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Protein

Ribonucleoside-diphosphate reductase subunit M2

Gene

RRM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

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.

Catalytic activityi

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

Cofactori

Fe cationBy similarityNote: Binds 2 iron ions per subunit.By similarity

Pathwayi: DNA replication

This protein is involved in the pathway DNA replication, which is part of Genetic information processing.
View all proteins of this organism that are known to be involved in the pathway DNA replication and in Genetic information processing.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi138Iron 1PROSITE-ProRule annotation1
Metal bindingi169Iron 1PROSITE-ProRule annotation1
Metal bindingi169Iron 2By similarity1
Metal bindingi172Iron 1PROSITE-ProRule annotation1
Active sitei176PROSITE-ProRule annotation1
Metal bindingi232Iron 2By similarity1
Metal bindingi266Iron 2By similarity1
Metal bindingi269Iron 2By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processDNA replication
LigandIron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS10398-MONOMER
BRENDAi1.17.4.1 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-8953750 Transcriptional Regulation by E2F6
SIGNORiP31350
UniPathwayi
UPA00326

Names & Taxonomyi

Protein namesi
Recommended name:
Ribonucleoside-diphosphate reductase subunit M2 (EC:1.17.4.1)
Alternative name(s):
Ribonucleotide reductase small chain
Ribonucleotide reductase small subunit
Gene namesi
Name:RRM2
Synonyms:RR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000171848.13
HGNCiHGNC:10452 RRM2
MIMi180390 gene
neXtProtiNX_P31350

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20S → A: Enhances inhibitory effect on Wnt signaling. 1
Mutagenesisi20S → E: Prevents inhibitory effect on Wnt signaling. 1

Organism-specific databases

DisGeNETi6241
OpenTargetsiENSG00000171848
PharmGKBiPA299

Chemistry databases

ChEMBLiCHEMBL1954
DrugBankiDB00242 Cladribine
DB05260 Gallium nitrate
DB05801 GTI 2040
DB05003 Imexon
DB05428 motexafin gadolinium
GuidetoPHARMACOLOGYi2631

Polymorphism and mutation databases

BioMutaiRRM2
DMDMi400979

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001904471 – 389Ribonucleoside-diphosphate reductase subunit M2Add BLAST389

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei20PhosphoserineBy similarity1
Modified residuei33PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylation on Ser-20 relieves the inhibitory effect on Wnt signaling.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP31350
MaxQBiP31350
PaxDbiP31350
PeptideAtlasiP31350
PRIDEiP31350
ProteomicsDBi54784

PTM databases

iPTMnetiP31350
PhosphoSitePlusiP31350

Miscellaneous databases

PMAP-CutDBiP31350

Expressioni

Gene expression databases

BgeeiENSG00000171848 Expressed in 163 organ(s), highest expression level in secondary oocyte
CleanExiHS_RRM2
ExpressionAtlasiP31350 baseline and differential
GenevisibleiP31350 HS

Organism-specific databases

HPAiHPA056994

Interactioni

Subunit structurei

Heterodimer of a large and a small subunit.

Binary interactionsi

Protein-protein interaction databases

BioGridi112155, 56 interactors
ComplexPortaliCPX-2194 Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant
DIPiDIP-24232N
IntActiP31350, 24 interactors
STRINGi9606.ENSP00000353770

Chemistry databases

BindingDBiP31350

Structurei

Secondary structure

1389
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP31350
SMRiP31350
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31350

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1567 Eukaryota
COG0208 LUCA
GeneTreeiENSGT00390000013305
HOGENOMiHOG000255975
HOVERGENiHBG001647
InParanoidiP31350
KOiK10808
OMAiFYVGFVQ
OrthoDBiEOG091G0AZQ
PhylomeDBiP31350
TreeFamiTF300465

Family and domain databases

CDDicd01049 RNRR2, 1 hit
Gene3Di1.10.620.20, 1 hit
InterProiView protein in InterPro
IPR009078 Ferritin-like_SF
IPR012348 RNR-like
IPR033909 RNR_small
IPR030475 RNR_small_AS
IPR000358 RNR_small_fam
PANTHERiPTHR23409 PTHR23409, 1 hit
PfamiView protein in Pfam
PF00268 Ribonuc_red_sm, 1 hit
SUPFAMiSSF47240 SSF47240, 1 hit
PROSITEiView protein in PROSITE
PS00368 RIBORED_SMALL, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.iShow all

