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P21524 (RIR1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 chain 1

EC=1.17.4.1
Alternative name(s):
Ribonucleotide reductase R1 subunit 1
Ribonucleotide reductase large subunit 1
Gene names
Name:RNR1
Synonyms:CRT7, RIR1, SDS12
Ordered Locus Names:YER070W
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length888 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. Ref.7

Catalytic activity

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

Enzyme regulation

Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the R1 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. Inhibited by SML1. Ref.5

Pathway

Genetic information processing; DNA replication.

Subunit structure

Heterotetramer of two large (R1) and two small (R2) subunits. S.cerevisiae has two different R1 subunits (RNR1 and RNR3) and two different R2 subunits (RNR2 and RNR4). The functional form of the small subunits is a RNR2-RNR4 heterodimer, where RNR2 provides the iron-radical center and RNR4 is required for proper folding of RNR2 and assembly with the large subunits. Under normal growth conditions, the active form of the large subunits is a homodimer of the constitutively expressed RNR1. In damaged cells or cells arrested for DNA synthesis, the reductase consists of multiple species because of the association of the small subunits (RNR2-RNR4) with either the RNR1 homodimer or a heterodimer of RNR1 and the damage-inducible RNR3. RNR1 interacts with the ribonucleotide reductase inhibitor SML1. Ref.5 Ref.6 Ref.14 Ref.15

Subcellular location

Cytoplasm Ref.9.

Induction

Cell cycle-regulated with highest activity in S phase. Moderately induced by DNA-damage. Ref.3 Ref.5

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 R1, is formed only in the presence of the second subunit R2 By similarity.

Present with 293000 molecules/cell in log phase SD medium.

Sequence similarities

Belongs to the ribonucleoside diphosphate reductase large chain family.

Contains 1 ATP-cone domain.

Biophysicochemical properties

Kinetic parameters:

Vmax=2250 nmol/min/mg enzyme for cytidine 5'-diphosphate Ref.6

Temperature dependence:

Optimum temperature is 30 degrees Celsius.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 888888Ribonucleoside-diphosphate reductase large chain 1
PRO_0000187203

Regions

Domain1 – 9292ATP-cone
Region11 – 177Allosteric activator binding By similarity
Region217 – 2182Substrate binding
Region285 – 2884Allosteric effector binding, determines substrate specificity
Region426 – 4305Substrate binding
Region607 – 6115Substrate binding

Sites

Active site4261Proton acceptor
Active site4281Cysteine radical intermediate
Active site4301Proton acceptor
Binding site51Allosteric activator By similarity
Binding site531Allosteric activator By similarity
Binding site881Allosteric activator By similarity
Binding site2021Substrate
Binding site2471Substrate; via amide nitrogen
Site2181Important for hydrogen atom transfer By similarity
Site2261Allosteric effector binding, determines substrate specificity
Site2561Allosteric effector binding, determines substrate specificity
Site4431Important for hydrogen atom transfer By similarity
Site7411Important for electron transfer By similarity
Site7421Important for electron transfer By similarity
Site8831Interacts with thioredoxin/glutaredoxin By similarity
Site8861Interacts with thioredoxin/glutaredoxin By similarity

Amino acid modifications

Modified residue2271Phosphoserine Ref.10
Modified residue8371Phosphoserine Ref.10
Modified residue8871Phosphoserine Ref.10 Ref.11
Disulfide bond218 ↔ 443Redox-active Ref.13

Experimental info

Mutagenesis4281C → A: Completely abolishes reductase activity. Ref.7
Sequence conflict3291F → L in CAA49151. Ref.4
Sequence conflict587 – 5893TLR → NLK in CAA49150. Ref.4
Sequence conflict6661Q → E no nucleotide entry Ref.3
Sequence conflict6791E → Q no nucleotide entry Ref.3

Secondary structure

............................................................................................................................................... 888
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P21524 [UniParc].

