Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ribonucleoside-diphosphate reductase large subunit

Gene

RRM1

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.

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.
The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.

Catalytic activityi

2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.1 Publication

Activity regulationi

Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 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, the dATP inhibition is mediated by AHCYL1 which stabilizes dATP in the site.3 Publications

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
Binding sitei5Allosteric activatorBy similarity1
Binding sitei53Allosteric activatorBy similarity1
Binding sitei88Allosteric activatorBy similarity1
Binding sitei202SubstrateBy similarity1
Sitei218Important for hydrogen atom transferBy similarity1
Sitei226Allosteric effector binding, determines substrate specificity1
Binding sitei247Substrate; via amide nitrogenBy similarity1
Sitei256Allosteric effector binding, determines substrate specificity1
Active sitei427Proton acceptorBy similarity1
Active sitei429Cysteine radical intermediateBy similarity1
Active sitei431Proton acceptorBy similarity1
Sitei444Important for hydrogen atom transferBy similarity1
Sitei737Important for electron transferBy similarity1
Sitei738Important for electron transferBy similarity1
Sitei787Interacts with thioredoxin/glutaredoxinBy similarity1
Sitei790Interacts with thioredoxin/glutaredoxinBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Oxidoreductase
Biological processDNA replication
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS09541-MONOMER
BRENDAi1.17.4.1 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates
SIGNORiP23921
UniPathwayi
UPA00326

Names & Taxonomyi

Protein namesi
Recommended name:
Ribonucleoside-diphosphate reductase large subunit (EC:1.17.4.1)
Alternative name(s):
Ribonucleoside-diphosphate reductase subunit M1
Ribonucleotide reductase large subunit
Gene namesi
Name:RRM1
Synonyms:RR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000167325.14
HGNCiHGNC:10451 RRM1
MIMi180410 gene
neXtProtiNX_P23921

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
Mutagenesisi57D → N: Severely decreases interaction with AHCYL1 in the presence of dATP. 1 Publication1

Organism-specific databases

DisGeNETi6240
OpenTargetsiENSG00000167325
PharmGKBiPA298

Chemistry databases

ChEMBLiCHEMBL1830
DrugBankiDB00242 Cladribine
DB00631 Clofarabine
DB01073 Fludarabine
DB05420 gallium maltolate
DB00441 Gemcitabine
DB01005 Hydroxyurea
DB05003 Imexon
GuidetoPHARMACOLOGYi2630

Polymorphism and mutation databases

BioMutaiRRM1
DMDMi132608

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001871901 – 792Ribonucleoside-diphosphate reductase large subunitAdd BLAST792

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei17N6-acetyllysineCombined sources1
Disulfide bondi218 ↔ 444Redox-activeBy similarity
Modified residuei376N6-acetyllysineCombined sources1
Modified residuei751PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP23921
MaxQBiP23921
PaxDbiP23921
PeptideAtlasiP23921
PRIDEiP23921
ProteomicsDBi54166

PTM databases

iPTMnetiP23921
PhosphoSitePlusiP23921
SwissPalmiP23921

Expressioni

Gene expression databases

BgeeiENSG00000167325 Expressed in 244 organ(s), highest expression level in liver
CleanExiHS_RRM1
ExpressionAtlasiP23921 baseline and differential
GenevisibleiP23921 HS

Organism-specific databases

HPAiCAB022093
HPA057265
HPA064297

Interactioni

Subunit structurei

Heterodimer of a large and a small subunit. Heterodimer with small subunit RRM2 or RRM2B. The heterodimer with RRM2 has higher catalytic activity than the heterodimer with RRM2B. Interacts with AHCYL1 which inhibits its activity.3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112154, 38 interactors
ComplexPortaliCPX-2194 Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant
CPX-369 Ribonucleoside-diphosphate reductase RR1 complex, RRM2B variant
DIPiDIP-24233N
IntActiP23921, 14 interactors
STRINGi9606.ENSP00000300738

Chemistry databases

BindingDBiP23921

Structurei

Secondary structure

1792
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP23921
SMRiP23921
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23921

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 92ATP-conePROSITE-ProRule annotationAdd BLAST92

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 17Allosteric activator bindingBy similarity7
Regioni217 – 218Substrate bindingBy similarity2
Regioni285 – 288Allosteric effector binding, determines substrate specificity4
Regioni427 – 431Substrate bindingBy similarity5
Regioni603 – 607Substrate bindingBy similarity5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1112 Eukaryota
COG0209 LUCA
GeneTreeiENSGT00910000144246
HOGENOMiHOG000057035
HOVERGENiHBG003447
InParanoidiP23921
KOiK10807
OMAiDRYFLHI
OrthoDBiEOG091G01XV
PhylomeDBiP23921
TreeFamiTF300578

Family and domain databases

InterProiView protein in InterPro
IPR005144 ATP-cone_dom
IPR013346 NrdE_NrdA
IPR000788 RNR_lg_C
IPR013509 RNR_lsu_N
IPR008926 RNR_R1-su_N
PfamiView protein in Pfam
PF03477 ATP-cone, 1 hit
PF02867 Ribonuc_red_lgC, 1 hit
PF00317 Ribonuc_red_lgN, 1 hit
PRINTSiPR01183 RIBORDTASEM1
SUPFAMiSSF48168 SSF48168, 1 hit
TIGRFAMsiTIGR02506 NrdE_NrdA, 1 hit
PROSITEiView protein in PROSITE
PS51161 ATP_CONE, 1 hit
PS00089 RIBORED_LARGE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P23921-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MHVIKRDGRQ ERVMFDKITS RIQKLCYGLN MDFVDPAQIT MKVIQGLYSG
60 70 80 90 100
VTTVELDTLA AETAATLTTK HPDYAILAAR IAVSNLHKET KKVFSDVMED
110 120 130 140 150
LYNYINPHNG KHSPMVAKST LDIVLANKDR LNSAIIYDRD FSYNYFGFKT
160 170 180 190 200
LERSYLLKIN GKVAERPQHM LMRVSVGIHK EDIDAAIETY NLLSERWFTH
210 220 230 240 250
ASPTLFNAGT NRPQLSSCFL LSMKDDSIEG IYDTLKQCAL ISKSAGGIGV
260 270 280 290 300
AVSCIRATGS YIAGTNGNSN GLVPMLRVYN NTARYVDQGG NKRPGAFAIY
310 320 330 340 350
LEPWHLDIFE FLDLKKNTGK EEQRARDLFF ALWIPDLFMK RVETNQDWSL
360 370 380 390 400
MCPNECPGLD EVWGEEFEKL YASYEKQGRV RKVVKAQQLW YAIIESQTET
410 420 430 440 450
GTPYMLYKDS CNRKSNQQNL GTIKCSNLCT EIVEYTSKDE VAVCNLASLA
460 470 480 490 500
LNMYVTSEHT YDFKKLAEVT KVVVRNLNKI IDINYYPVPE ACLSNKRHRP
510 520 530 540 550
IGIGVQGLAD AFILMRYPFE SAEAQLLNKQ IFETIYYGAL EASCDLAKEQ
560 570 580 590 600
GPYETYEGSP VSKGILQYDM WNVTPTDLWD WKVLKEKIAK YGIRNSLLIA
610 620 630 640 650
PMPTASTAQI LGNNESIEPY TSNIYTRRVL SGEFQIVNPH LLKDLTERGL
660 670 680 690 700
WHEEMKNQII ACNGSIQSIP EIPDDLKQLY KTVWEISQKT VLKMAAERGA
710 720 730 740 750
FIDQSQSLNI HIAEPNYGKL TSMHFYGWKQ GLKTGMYYLR TRPAANPIQF
760 770 780 790
TLNKEKLKDK EKVSKEEEEK ERNTAAMVCS LENRDECLMC GS
Length:792
Mass (Da):90,070
Last modified:March 1, 1992 - v1
Checksum:i4470A76C61E8F86A
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YCY7H0YCY7_HUMAN
Ribonucleoside-diphosphate reductas...
RRM1
130Annotation score:
E9PL69E9PL69_HUMAN
Ribonucleoside-diphosphate reductas...
RRM1
570Annotation score:
E9PP77E9PP77_HUMAN
Ribonucleoside-diphosphate reductas...
RRM1
75Annotation score:
E9PRY9E9PRY9_HUMAN
Ribonucleoside-diphosphate reductas...
RRM1
37Annotation score:
E9PJ62E9PJ62_HUMAN
Ribonucleoside-diphosphate reductas...
RRM1
69Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6R → Q in AAD37491 (PubMed:9933563).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052052590K → Q. Corresponds to variant dbSNP:rs2228123Ensembl.1
Natural variantiVAR_052053778V → A. Corresponds to variant dbSNP:rs2229196Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59543 mRNA Translation: CAA42118.1
X59617 mRNA Translation: CAA42180.1
AF107045 Genomic DNA Translation: AAD37491.1
BC006498 mRNA Translation: AAH06498.1
L10342 Genomic DNA No translation available.
CCDSiCCDS7750.1
PIRiS16680
RefSeqiNP_001024.1, NM_001033.4
NP_001304993.1, NM_001318064.1
NP_001304994.1, NM_001318065.1
UniGeneiHs.445705