Isoform 1 (identifier: P31350-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLSLRVPLAP ITDPQQLQLS PLKGLSLVDK ENTPPALSGT RVLASKTARR
60 70 80 90 100
IFQEPTEPKT KAAAPGVEDE PLLRENPRRF VIFPIEYHDI WQMYKKAEAS
110 120 130 140 150
FWTAEEVDLS KDIQHWESLK PEERYFISHV LAFFAASDGI VNENLVERFS
160 170 180 190 200
QEVQITEARC FYGFQIAMEN IHSEMYSLLI DTYIKDPKER EFLFNAIETM
210 220 230 240 250
PCVKKKADWA LRWIGDKEAT YGERVVAFAA VEGIFFSGSF ASIFWLKKRG
260 270 280 290 300
LMPGLTFSNE LISRDEGLHC DFACLMFKHL VHKPSEERVR EIIINAVRIE
310 320 330 340 350
QEFLTEALPV KLIGMNCTLM KQYIEFVADR LMLELGFSKV FRVENPFDFM
360 370 380
ENISLEGKTN FFEKRVGEYQ RMGVMSSPTE NSFTLDADF
Length:389
Mass (Da):44,878
Last modified:July 1, 1993 - v1
Checksum:i10E6F5F84D34DA94
GO
Isoform 2 (identifier: P31350-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGRVGGMAQPMGRAGAPKPMGRAGSARRGRFKGCWSEGSPVHPVPAVLSWLLALLRCASTM

Note: No experimental confirmation available.Curated
Show »
Length:449
Mass (Da):51,093
Checksum:iDFEA2E41A26BD80E
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JXC1C9JXC1_HUMAN
Ribonucleoside-diphosphate reductas...
RRM2
289Annotation score:

Sequence cautioni

The sequence DA477511 differs from that shown. Reason: Frameshift at position 87.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 2 (identifier: P31350-2)
Sequence conflicti28R → H in DA477511 (PubMed:14702039).Curated1
Sequence conflicti59S → A in DA477511 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449171M → MGRVGGMAQPMGRAGAPKPM GRAGSARRGRFKGCWSEGSP VHPVPAVLSWLLALLRCAST M in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59618 mRNA Translation: CAA42181.1
S40301 mRNA Translation: AAA09577.1
AY032750 Genomic DNA Translation: AAK51163.1
AK313719 mRNA Translation: BAG36462.1
DA477511 mRNA No translation available.
AC104794 Genomic DNA Translation: AAX93099.1
AC118058 Genomic DNA No translation available.
BC001886 mRNA Translation: AAH01886.1
BC030154 mRNA Translation: AAH30154.1
CCDSiCCDS1669.1 [P31350-1]
CCDS54334.1 [P31350-2]
PIRiS25854
RefSeqiNP_001025.1, NM_001034.3 [P31350-1]
NP_001159403.1, NM_001165931.1 [P31350-2]
UniGeneiHs.226390

Genome annotation databases

EnsembliENST00000304567; ENSP00000302955; ENSG00000171848 [P31350-1]
ENST00000360566; ENSP00000353770; ENSG00000171848 [P31350-2]
ENST00000615152; ENSP00000484183; ENSG00000171848 [P31350-2]
ENST00000641198; ENSP00000493399; ENSG00000171848 [P31350-1]
GeneIDi6241
KEGGihsa:6241
UCSCiuc021vdr.3 human [P31350-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Ribonucleotide reductase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59618 mRNA Translation: CAA42181.1
S40301 mRNA Translation: AAA09577.1
AY032750 Genomic DNA Translation: AAK51163.1
AK313719 mRNA Translation: BAG36462.1
DA477511 mRNA No translation available.
AC104794 Genomic DNA Translation: AAX93099.1
AC118058 Genomic DNA No translation available.
BC001886 mRNA Translation: AAH01886.1
BC030154 mRNA Translation: AAH30154.1
CCDSiCCDS1669.1 [P31350-1]
CCDS54334.1 [P31350-2]
PIRiS25854
RefSeqiNP_001025.1, NM_001034.3 [P31350-1]
NP_001159403.1, NM_001165931.1 [P31350-2]
UniGeneiHs.226390

