P07742 · RIR1_MOUSE
- ProteinRibonucleoside-diphosphate reductase large subunit
- GeneRrm1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids792 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 activity
- [thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-diphosphate
RHEA-COMP:10700 CHEBI:50058 Position: n/n+3+ CHEBI:73316 + CHEBI:15377 = RHEA-COMP:10698 CHEBI:29950 Position: nCHEBI:29950 Position: n+3+ CHEBI:57930
Activity regulation
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 (By similarity).
Features
Showing features for binding site, site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 5-6 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: KR | ||||||
Binding site | 11-17 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: ERVMFDK | ||||||
Binding site | 53 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: T | ||||||
Binding site | 57 | ATP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: D | ||||||
Binding site | 202 | GDP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 217 | GDP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Site | 218 | Important for hydrogen atom transfer | ||||
Sequence: C | ||||||
Binding site | 226-228 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: DSI | ||||||
Binding site | 243 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: K | ||||||
Binding site | 256 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: R | ||||||
Binding site | 263-264 | dTTP (UniProtKB | ChEBI); allosteric effector that controls substrate specificity | ||||
Sequence: AG | ||||||
Active site | 427 | Proton acceptor | ||||
Sequence: N | ||||||
Binding site | 427 | GDP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 429 | Cysteine radical intermediate | ||||
Sequence: C | ||||||
Active site | 431 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 431 | GDP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Site | 444 | Important for hydrogen atom transfer | ||||
Sequence: C | ||||||
Binding site | 604-607 | GDP (UniProtKB | ChEBI) | ||||
Sequence: TAST | ||||||
Site | 737 | Important for electron transfer | ||||
Sequence: Y | ||||||
Site | 738 | Important for electron transfer | ||||
Sequence: Y | ||||||
Site | 787 | Interacts with thioredoxin/glutaredoxin | ||||
Sequence: C | ||||||
Site | 790 | Interacts with thioredoxin/glutaredoxin | ||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRibonucleoside-diphosphate reductase large subunit
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP07742
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 39 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000187191 | 1-792 | Ribonucleoside-diphosphate reductase large subunit | |||
Sequence: MHVIKRDGRQERVMFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSGVTTVELDTLAAETAATLTTKHPDYAILAARIAVSNLHKETKKVFSDVMEDLYNYINPHNGRHSPMVASSTLDIVMANKDRLNSAIIYDRDFSYNYFGFKTLERSYLLKINGKVAERPQHMLMRVSVGIHKEDIDAAIETYNLLSEKWFTHASPTLFNAGTNRPQLSSCFLLSMKDDSIEGIYDTLKQCALISKSAGGIGVAVSCIRATGSYIAGTNGNSNGLVPMLRVYNNTARYVDQGGNKRPGAFAIYLEPWHLDIFEFLDLKKNTGKEEQRARDLFFALWIPDLFMKRVETNQDWSLMCPNECPGLDEVWGEEFEKLYESYEKQGRVRKVVKAQQLWYAIIESQTETGTPYMLYKDSCNRKSNQQNLGTIKCSNLCTEIVEYTSKDEVAVCNLASLALNMYVTPEHTYDFEKLAEVTKVIVRNLNKIIDINYYPIPEAHLSNKRHRPIGIGVQGLADAFILMRYPFESPEAQLLNKQIFETIYYGALEASCELAKEYGPYETYEGSPVSKGILQYDMWNVAPTDLWDWKPLKEKIAKYGIRNSLLIAPMPTASTAQILGNNESIEPYTSNIYTRRVLSGEFQIVNPHLLKDLTERGLWNEEMKNQIIACNGSIQSIPEIPDDLKQLYKTVWEISQKTVLKMAAERGAFIDQSQSLNIHIAEPNYGKLTSMHFYGWKQGLKTGMYYLRTRPAANPIQFTLNKEKLKDKEKALKEEEEKERNTAAMVCSLENREECLMCGS | ||||||
Modified residue | 17 | N6-acetyllysine | ||||
Sequence: K | ||||||
Disulfide bond | 218↔444 | Redox-active | ||||
Sequence: CFLLSMKDDSIEGIYDTLKQCALISKSAGGIGVAVSCIRATGSYIAGTNGNSNGLVPMLRVYNNTARYVDQGGNKRPGAFAIYLEPWHLDIFEFLDLKKNTGKEEQRARDLFFALWIPDLFMKRVETNQDWSLMCPNECPGLDEVWGEEFEKLYESYEKQGRVRKVVKAQQLWYAIIESQTETGTPYMLYKDSCNRKSNQQNLGTIKCSNLCTEIVEYTSKDEVAVC | ||||||
Modified residue | 376 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 751 | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Heterodimer of a large and a small subunit. Interacts with RRM2B. Interacts with AHCYL1 which inhibits its activity (By similarity).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-92 | ATP-cone | ||||
Sequence: MHVIKRDGRQERVMFDKITSRIQKLCYGLNMDFVDPAQITMKVIQGLYSGVTTVELDTLAAETAATLTTKHPDYAILAARIAVSNLHKETKK |
Sequence similarities
Belongs to the ribonucleoside diphosphate reductase large chain family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length792
- Mass (Da)90,210
- Last updated2011-07-27 v2
- Checksum051C6CE407D24C69
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1B0GSB1 | A0A1B0GSB1_MOUSE | Rrm1 | 65 | ||
A0A1B0GRW5 | A0A1B0GRW5_MOUSE | Rrm1 | 36 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 202 | in Ref. 1; AAA40061 | ||||
Sequence: S → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
K02927 EMBL· GenBank· DDBJ | AAA40061.1 EMBL· GenBank· DDBJ | mRNA | ||
AK088043 EMBL· GenBank· DDBJ | BAC40112.1 EMBL· GenBank· DDBJ | mRNA | ||
AK137075 EMBL· GenBank· DDBJ | BAE23230.1 EMBL· GenBank· DDBJ | mRNA | ||
AK168586 EMBL· GenBank· DDBJ | BAE40455.1 EMBL· GenBank· DDBJ | mRNA | ||
CH466531 EMBL· GenBank· DDBJ | EDL16602.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC016450 EMBL· GenBank· DDBJ | AAH16450.1 EMBL· GenBank· DDBJ | mRNA |