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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

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

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
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

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
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

Show more details

GO - Molecular functioni

  • disordered domain specific binding Source: Ensembl
  • identical protein binding Source: IntAct

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, 22 interactors
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
Turni6 – 8Combined sources3
Beta strandi10 – 12Combined sources3
Helixi15 – 23Combined sources9
Helixi24 – 26Combined sources3
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 strandi615 – 618Combined sources4
Beta strandi623 – 629Combined sources7
Beta strandi632 – 637Combined sources6
Helixi639 – 648Combined sources10
Helixi655 – 661Combined sources7
Turni662 – 664Combined sources3
Helixi666 – 668Combined sources3
Beta strandi670 – 672Combined sources3
Helixi674 – 679Combined sources6
Turni683 – 685Combined sources3
Helixi688 – 699Combined sources12
Beta strandi709 – 711Combined sources3
Helixi717 – 729Combined sources13
Beta strandi733 – 737Combined sources5

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

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 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

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: July 18, 2018
This is version 189 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. 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

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