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2UW2X-ray2.80A60-389[»]
3OLJX-ray2.10A/B/C/D66-350[»]
3VPMX-ray2.70A/B66-350[»]
3VPNX-ray2.25A/B66-350[»]
3VPOX-ray2.30A/B66-350[»]
ProteinModelPortaliP31350
SMRiP31350
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112155, 56 interactors
ComplexPortaliCPX-2194 Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant
DIPiDIP-24232N
IntActiP31350, 24 interactors
STRINGi9606.ENSP00000353770

Chemistry databases

BindingDBiP31350
ChEMBLiCHEMBL1954
DrugBankiDB00242 Cladribine
DB05260 Gallium nitrate
DB05801 GTI 2040
DB05003 Imexon
DB05428 motexafin gadolinium
GuidetoPHARMACOLOGYi2631

PTM databases

iPTMnetiP31350
PhosphoSitePlusiP31350

Polymorphism and mutation databases

BioMutaiRRM2
DMDMi400979

Proteomic databases

EPDiP31350
MaxQBiP31350
PaxDbiP31350
PeptideAtlasiP31350
PRIDEiP31350
ProteomicsDBi54784

Protocols and materials databases

DNASUi6241
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000304567; ENSP00000302955; ENSG00000171848 [P31350-1]
ENST00000360566; ENSP00000353770; ENSG00000171848 [P31350-2]
ENST00000615152; ENSP00000484183; ENSG00000171848 [P31350-2]
ENST00000641198; ENSP00000493399; ENSG00000171848 [P31350-1]
GeneIDi6241
KEGGihsa:6241
UCSCiuc021vdr.3 human [P31350-1]

Organism-specific databases

CTDi6241
DisGeNETi6241
EuPathDBiHostDB:ENSG00000171848.13
GeneCardsiRRM2
HGNCiHGNC:10452 RRM2
HPAiHPA056994
MIMi180390 gene
neXtProtiNX_P31350
OpenTargetsiENSG00000171848
PharmGKBiPA299
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1567 Eukaryota
COG0208 LUCA
GeneTreeiENSGT00390000013305
HOGENOMiHOG000255975
HOVERGENiHBG001647
InParanoidiP31350
KOiK10808
OMAiFYVGFVQ
OrthoDBiEOG091G0AZQ
PhylomeDBiP31350
TreeFamiTF300465

Enzyme and pathway databases

UniPathwayi
UPA00326

BioCyciMetaCyc:HS10398-MONOMER
BRENDAi1.17.4.1 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-8953750 Transcriptional Regulation by E2F6
SIGNORiP31350

Miscellaneous databases

ChiTaRSiRRM2 human
EvolutionaryTraceiP31350
GeneWikiiRRM2
GenomeRNAii6241
PMAP-CutDBiP31350
PROiPR:P31350
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171848 Expressed in 163 organ(s), highest expression level in secondary oocyte
CleanExiHS_RRM2
ExpressionAtlasiP31350 baseline and differential
GenevisibleiP31350 HS

Family and domain databases

CDDicd01049 RNRR2, 1 hit
Gene3Di1.10.620.20, 1 hit
InterProiView protein in InterPro
IPR009078 Ferritin-like_SF
IPR012348 RNR-like
IPR033909 RNR_small
IPR030475 RNR_small_AS
IPR000358 RNR_small_fam
PANTHERiPTHR23409 PTHR23409, 1 hit
PfamiView protein in Pfam
PF00268 Ribonuc_red_sm, 1 hit
SUPFAMiSSF47240 SSF47240, 1 hit
PROSITEiView protein in PROSITE
PS00368 RIBORED_SMALL, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRIR2_HUMAN
AccessioniPrimary (citable) accession number: P31350
Secondary accession number(s): B2R9B5, J3KP43, Q5WRU7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: September 12, 2018
This is version 192 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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