Last modified February 1, 1995. Version 2.
Checksum: 56BE1B077916E419

FASTA88899,561
        10         20         30         40         50         60 
MYVYKRDGRK EPVQFDKITA RISRLCYGLD PKHIDAVKVT QRIISGVYEG VTTIELDNLA 

        70         80         90        100        110        120 
AETCAYMTTV HPDYATLAAR IAISNLHKQT TKQFSKVVED LYRYVNAATG KPAPMISDDV 

       130        140        150        160        170        180 
YNIVMENKDK LNSAIVYDRD FQYSYFGFKT LERSYLLRIN GQVAERPQHL IMRVALGIHG 

       190        200        210        220        230        240 
RDIEAALETY NLMSLKYFTH ASPTLFNAGT PKPQMSSCFL VAMKEDSIEG IYDTLKECAL 

       250        260        270        280        290        300 
ISKTAGGIGL HIHNIRSTGS YIAGTNGTSN GLIPMIRVFN NTARYVDQGG NKRPGAFALY 

       310        320        330        340        350        360 
LEPWHADIFD FIDIRKNHGK EEIRARDLFP ALWIPDLFMK RVEENGTWTL FSPTSAPGLS 

       370        380        390        400        410        420 
DCYGDEFEAL YTRYEKEGRG KTIKAQKLWY SILEAQTETG TPFVVYKDAC NRKSNQKNLG 

       430        440        450        460        470        480 
VIKSSNLCCE IVEYSAPDET AVCNLASVAL PAFIETSEDG KTSTYNFKKL HEIAKVVTRN 

       490        500        510        520        530        540 
LNRVIDRNYY PVEEARKSNM RHRPIALGVQ GLADTFMLLR LPFDSEEARL LNIQIFETIY 

       550        560        570        580        590        600 
HASMEASCEL AQKDGPYETF QGSPASQGIL QFDMWDQKPY GMWDWDTLRK DIMKHGVRNS 

       610        620        630        640        650        660 
LTMAPMPTAS TSQILGYNEC FEPVTSNMYS RRVLSGEFQV VNPYLLRDLV DLGIWDEGMK 

       670        680        690        700        710        720 
QYLITQNGSI QGLPNVPQEL KDLYKTVWEI SQKTIINMAA DRSVYIDQSH SLNLFLRAPT 

       730        740        750        760        770        780 
MGKLTSMHFY GWKKGLKTGM YYLRTQAASA AIQFTIDQKI ADQATENVAD ISNLKRPSYM 

       790        800        810        820        830        840 
PSSASYAASD FVPAAVTANA TIPSLDSSSE ASREASPAPT GSHSLTKGMA ELNVQESKVE 

