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Protein

Ribonucleoside-diphosphate reductase subunit M2

Gene

RRM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

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

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

DNA replication

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS10398-MONOMER.
ZFISH:HS10398-MONOMER.
BRENDAi1.17.4.1. 2681.
ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.
R-HSA-69205. G1/S-Specific Transcription.
SIGNORiP31350.
UniPathwayiUPA00326.

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

HGNCiHGNC:10452. RRM2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
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 residuei20PhosphoserineCombined sources1
Modified residuei33PhosphothreonineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP31350.
MaxQBiP31350.
PaxDbiP31350.
PeptideAtlasiP31350.
PRIDEiP31350.

PTM databases

iPTMnetiP31350.
PhosphoSitePlusiP31350.

Miscellaneous databases

PMAP-CutDBP31350.

Expressioni

Gene expression databases

BgeeiENSG00000171848.
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

WithEntry#Exp.IntActNotes
CCNFP4100212EBI-2339245,EBI-1207574
FZR1Q9UM112EBI-2339245,EBI-724997
RRM1P239213EBI-2339245,EBI-717006

Protein-protein interaction databases

BioGridi112155. 42 interactors.
DIPiDIP-24232N.
IntActiP31350. 21 interactors.
STRINGi9606.ENSP00000353770.

Chemistry databases

BindingDBiP31350.

Structurei

Secondary structure

1389
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni71 – 73Combined sources3
Turni77 – 80Combined sources4
Helixi88 – 99Combined sources12
Helixi104 – 106Combined sources3
Helixi110 – 112Combined sources3
Helixi113 – 118Combined sources6
Helixi121 – 147Combined sources27
Helixi149 – 152Combined sources4
Helixi156 – 183Combined sources28
Helixi187 – 194Combined sources8
Helixi196 – 199Combined sources4
Helixi201 – 203Combined sources3
Helixi204 – 215Combined sources12
Beta strandi217 – 219Combined sources3
Helixi221 – 233Combined sources13
Turni234 – 236Combined sources3
Helixi237 – 248Combined sources12
Helixi253 – 278Combined sources26
Helixi286 – 305Combined sources20
Helixi310 – 313Combined sources4
Helixi317 – 335Combined sources19

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...

Miscellaneous databases

EvolutionaryTraceiP31350.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

CDDicd01049. RNRR2. 1 hit.
Gene3Di1.10.620.20. 1 hit.
InterProiIPR009078. Ferritin-like_SF.
IPR012348. RNR-rel.
IPR033909. RNR_small.
IPR030475. RNR_small_AS.
IPR000358. RNR_small_fam.
[Graphical view]
PANTHERiPTHR23409. PTHR23409. 1 hit.
PfamiPF00268. Ribonuc_red_sm. 1 hit.
[Graphical view]
SUPFAMiSSF47240. SSF47240. 1 hit.
PROSITEiPS00368. RIBORED_SMALL. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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]
GeneIDi6241.
KEGGihsa:6241.
UCSCiuc021vdr.3. human. [P31350-1]

Keywords - Coding sequence diversityi

Alternative splicing

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. 42 interactors.
DIPiDIP-24232N.
IntActiP31350. 21 interactors.
STRINGi9606.ENSP00000353770.

Chemistry databases

BindingDBiP31350.
ChEMBLiCHEMBL1954.
DrugBankiDB00242. Cladribine.
DB05260. Gallium nitrate.
GuidetoPHARMACOLOGYi2631.

PTM databases

iPTMnetiP31350.
PhosphoSitePlusiP31350.

Polymorphism and mutation databases

BioMutaiRRM2.
DMDMi400979.

Proteomic databases

EPDiP31350.
MaxQBiP31350.
PaxDbiP31350.
PeptideAtlasiP31350.
PRIDEiP31350.

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]
GeneIDi6241.
KEGGihsa:6241.
UCSCiuc021vdr.3. human. [P31350-1]

Organism-specific databases

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

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00326.
BioCyciMetaCyc:HS10398-MONOMER.
ZFISH:HS10398-MONOMER.
BRENDAi1.17.4.1. 2681.
ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.
R-HSA-69205. G1/S-Specific Transcription.
SIGNORiP31350.

Miscellaneous databases

ChiTaRSiRRM2. human.
EvolutionaryTraceiP31350.
GeneWikiiRRM2.
GenomeRNAii6241.
PMAP-CutDBP31350.
PROiP31350.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171848.
CleanExiHS_RRM2.
ExpressionAtlasiP31350. baseline and differential.
GenevisibleiP31350. HS.

Family and domain databases

CDDicd01049. RNRR2. 1 hit.
Gene3Di1.10.620.20. 1 hit.
InterProiIPR009078. Ferritin-like_SF.
IPR012348. RNR-rel.
IPR033909. RNR_small.
IPR030475. RNR_small_AS.
IPR000358. RNR_small_fam.
[Graphical view]
PANTHERiPTHR23409. PTHR23409. 1 hit.
PfamiPF00268. Ribonuc_red_sm. 1 hit.
[Graphical view]
SUPFAMiSSF47240. SSF47240. 1 hit.
PROSITEiPS00368. RIBORED_SMALL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRIR2_HUMAN
AccessioniPrimary (citable) accession number: P31350
Secondary accession number(s): B2R9B5, J3KP43, Q5WRU7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 30, 2016
This is version 178 of the entry and version 1 of the sequence. [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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.