Genome annotation databases

EnsembliENST00000300738; ENSP00000300738; ENSG00000167325
GeneIDi6240
KEGGihsa:6240
UCSCiuc001lyw.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Ribonucleotide reductase entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59543 mRNA Translation: CAA42118.1
X59617 mRNA Translation: CAA42180.1
AF107045 Genomic DNA Translation: AAD37491.1
BC006498 mRNA Translation: AAH06498.1
L10342 Genomic DNA No translation available.
CCDSiCCDS7750.1
PIRiS16680
RefSeqiNP_001024.1, NM_001033.4
NP_001304993.1, NM_001318064.1
NP_001304994.1, NM_001318065.1
UniGeneiHs.445705

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WGHX-ray2.30A/B75-742[»]
3HNCX-ray2.41A/B1-792[»]
3HNDX-ray3.21A/B1-792[»]
3HNEX-ray3.11A/B1-792[»]
3HNFX-ray3.16A/B1-792[»]
4X3VX-ray3.70A/B1-792[»]
5D1YX-ray9.01A/B1-792[»]
5TUSX-ray2.66A/B1-792[»]
6AUIelectron microscopy3.30A/B/C/D/E/F1-792[»]
ProteinModelPortaliP23921
SMRiP23921
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112154, 38 interactors
ComplexPortaliCPX-2194 Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant
CPX-369 Ribonucleoside-diphosphate reductase RR1 complex, RRM2B variant
DIPiDIP-24233N
IntActiP23921, 14 interactors
STRINGi9606.ENSP00000300738

Chemistry databases

BindingDBiP23921
ChEMBLiCHEMBL1830
DrugBankiDB00242 Cladribine
DB00631 Clofarabine
DB01073 Fludarabine
DB05420 gallium maltolate
DB00441 Gemcitabine
DB01005 Hydroxyurea
DB05003 Imexon
GuidetoPHARMACOLOGYi2630

PTM databases

iPTMnetiP23921
PhosphoSitePlusiP23921
SwissPalmiP23921

Polymorphism and mutation databases

BioMutaiRRM1
DMDMi132608

Proteomic databases

EPDiP23921
MaxQBiP23921
PaxDbiP23921
PeptideAtlasiP23921
PRIDEiP23921
ProteomicsDBi54166

Protocols and materials databases

DNASUi6240
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300738; ENSP00000300738; ENSG00000167325
GeneIDi6240
KEGGihsa:6240
UCSCiuc001lyw.5 human

Organism-specific databases

CTDi6240
DisGeNETi6240
EuPathDBiHostDB:ENSG00000167325.14
GeneCardsiRRM1
HGNCiHGNC:10451 RRM1
HPAiCAB022093
HPA057265
HPA064297
MIMi180410 gene
neXtProtiNX_P23921
OpenTargetsiENSG00000167325
PharmGKBiPA298
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1112 Eukaryota
COG0209 LUCA
GeneTreeiENSGT00910000144246
HOGENOMiHOG000057035
HOVERGENiHBG003447
InParanoidiP23921
KOiK10807
OMAiDRYFLHI
OrthoDBiEOG091G01XV
PhylomeDBiP23921
TreeFamiTF300578

Enzyme and pathway databases

UniPathwayi
UPA00326

BioCyciMetaCyc:HS09541-MONOMER
BRENDAi1.17.4.1 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates
SIGNORiP23921

Miscellaneous databases

ChiTaRSiRRM1 human
EvolutionaryTraceiP23921
GeneWikiiRRM1
GenomeRNAii6240
PROiPR:P23921
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167325 Expressed in 244 organ(s), highest expression level in liver
CleanExiHS_RRM1
ExpressionAtlasiP23921 baseline and differential
GenevisibleiP23921 HS

Family and domain databases

InterProiView protein in InterPro
IPR005144 ATP-cone_dom
IPR013346 NrdE_NrdA
IPR000788 RNR_lg_C
IPR013509 RNR_lsu_N
IPR008926 RNR_R1-su_N
PfamiView protein in Pfam
PF03477 ATP-cone, 1 hit
PF02867 Ribonuc_red_lgC, 1 hit
PF00317 Ribonuc_red_lgN, 1 hit
PRINTSiPR01183 RIBORDTASEM1
SUPFAMiSSF48168 SSF48168, 1 hit
TIGRFAMsiTIGR02506 NrdE_NrdA, 1 hit
PROSITEiView protein in PROSITE
PS51161 ATP_CONE, 1 hit
PS00089 RIBORED_LARGE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRIR1_HUMAN
AccessioniPrimary (citable) accession number: P23921
Secondary accession number(s): Q9UNN2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: September 12, 2018
This is version 190 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

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again