKT VLKMAAERGA FIDQSQSLNI HIAEPNYGKL
TSMHFYGWKQ GLKTGMYYLR TRPAANPIQF TLNKEKLKDK EKALKEEEEK ERNTAAMVCS
LENREECLMC GS
