Ribonucleoside-diphosphate reductase large chain 2 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

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P21672 (RIR3_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 130. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Ribonucleoside-diphosphate reductase large chain 2
EC=1.17.4.1

Alternative name(s):
Ribonucleotide reductase DNA damage-inducible regulatory subunit 2
Ribonucleotide reductase R1 subunit 2
Ribonucleotide reductase large subunit 2

Gene names

Name:	RNR3
Synonyms:	DIN1
Ordered Locus Names:	YIL066C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces ›

Protein attributes

Sequence length	869 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Ref.5
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 large 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	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.
Subcellular location	Cytoplasm Ref.7.
Induction	Highly induced by DNA-damage. Ref.3 Ref.4
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 1364 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family. Contains 1 ATP-cone domain.
Sequence caution	The sequence AAA34569.1 differs from that shown. Reason: Frameshift at positions 127, 129, 130, 247, 250, 287 and 313. The sequence CAA86157.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Oxidoreductase
PTM	Disulfide bond Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from electronic annotation. Source: UniProtKB-UniPathway deoxyribonucleotide biosynthetic process Inferred from direct assay PubMed 5459124. Source: SGD
Cellular_component	mitochondrion Inferred from direct assay PubMed 14576278 PubMed 16823961. Source: SGD ribonucleoside-diphosphate reductase complex Traceable author statement PubMed 10716984. Source: SGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Inferred from direct assay Ref.5. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 869

869

Ribonucleoside-diphosphate reductase large chain 2

PRO_0000187204

Regions

Domain

1 – 92

ATP-cone

Region

11 – 17

Allosteric activator binding By similarity

Region

217 – 218

Substrate binding By similarity

Region

285 – 288

Allosteric effector binding, determines substrate specificity By similarity

Region

426 – 430

Substrate binding By similarity

Region

607 – 611

Substrate binding By similarity

Sites

Active site

426

Proton acceptor By similarity

Active site

428

Cysteine radical intermediate By similarity

Active site

430

Proton acceptor By similarity

Binding site

Allosteric activator By similarity

Binding site

Allosteric activator By similarity

Binding site

Allosteric activator By similarity

Binding site

202

Substrate By similarity

Binding site

247

Substrate; via amide nitrogen By similarity

Site

218

Important for hydrogen atom transfer By similarity

Site

226

Allosteric effector binding, determines substrate specificity By similarity

Site

256

Allosteric effector binding, determines substrate specificity By similarity

Site

443

Important for hydrogen atom transfer By similarity

Site

741

Important for electron transfer By similarity

Site

742

Important for electron transfer By similarity

Site

864

Interacts with thioredoxin/glutaredoxin By similarity

Site

867

Interacts with thioredoxin/glutaredoxin By similarity

Amino acid modifications

Modified residue

799

Phosphoserine Ref.9

Modified residue

806

Phosphoserine Ref.8 Ref.9

Modified residue

810

Phosphoserine Ref.9

Modified residue

866

Phosphoserine Ref.9

Modified residue

868

Phosphoserine Ref.9

Disulfide bond

218 ↔ 443

Redox-active By similarity

Experimental info

Sequence conflict

21 – 22

RI → VL no nucleotide entry Ref.4

Sequence conflict

V → F no nucleotide entry Ref.4

Sequence conflict

N → I no nucleotide entry Ref.4

Sequence conflict

T → H no nucleotide entry Ref.4

Sequence conflict

I → T no nucleotide entry Ref.4

Sequence conflict

212

H → L in AAA34569. Ref.3

Sequence conflict

249

G → V in AAA34569. Ref.3

Sequence conflict

311

F → K in AAA34569. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

P21672 [UniParc].

Last modified February 1, 1995. Version 4.
Checksum: BEE8DEDE41D7049A
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FASTA

869

97,515

        10         20         30         40         50         60 
MYVIKRDGRK EPVQFDKITS RITRLSYGLD PNRIDAVKVT QRIISGVYSG VTTVELDNLA 

        70         80         90        100        110        120 
AETCAYMTTV HPDYATLAAR IAISNLHKQT TKQFSKVIED LHDWINPATG KHAPMISDEI 

       130        140        150        160        170        180 
YNIVMENKDT LNSAIVYDRD FQYTYFGFKT LERSYLLRLN GEVAERPQHL VMRVALGIHG 

       190        200        210        220        230        240 
SDIESVLKTY NLMSLRYFTH ASPTLFNAGT PHPQMSSCFL IAMKDDSIEG IYDTLKECAM 