       850        860        870        880 
VPEVPAPTKN EEKAAPIVDD EETEFDIYNS KVIACAIDNP EACEMCSG 

« Hide

References

« Hide 'large scale' references
[1]"The nucleotide sequence of Saccharomyces cerevisiae chromosome V."
Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E., Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S., Hyman R.W. expand/collapse author list , Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X., Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y., Botstein D., Davis R.W.
Nature 387:78-81(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[2]"The reference genome sequence of Saccharomyces cerevisiae: Then and now."
Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.
G3 (Bethesda) 4:389-398(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[3]"Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase."
Elledge S.J., Davis R.W.
Genes Dev. 4:740-751(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-100 AND 653-682, INDUCTION.
[4]"Use of synthetic lethal mutants to clone and characterize a novel CTP synthetase gene in Saccharomyces cerevisiae."
Ozier-Kalogeropoulos O., Adeline M.-T., Yang W.-L., Carman G.M., Lacroute F.
Mol. Gen. Genet. 242:431-439(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 313-384 AND 546-590.
[5]"Yeast Sml1, a protein inhibitor of ribonucleotide reductase."
Chabes A., Domkin V., Thelander L.
J. Biol. Chem. 274:36679-36683(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SML1, ENZYME REGULATION.
[6]"Yeast ribonucleotide reductase has a heterodimeric iron-radical-containing subunit."
Chabes A., Domkin V., Larsson G., Liu A., Graeslund A., Wijmenga S., Thelander L.
Proc. Natl. Acad. Sci. U.S.A. 97:2474-2479(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES.
[7]"Yeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex."
Domkin V., Thelander L., Chabes A.
J. Biol. Chem. 277:18574-18578(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-428.
[8]"Global analysis of protein expression in yeast."
Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S.
Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[9]"Subcellular localization of yeast ribonucleotide reductase regulated by the DNA replication and damage checkpoint pathways."
Yao R., Zhang Z., An X., Bucci B., Perlstein D.L., Stubbe J., Huang M.
Proc. Natl. Acad. Sci. U.S.A. 100:6628-6633(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"A multidimensional chromatography technology for in-depth phosphoproteome analysis."
Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227; SER-837 AND SER-887, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution."
Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.
Science 325:1682-1686(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-887, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Sites of ubiquitin attachment in Saccharomyces cerevisiae."
Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.
Proteomics 12:236-240(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation."
Xu H., Faber C., Uchiki T., Fairman J.W., Racca J., Dealwis C.
Proc. Natl. Acad. Sci. U.S.A. 103:4022-4027(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEXES WITH CDP; UDP; TTP; GDP; GTP; ADP AND AMPPNP, DISULFIDE BOND.
[14]"Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly."
Xu H., Faber C., Uchiki T., Racca J., Dealwis C.
Proc. Natl. Acad. Sci. U.S.A. 103:4028-4033(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH GEMCITABINE DIPHOSPHATE AND R2 PEPTIDES, SUBUNIT.
[15]"The structural basis for peptidomimetic inhibition of eukaryotic ribonucleotide reductase: a conformationally flexible pharmacophore."
Xu H., Fairman J.W., Wijerathna S.R., Kreischer N.R., LaMacchia J., Helmbrecht E., Cooperman B.S., Dealwis C.
J. Med. Chem. 51:4653-4659(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) IN COMPLEX WITH PEPTIDE INHIBITORS, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U18813 Genomic DNA. Translation: AAB64606.1.
X69216 Genomic DNA. Translation: CAA49150.1.
X69217 Genomic DNA. Translation: CAA49151.1.
BK006939 Genomic DNA. Translation: DAA07729.1.
PIRS50573.
RefSeqNP_010993.1. NM_001178961.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZYZX-ray2.90A/B1-888[»]
1ZZDX-ray2.60A1-888[»]
2CVSX-ray2.60A1-888[»]
2CVTX-ray3.20A1-888[»]
2CVUX-ray2.90A1-888[»]
2CVVX-ray2.90A1-888[»]
2CVWX-ray2.40A1-888[»]
2CVXX-ray2.20A1-888[»]
2CVYX-ray2.40A1-888[»]
2EUDX-ray2.30A1-888[»]
2ZLFX-ray2.59A1-888[»]
2ZLGX-ray2.52A1-888[»]
3K8TX-ray2.10A1-888[»]
3PAWX-ray6.61A/B/C/D1-888[»]
3RSRX-ray2.30A1-888[»]
3S87X-ray2.25A1-888[»]
3S8AX-ray2.90A1-888[»]
3S8BX-ray2.80A1-888[»]
3S8CX-ray2.77A1-888[»]
3TB9X-ray2.53A1-888[»]
3TBAX-ray2.80A1-888[»]
ProteinModelPortalP21524.
SMRP21524. Positions 15-796.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid36813. 59 interactions.
DIPDIP-6299N.
IntActP21524. 10 interactions.
MINTMINT-680321.
STRING4932.YER070W.

Proteomic databases

MaxQBP21524.
PaxDbP21524.
PeptideAtlasP21524.
PRIDEP21524.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYER070W; YER070W; YER070W.
GeneID856801.
KEGGsce:YER070W.

Organism-specific databases

CYGDYER070w.
SGDS000000872. RNR1.

Phylogenomic databases

eggNOGCOG0209.
GeneTreeENSGT00750000117986.
HOGENOMHOG000057035.
KOK10807.
OMAANGSIQH.
OrthoDBEOG7C5MHR.

Enzyme and pathway databases

BioCycMetaCyc:YER070W-MONOMER.
YEAST:YER070W-MONOMER.
UniPathwayUPA00326.

Gene expression databases

GenevestigatorP21524.

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

EvolutionaryTraceP21524.
NextBio983047.

Entry information

Entry nameRIR1_YEAST
AccessionPrimary (citable) accession number: P21524
Secondary accession number(s): D3DLX5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: February 1, 1995
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome V

Yeast (Saccharomyces cerevisiae) chromosome V: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways