P49723 (RIR4_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Ribonucleotide reductase R2 subunit 2
Ribonucleotide reductase small subunit 2

Gene names

Name:	RNR4
Synonyms:	CRT3
Ordered Locus Names:	YGR180C

Organism

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

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	345 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. RNR4 is required for proper folding of RNR2 and assembly with the large subunits. Ref.6
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.
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. Interacts with DIF1. Ref.6 Ref.7 Ref.13
Subcellular location	Nucleus. Note: Found predominantly in the nucleus under normal growth conditions and is redistributed to the cytoplasm in damaged cells in a DNA replication and damage checkpoint-dependent manner. Nuclear localization is mediated by DIF1. Ref.9 Ref.13
Induction	Induced by DNA-damage. Ref.1
Miscellaneous	Present with 88884 molecules/cell in log phase SD medium. Lacks 3 iron-binding residues conserved in all other R2 subunits.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase small chain family.
Biophysicochemical properties	Kinetic parameters: Vmax=2250 nmol/min/mg enzyme for cytidine 5'-diphosphate Ref.7 Temperature dependence: Optimum temperature is 30 degrees Celsius.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from electronic annotation. Source: UniProtKB-UniPathway cofactor biosynthetic process Inferred from mutant phenotype PubMed 16285741. Source: SGD deoxyribonucleoside diphosphate metabolic process Inferred from electronic annotation. Source: InterPro deoxyribonucleotide biosynthetic process Inferred from direct assay Ref.6PubMed 5459124. Source: SGD
Cellular_component	nucleus Inferred from direct assay Ref.9PubMed 22842922PubMed 9315670. Source: SGD ribonucleoside-diphosphate reductase complex Inferred from direct assay Ref.7. Source: SGD
Molecular_function	ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Inferred from mutant phenotype Ref.1. Source: SGD transition metal ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNR2	P09938	6	EBI-15251,EBI-15240
WTM1	Q12363	4	EBI-15251,EBI-20563

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 345

345

Ribonucleoside-diphosphate reductase small chain 2

PRO_0000190465

Sites

Active site

131

1

By similarity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.5

Modified residue

55

1

Phosphoserine Ref.11

Modified residue

91

1

Phosphoserine Ref.14

Modified residue

169

1

Phosphoserine Ref.11 Ref.14

Modified residue

330

1

Phosphoserine Ref.14

Modified residue

332

1

Phosphoserine Ref.14

Modified residue

334

1

Phosphothreonine Ref.10 Ref.12 Ref.14

Modified residue

336

1

Phosphoserine Ref.14

Experimental info

Sequence conflict

127

1

Y → H in AAU09736. Ref.4

Secondary structure

1

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345

Helix Strand Turn

Details...