       250        260        270        280        290        300 
ISKTAGGVGL HINNIRSTGS YIAGTNGTSN GLIPMIRVFN NTARYVDQGG NKRPGAFALF 

       310        320        330        340        350        360 
LEPWHADIFD FVDIRKTHGK EEIRARDLFP ALWIPDLFMK RVQEDGPWTL FSPSAAPGLD 

       370        380        390        400        410        420 
DVWGDEFEEL YTRYEREGRG KTIKAQKLWY AILQAQTETG TPFMVYKDAC NRKTNQQNLG 

       430        440        450        460        470        480 
TIKSSNLCCE IVEYSSPDET AVCNLASIAL PAFVEVSEDG KTASYNFERL HEIAKVITHN 

       490        500        510        520        530        540 
LNRVIDRNYY PVPEARNSNM KHRPIALGVQ GLADTYMMLR LPFESEEAQT LNKQIFETIY 

       550        560        570        580        590        600 
HATLEASCEL AQKEGKYSTF EGSPASKGIL QFDMWNAKPF GMWDWETLRK DIVKHGLRNS 

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

       670        680        690        700        710        720 
QYLITQNGSI QGLPNVPQEL KELYKTVWEI SQKTIINMAA DRAIYIDQSH SLNLFLQAPS 

       730        740        750        760        770        780 
MGKITSMHFY GWKKGLKTGM YYLRTQAASA AIQFTIDQEV ADQAATHIAS VSELDRPVYV 

       790        800        810        820        830        840 
PKGTKFSEQK AASALTESSD NEKDASPVPS EQSSVSSAMS NVKLEDSVAP AVPTETIKED 

       850        860 
SDEKKCDIYN EKVIACTAPT PEACESCSG

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome IX." Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D., Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E., Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C. Barrell B.G. Nature 387:84-87(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	"The DNA damage-inducible gene DIN1 of Saccharomyces cerevisiae encodes a regulatory subunit of ribonucleotide reductase and is identical to RNR3." Yagle K., McEntee K. Mol. Cell. Biol. 10:5553-5557(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-758, INDUCTION.
[4]	"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 1-101 AND 652-711, INDUCTION.
[5]	"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.
[6]	"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].
[7]	"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.
[8]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-806, MASS SPECTROMETRY.
[9]	"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-799; SER-806; SER-810; SER-866 AND SER-868, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z38060 Genomic DNA. Translation: CAA86157.1. Different initiation. M58012 Genomic DNA. Translation: AAA34569.1. Frameshift. BK006942 Genomic DNA. Translation: DAA08484.1.
PIR	WMBY3L. S48413.
RefSeq	NP_012198.3. NM_001179416.3.
3D structure databases
ProteinModelPortal	P21672.
SMR	P21672. Positions 1-787.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2563N.
IntAct	P21672. 12 interactions.
MINT	MINT-425113.
STRING	4932.YIL066C.
Proteomic databases
PaxDb	P21672.
PeptideAtlas	P21672.
PRIDE	P21672.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YIL066C; YIL066C; YIL066C.
GeneID	854744.
KEGG	sce:YIL060W. sce:YIL066C.
Organism-specific databases
CYGD	YIL066c.
SGD	S000001328. RNR3.
Phylogenomic databases
eggNOG	COG0209.
GeneTree	ENSGT00390000001372.
HOGENOM	HOG000057035.
KO	K10807.
OMA	RTPFICQ.
OrthoDB	EOG480N4T.
Enzyme and pathway databases
UniPathway	UPA00326.
Gene expression databases
Genevestigator	P21672.
GermOnline	YIL066C. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR005144. ATP-cone. IPR013346. NrdE_NrdA. IPR000788. RNR_lg_C. IPR013509. RNR_lsu_N. IPR008926. RNR_R1-su_N. [Graphical view]
Pfam	PF03477. ATP-cone. 1 hit. PF02867. Ribonuc_red_lgC. 1 hit. PF00317. Ribonuc_red_lgN. 1 hit. [Graphical view]
PRINTS	PR01183. RIBORDTASEM1.
SUPFAM	SSF48168. Ribonucleo_red_N. 1 hit.
TIGRFAMs	TIGR02506. NrdE_NrdA. 1 hit.
PROSITE	PS51161. ATP_CONE. 1 hit. PS00089. RIBORED_LARGE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	977464.

Entry information

Entry name

RIR3_YEAST

Accession

Primary (citable) accession number: P21672
Secondary accession number(s): D6VVL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	February 1, 1995
Last modified:	April 3, 2013
This is version 130 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program

Relevant documents

Yeast

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

Yeast chromosome IX

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents