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Protein

Ribonucleoside-diphosphate reductase large subunit

Gene

RRM1

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.

Catalytic activityi

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

Enzyme 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

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

DNA replication

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS09541-MONOMER.
ZFISH:HS09541-MONOMER.
BRENDAi1.17.4.1. 2681.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.
UniPathwayiUPA00326.

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

HGNCiHGNC:10451. RRM1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
DB00441. Gemcitabine.
DB01005. Hydroxyurea.
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.

PTM databases

iPTMnetiP23921.
PhosphoSitePlusiP23921.
SwissPalmiP23921.

Expressioni

Gene expression databases

BgeeiENSG00000167325.
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

WithEntry#Exp.IntActNotes
RRM2P313503EBI-717006,EBI-2339245

Protein-protein interaction databases

BioGridi112154. 37 interactors.
DIPiDIP-24233N.
IntActiP23921. 12 interactors.
MINTiMINT-1406473.
STRINGi9606.ENSP00000300738.

Chemistry databases

BindingDBiP23921.

Structurei

Secondary structure

1792
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 4Combined sources3
Beta strandi10 – 12Combined sources3
Helixi15 – 23Combined sources9
Turni31 – 33Combined sources3
Helixi36 – 44Combined sources9
Beta strandi48 – 50Combined sources3
Helixi53 – 66Combined sources14
Helixi67 – 69Combined sources3
Helixi78 – 88Combined sources11
Helixi94 – 103Combined sources10
Turni107 – 109Combined sources3
Helixi118 – 126Combined sources9
Helixi128 – 133Combined sources6
Helixi137 – 142Combined sources6
Helixi145 – 154Combined sources10
Beta strandi158 – 163Combined sources6
Helixi167 – 179Combined sources13
Helixi183 – 195Combined sources13
Beta strandi197 – 200Combined sources4
Helixi202 – 207Combined sources6
Beta strandi210 – 212Combined sources3
Beta strandi218 – 222Combined sources5
Helixi228 – 243Combined sources16
Beta strandi247 – 251Combined sources5
Beta strandi258 – 261Combined sources4
Helixi263 – 265Combined sources3
Beta strandi268 – 270Combined sources3
Helixi272 – 285Combined sources14
Beta strandi287 – 293Combined sources7
Beta strandi297 – 301Combined sources5
Helixi308 – 311Combined sources4
Turni312 – 315Combined sources4
Beta strandi317 – 319Combined sources3
Helixi321 – 323Combined sources3
Beta strandi328 – 334Combined sources7
Helixi336 – 343Combined sources8
Beta strandi347 – 351Combined sources5
Turni353 – 355Combined sources3
Helixi359 – 361Combined sources3
Helixi365 – 376Combined sources12
Beta strandi381 – 385Combined sources5
Helixi386 – 400Combined sources15
Beta strandi404 – 407Combined sources4
Helixi408 – 413Combined sources6
Helixi418 – 420Combined sources3
Beta strandi428 – 430Combined sources3
Beta strandi442 – 444Combined sources3
Beta strandi446 – 450Combined sources5
Helixi451 – 454Combined sources4
Beta strandi459 – 461Combined sources3
Helixi463 – 483Combined sources21
Helixi489 – 498Combined sources10
Beta strandi502 – 506Combined sources5
Helixi508 – 514Combined sources7
Beta strandi519 – 521Combined sources3
Helixi522 – 550Combined sources29
Helixi554 – 556Combined sources3
Helixi561 – 563Combined sources3
Helixi567 – 570Combined sources4
Beta strandi577 – 579Combined sources3
Helixi581 – 591Combined sources11
Helixi607 – 611Combined sources5
Beta strandi623 – 629Combined sources7
Beta strandi632 – 637Combined sources6
Helixi639 – 648Combined sources10
Helixi655 – 661Combined sources7
Turni662 – 664Combined sources3
Beta strandi670 – 672Combined sources3
Helixi674 – 679Combined sources6
Turni683 – 685Combined sources3
Helixi688 – 699Combined sources12
Helixi717 – 729Combined sources13
Beta strandi733 – 737Combined sources5

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[»]
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

Contains 1 ATP-cone domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1112. Eukaryota.
COG0209. LUCA.
GeneTreeiENSGT00390000001372.
HOGENOMiHOG000057035.
HOVERGENiHBG003447.
InParanoidiP23921.
KOiK10807.
OMAiKMTEIPD.
OrthoDBiEOG091G01XV.
PhylomeDBiP23921.
TreeFamiTF300578.