Helix

4 – 9

6

Helix

13 – 21

9

Turn

22 – 24

3

Turn

26 – 28

3

Helix

43 – 54

12

Helix

59 – 61

3

Turn

65 – 67

3

Turn

69 – 73

5

Helix

78 – 89

12

Helix

101 – 107

7

Helix

111 – 138

28

Helix

142 – 144

3

Helix

148 – 151

4

Helix

155 – 166

12

Beta strand

169 – 172

4

Helix

175 – 187

13

Turn

188 – 190

3

Helix

191 – 200

10

Beta strand

202 – 205

4

Helix

207 – 232

26

Helix

240 – 258

19

Turn

265 – 268

4

Helix

277 – 288

12

Helix

316 – 322

7

Sequences

	Sequence		Length	Mass (Da)
	P49723 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 712853F2D87D3972	FASTA	345	40,055
	10 20 30 40 50 60 MEAHNQFLKT FQKERHDMKE AEKDEILLME NSRRFVMFPI KYHEIWAAYK KVEASFWTAE 70 80 90 100 110 120 EIELAKDTED FQKLTDDQKT YIGNLLALSI SSDNLVNKYL IENFSAQLQN PEGKSFYGFQ 130 140 150 160 170 180 IMMENIYSEV YSMMVDAFFK DPKNIPLFKE IANLPEVKHK AAFIERWISN DDSLYAERLV 190 200 210 220 230 240 AFAAKEGIFQ AGNYASMFWL TDKKIMPGLA MANRNICRDR GAYTDFSCLL FAHLRTKPNP 250 260 270 280 290 300 KIIEKIITEA VEIEKEYYSN SLPVEKFGMD LKSIHTYIEF VADGLLQGFG NEKYYNAVNP 310 320 330 340 FEFMEDVATA GKTTFFEKKV SDYQKASDMS KSATPSKEIN FDDDF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Rnr4p, a novel ribonucleotide reductase small-subunit protein." Wang P.J., Chabes A., Casagrande R., Tian X.C., Thelander L., Huffaker T.C. Mol. Cell. Biol. 17:6114-6121(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION. Strain: ATCC 204508 / S288c.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome VII." Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E. , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K. Nature 387:81-84(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	Bienvenut W.V., Peters C. Submitted (JUN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-9; 150-158; 167-178; 219-235 AND 294-312, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT MET-1, MASS SPECTROMETRY.
[6]	"Purification of ribonucleotide reductase subunits Y1, Y2, Y3, and Y4 from yeast: Y4 plays a key role in diiron cluster assembly." Nguyen H.-H.T., Ge J., Perlstein D.L., Stubbe J. Proc. Natl. Acad. Sci. U.S.A. 96:12339-12344(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT.
[7]	"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.
[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]	"Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway." Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M., Jensen O.N. Mol. Cell. Proteomics 4:310-327(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-334, MASS SPECTROMETRY. Strain: YAL6B.
[11]	"Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry." Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F. Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55 AND SER-169, MASS SPECTROMETRY.
[12]	"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 THR-334, MASS SPECTROMETRY.
[13]	"Dif1 is a DNA-damage-regulated facilitator of nuclear import for ribonucleotide reductase." Lee Y.D., Wang J., Stubbe J., Elledge S.J. Mol. Cell 32:70-80(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH DIF1 AND RNR4.
[14]	"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-91; SER-169; SER-330; SER-332; THR-334 AND SER-336, MASS SPECTROMETRY.
[15]	"Structure of the yeast ribonucleotide reductase Y2Y4 heterodimer." Voegtli W.C., Ge J., Perlstein D.L., Stubbe J., Rosenzweig A.C. Proc. Natl. Acad. Sci. U.S.A. 98:10073-10078(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[16]	"Structures of the yeast ribonucleotide reductase Rnr2 and Rnr4 homodimers." Sommerhalter M., Voegtli W.C., Perlstein D.L., Ge J., Stubbe J., Rosenzweig A.C. Biochemistry 43:7736-7742(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U30385 Genomic DNA. Translation: AAB72236.1.
Z72965 Genomic DNA. Translation: CAA97206.1.
AY723819 Genomic DNA. Translation: AAU09736.1.
BK006941 Genomic DNA. Translation: DAA08275.1.

PIR

S59744.

RefSeq

NP_011696.3. NM_001181309.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JK0	X-ray	2.80	B	1-345	[»]
1SMS	X-ray	3.10	A/B	1-345	[»]
1ZZD	X-ray	2.60	B	337-345	[»]

DisProt

DP00488.

ProteinModelPortal

P49723.

SMR

P49723. Positions 3-325.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5381N.

IntAct

P49723. 15 interactions.

MINT

MINT-537732.

STRING

4932.YGR180C.

Proteomic databases

PaxDb

P49723.

PeptideAtlas

P49723.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YGR180C; YGR180C; YGR180C.

GeneID

853091.

KEGG

sce:YGR180C.
sce:YGR187C.

Organism-specific databases

CYGD

YGR180c.

SGD

S000003412. RNR4.

Phylogenomic databases

eggNOG

COG0208.

HOGENOM

HOG000255975.

KO

K10808.

OrthoDB

EOG4DZ55B.

Enzyme and pathway databases

UniPathway

UPA00326.

Gene expression databases

Genevestigator

P49723.

GermOnline

YGR180C. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

1.10.620.20. 1 hit.

InterPro

IPR009078. Ferritin-like_SF.
IPR012348. RNR-rel.
IPR000358. RNR_small.
[Graphical view]

PANTHER

PTHR23409. PTHR23409. 1 hit.

Pfam

PF00268. Ribonuc_red_sm. 1 hit.
[Graphical view]

SUPFAM

SSF47240. Ferritin/RR_like. 1 hit.

PROSITE

PS00368. RIBORED_SMALL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P49723.

NextBio

973076.

Entry information

Entry name

RIR4_YEAST

Accession

Primary (citable) accession number: P49723
Secondary accession number(s): D6VUW4, Q66R92

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 137 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program