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P07742 (RIR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ribonucleoside-diphosphate reductase large subunit

EC=1.17.4.1
Alternative name(s):
Ribonucleoside-diphosphate reductase subunit M1
Ribonucleotide reductase large subunit
Gene names
Name:Rrm1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length792 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.

Catalytic activity

2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin. Ref.6

Enzyme regulation

Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site By similarity.

Pathway

Genetic information processing; DNA replication.

Subunit structure

Heterodimer of a large and a small subunit. Interacts with RRM2B By similarity. Ref.6

Subcellular location

Cytoplasm.

Miscellaneous

Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2.

The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.

Sequence similarities

Belongs to the ribonucleoside diphosphate reductase large chain family.

Contains 1 ATP-cone domain.

Ontologies

Keywords
   Biological processDNA replication
   Cellular componentCytoplasm
   LigandATP-binding
Nucleotide-binding
   Molecular functionOxidoreductase
   PTMAcetylation
Disulfide bond
   Technical termAllosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from electronic annotation. Source: UniProtKB-UniPathway

cell proliferation in forebrain

Inferred from electronic annotation. Source: Ensembl

deoxyribonucleotide biosynthetic process

Inferred from direct assay Ref.6. Source: UniProtKB

male gonad development

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

protein heterotetramerization

Inferred from physical interaction Ref.6. Source: UniProtKB

protein oligomerization

Inferred from physical interaction PubMed 16861739. Source: MGI

pyrimidine nucleobase metabolic process

Inferred from electronic annotation. Source: Ensembl

response to ionizing radiation

Inferred from electronic annotation. Source: Ensembl

retina development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell projection

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nuclear envelope

Inferred from electronic annotation. Source: Ensembl

ribonucleoside-diphosphate reductase complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 16829694. Source: MGI

purine nucleotide binding

Inferred from direct assay PubMed 16861739. Source: MGI

ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor

Inferred from direct assay Ref.6. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 792792Ribonucleoside-diphosphate reductase large subunit
PRO_0000187191

Regions

Domain1 – 9292ATP-cone
Region11 – 177Allosteric activator binding By similarity
Region217 – 2182Substrate binding By similarity
Region285 – 2884Allosteric effector binding, determines substrate specificity By similarity
Region427 – 4315Substrate binding By similarity
Region603 – 6075Substrate binding By similarity

Sites

Active site4271Proton acceptor By similarity
Active site4291Cysteine radical intermediate By similarity
Active site4311Proton acceptor By similarity
Binding site51Allosteric activator By similarity
Binding site531Allosteric activator By similarity
Binding site881Allosteric activator By similarity
Binding site2471Substrate; via amide nitrogen By similarity
Site2181Important for hydrogen atom transfer By similarity
Site2261Allosteric effector binding, determines substrate specificity By similarity
Site2561Allosteric effector binding, determines substrate specificity By similarity
Site4441Important for hydrogen atom transfer By similarity
Site7371Important for electron transfer By similarity
Site7381Important for electron transfer By similarity
Site7871Interacts with thioredoxin/glutaredoxin By similarity
Site7901Interacts with thioredoxin/glutaredoxin By similarity

Amino acid modifications

Modified residue171N6-acetyllysine By similarity
Modified residue3761N6-acetyllysine By similarity
Disulfide bond218 ↔ 444Redox-active By similarity

Experimental info

Sequence conflict2021S → P in AAA40061. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P07742 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 051C6CE407D24C69

FASTA79290,210
        10         20         30         40         50         60 
MHVIKRDGRQ ERVMFDKITS RIQKLCYGLN MDFVDPAQIT MKVIQGLYSG VTTVELDTLA 

        70         80         90        100        110        120 
AETAATLTTK HPDYAILAAR IAVSNLHKET KKVFSDVMED LYNYINPHNG RHSPMVASST 

       130        140        150        160        170        180 
LDIVMANKDR LNSAIIYDRD FSYNYFGFKT LERSYLLKIN GKVAERPQHM LMRVSVGIHK 

       190        200        210        220        230        240 
EDIDAAIETY NLLSEKWFTH ASPTLFNAGT NRPQLSSCFL LSMKDDSIEG IYDTLKQCAL 

       250        260        270        280        290        300 
ISKSAGGIGV AVSCIRATGS YIAGTNGNSN GLVPMLRVYN NTARYVDQGG NKRPGAFAIY 

       310        320        330        340        350        360 
LEPWHLDIFE FLDLKKNTGK EEQRARDLFF ALWIPDLFMK RVETNQDWSL MCPNECPGLD 