Family and domain databases

InterProiIPR005144. ATP-cone_dom.
IPR013346. NrdE_NrdA.
IPR000788. RNR_lg_C.
IPR013509. RNR_lsu_N.
IPR008926. RNR_R1-su_N.
[Graphical view]
PfamiPF03477. ATP-cone. 1 hit.
PF02867. Ribonuc_red_lgC. 1 hit.
PF00317. Ribonuc_red_lgN. 1 hit.
[Graphical view]
PRINTSiPR01183. RIBORDTASEM1.
SUPFAMiSSF48168. SSF48168. 1 hit.
TIGRFAMsiTIGR02506. NrdE_NrdA. 1 hit.
PROSITEiPS51161. ATP_CONE. 1 hit.
PS00089. RIBORED_LARGE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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 rs2228123dbSNPEnsembl.1
Natural variantiVAR_052053778V → A.Corresponds to variant rs2229196dbSNPEnsembl.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

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[»]
ProteinModelPortaliP23921.
SMRiP23921.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112154. 37 interactors.
DIPiDIP-24233N.
IntActiP23921. 12 interactors.
MINTiMINT-1406473.
STRINGi9606.ENSP00000300738.

Chemistry databases

BindingDBiP23921.
ChEMBLiCHEMBL1830.
DrugBankiDB00242. Cladribine.
DB00631. Clofarabine.
DB01073. Fludarabine.
DB00441. Gemcitabine.
DB01005. Hydroxyurea.
GuidetoPHARMACOLOGYi2630.

PTM databases

iPTMnetiP23921.
PhosphoSitePlusiP23921.
SwissPalmiP23921.

Polymorphism and mutation databases

BioMutaiRRM1.
DMDMi132608.

Proteomic databases

EPDiP23921.
MaxQBiP23921.
PaxDbiP23921.
PeptideAtlasiP23921.
PRIDEiP23921.

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.
GeneCardsiRRM1.
HGNCiHGNC:10451. RRM1.
HPAiCAB022093.
HPA057265.
HPA064297.
MIMi180410. gene.
neXtProtiNX_P23921.
OpenTargetsiENSG00000167325.
PharmGKBiPA298.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1112. Eukaryota.
COG0209. LUCA.
GeneTreeiENSGT00390000001372.
HOGENOMiHOG000057035.
HOVERGENiHBG003447.
InParanoidiP23921.
KOiK10807.
OMAiKMTEIPD.
OrthoDBiEOG091G01XV.
PhylomeDBiP23921.
TreeFamiTF300578.

Enzyme and pathway databases

UniPathwayiUPA00326.
BioCyciMetaCyc:HS09541-MONOMER.
ZFISH:HS09541-MONOMER.
BRENDAi1.17.4.1. 2681.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.

Miscellaneous databases

ChiTaRSiRRM1. human.
EvolutionaryTraceiP23921.
GeneWikiiRRM1.
GenomeRNAii6240.
PROiP23921.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167325.
CleanExiHS_RRM1.
ExpressionAtlasiP23921. baseline and differential.
GenevisibleiP23921. HS.

Family and domain databases

InterProiIPR005144. ATP-cone_dom.
IPR013346. NrdE_NrdA.
IPR000788. RNR_lg_C.
IPR013509. RNR_lsu_N.
IPR008926. RNR_R1-su_N.
[Graphical view]
PfamiPF03477. ATP-cone. 1 hit.
PF02867. Ribonuc_red_lgC. 1 hit.
PF00317. Ribonuc_red_lgN. 1 hit.
[Graphical view]
PRINTSiPR01183. RIBORDTASEM1.
SUPFAMiSSF48168. SSF48168. 1 hit.
TIGRFAMsiTIGR02506. NrdE_NrdA. 1 hit.
PROSITEiPS51161. ATP_CONE. 1 hit.
PS00089. RIBORED_LARGE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRIR1_HUMAN
AccessioniPrimary (citable) accession number: P23921
Secondary accession number(s): Q9UNN2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: November 2, 2016
This is version 176 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.
The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.