Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.17.4.1

Official Name

ribonucleoside-diphosphate reductase

Name from literature

ribonucleotide reductase

Pathway from literature

deoxyribonucleotide synthesis

Pathway from KEGG

Metabolism of Other Amino Acids; Glutathione metabolism; map00480

Cellular Processes; Cell Growth and Death; p53 signaling pathway; map04115

Nucleotide Metabolism; Purine metabolism; map00230

Nucleotide Metabolism; Pyrimidine metabolism; map00240

Organisms

Human (9606)

Genome localization

8q23.1[50484 ], 2p25-p24[6241 ], 11p15.5[6240 ],

Comments

This enzyme is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. An iron protein. While the enzyme is activated by ATP, it is inhibited by dATP [3,6].

Rate-limiting Description

"Ribonucleotide reductase (RR) is the enzyme that catalyses the rate-limiting step in DNA synthesis, the production of deoxynucleotides." (16925573)

"Ribonucleotide reductase is the rate-limiting enzyme for the de novo synthesis of deoxynucleoside triphosphates and therefore represents a good target for cancer chemotherapy." (12147300)

"This gene encodes the large subunit (M1) of ribonucleotide reductase, the heterodimeric enzyme that catalyzes the rate-limiting step in deoxyribonucleotide synthesis." (10441745)

"Recently, gemcitabine resistance has been associated with the up-regulation of mRNA and protein levels of the ribonucleotide reductase M2 subunit (RR-M2), a rate-limiting enzyme in DNA synthesis that is cell cycle regulated." (11489836)

"Ribonucleotide reductase (EC1.17.4.1; RR) catalyzes the rate-limiting step in DNA synthesis and plays a critical role in maintaining crucial substrates for DNA repair." (15571292)

Regulatory Information

Upstream transcription factor

7709;7157;4609

Regulatory type

Detail

key enzyme;

"(E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of ribonucleoside diphosphate reductase, a key enzyme in the de novo pathway of DNA synthesis." (10537300)

phosphorylation;

"Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction." (17693683)

transcriptional level;

"Human ribonucleotide reductase M2 subunit gene amplification and transcriptional regulation in a homogeneous staining chromosome region responsible for the mechanism of drug resistance" (11978967)

transcriptional level;

"Sequences downstream of the transcription initiation site are important for proper initiation and regulation of this gene's transcription." (12694192)

phosphorylation;

P23921

phosphorylation;

P31350

phosphorylation;

P31350:from_uniprot:20_Phosphoserine

transcriptional factor;TP53(7157)

"Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits." (12615712)

transcriptional factor;MYC(4609)

"Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes." (15856024)

transcriptional factor;ZBTB17(7709)

"Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes." (15856024)

transcriptional factor;TP53(7157)

"Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits." (12615712)

transcriptional factor;TP53(7157)

"Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits." (12615712#16189514)

Gene ontology

Gene ontology

GO:0004748 (F) ribonucleoside-diphosphate reductase activity [P31350, P23921, Q7LG56, Q53GZ5 ];
GO:0005737 (C) cytoplasm [Q7LG56 ];
GO:0005829 (C) cytosol [P31350, P23921 ];
GO:0005506 (F) iron ion binding [P31350, P23921, Q7LG56 ];
GO:0009186 (P) deoxyribonucleoside diphosphate metabolic p... [P31350, Q7LG56 ];
GO:0005524 (F) ATP binding [P23921 ];
GO:0006281 (P) DNA repair [Q7LG56 ];
GO:0005634 (C) nucleus [Q7LG56 ];
GO:0005971 (C) ribonucleoside-diphosphate reductase complex [P23921, Q53GZ5 ];
GO:0006260 (P) DNA replication [P31350, P23921, Q7LG56, Q53GZ5 ];
GO:0005515 (F) protein binding [P23921, Q53GZ5 ];
GO:0055114 (P) oxidation reduction [P31350, P23921, Q7LG56, Q53GZ5 ];

Tissue expression

Tissue From HPRD

Small intestine [01587 ];
Colon [01587 ];
Kidney [01587 ];
Heart [01587 ];
Leukocyte [01587 ];
Lung [01587 ];
Testis [01587 ];
Pancreas [01587 ];
Ovary [01587 ];
Skeletal muscle [01587 ];
Liver [01587 ];
Placenta [01587 ];
Lymphocyte [01588 ];
Brain [01587 ];
Mammary epithelium [01587 ];

Tissue specificity

Widely expressed with a high level in skeletal muscle and a weak level in thymus. Expressed in epithelial dysplasias and squamous cell carcinoma [Q7LG56 ];

Subcellular localization

Localization

nucleus [Q7LG56 ];

cytoplasm [P31350, P23921, Q7LG56 ];

Disease relevance

Disease

Ribonucleotide reductase is thought to mediate the pathogenesis of the immunodeficiency of adenosine deaminase or purine nucleoside phosphorylase. The deoxynucleotides that accumulate in the lymphoid cells of these patients are thought to feed-back inhibit ribonucleotide reductase, preventing DNA replication and cell proliferation [P31350, P23921 ];

Defects in RRM2B are the cause of encephalomyopathic mitochondrial depletion syndrome with renal tubulopathy (EMDSRT) [MIM:612075]. Mitochondrial DNA depletion syndrome (MDS) is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA (mtDNA) copy number. The encephalomyopathic form with renal tubulopathy is presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis [Q7LG56 ];

Links

SwissProt

B3KS26; B4E2N4; P23921; P31350; Q53GZ5; Q7LG56

Entrez Gene

50484; 6240; 6241

HPRD

01587; 05276; 01588



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  Last Modified: 2009-03-24  
  Design by Zhao Min