       370        380        390        400        410        420 
EVWGEEFEKL YESYEKQGRV RKVVKAQQLW YAIIESQTET GTPYMLYKDS CNRKSNQQNL 

       430        440        450        460        470        480 
GTIKCSNLCT EIVEYTSKDE VAVCNLASLA LNMYVTPEHT YDFEKLAEVT KVIVRNLNKI 

       490        500        510        520        530        540 
IDINYYPIPE AHLSNKRHRP IGIGVQGLAD AFILMRYPFE SPEAQLLNKQ IFETIYYGAL 

       550        560        570        580        590        600 
EASCELAKEY GPYETYEGSP VSKGILQYDM WNVAPTDLWD WKPLKEKIAK YGIRNSLLIA 

       610        620        630        640        650        660 
PMPTASTAQI LGNNESIEPY TSNIYTRRVL SGEFQIVNPH LLKDLTERGL WNEEMKNQII 

       670        680        690        700        710        720 
ACNGSIQSIP EIPDDLKQLY KTVWEISQKT VLKMAAERGA FIDQSQSLNI HIAEPNYGKL 

       730        740        750        760        770        780 
TSMHFYGWKQ GLKTGMYYLR TRPAANPIQF TLNKEKLKDK EKALKEEEEK ERNTAAMVCS 

       790 
LENREECLMC GS 

« Hide

References

« Hide 'large scale' references
[1]"Cloned mouse ribonucleotide reductase subunit M1 cDNA reveals amino acid sequence homology with Escherichia coli and herpesvirus ribonucleotide reductases."
Caras I.W., Levinson B.B., Fabry M., Williams S.R., Martin D.W. Jr.
J. Biol. Chem. 260:7015-7022(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Caras I.W.
Submitted (AUG-1985) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Embryo, Embryonic liver and Thymus.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary tumor.
[6]"Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for mammalian S phase ribonucleotide reductase."
Avval F.Z., Holmgren A.
J. Biol. Chem. 284:8233-8240(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K02927 mRNA. Translation: AAA40061.1.
AK088043 mRNA. Translation: BAC40112.1.
AK137075 mRNA. Translation: BAE23230.1.
AK168586 mRNA. Translation: BAE40455.1.
CH466531 Genomic DNA. Translation: EDL16602.1.
BC016450 mRNA. Translation: AAH16450.1.
CCDSCCDS40049.1.
PIRA24050.
RefSeqNP_033129.2. NM_009103.3.
UniGeneMm.197486.
Mm.415177.

3D structure databases

ProteinModelPortalP07742.
SMRP07742. Positions 14-742.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203022. 4 interactions.
IntActP07742. 1 interaction.
MINTMINT-4121992.

Chemistry

BindingDBP07742.
ChEMBLCHEMBL3739.

PTM databases

PhosphoSiteP07742.

Proteomic databases

MaxQBP07742.
PaxDbP07742.
PRIDEP07742.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033283; ENSMUSP00000033283; ENSMUSG00000030978.
GeneID20133.
KEGGmmu:20133.
UCSCuc009irp.2. mouse.

Organism-specific databases

CTD6240.
MGIMGI:98180. Rrm1.

Phylogenomic databases

eggNOGCOG0209.
GeneTreeENSGT00390000001372.
HOGENOMHOG000057035.
HOVERGENHBG003447.
InParanoidQ91YM8.
KOK10807.
OMALLWQMPS.
OrthoDBEOG7BGHK2.
TreeFamTF300578.

Enzyme and pathway databases

UniPathwayUPA00326.

Gene expression databases

BgeeP07742.
CleanExMM_RRM1.
GenevestigatorP07742.

Family and domain databases

InterProIPR005144. ATP-cone.
IPR013346. NrdE_NrdA.
IPR000788. RNR_lg_C.
IPR013509. RNR_lsu_N.
IPR008926. RNR_R1-su_N.
[Graphical view]
PfamPF03477. ATP-cone. 1 hit.
PF02867. Ribonuc_red_lgC. 1 hit.
PF00317. Ribonuc_red_lgN. 1 hit.
[Graphical view]
PRINTSPR01183. RIBORDTASEM1.
SUPFAMSSF48168. SSF48168. 1 hit.
TIGRFAMsTIGR02506. NrdE_NrdA. 1 hit.
PROSITEPS51161. ATP_CONE. 1 hit.
PS00089. RIBORED_LARGE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio297643.
PROP07742.
SOURCESearch...

Entry information

Entry nameRIR1_MOUSE
AccessionPrimary (citable) accession number: P07742
Secondary accession number(s): Q91YM8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot