Ribonucleoside-diphosphate reductase large subunit

Function

Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.

Classification

Family (Pfam)

PF03477 ATP-cone, PF02867 Ribonuc_red_lgC, PF00317 Ribonuc_red_lgN

InterPro

ATP-cone_dom, NrdE_NrdA_C, RNR_lg_C, RNR_lsu_N, RNR_R1-su_N, Rrm1

Functional cluster

Central Metabolic Enzymes (KARI/Glycolysis)

Experimental structures · PDB · 12

• 2WGH X-ray 2.30A
• 3HNC X-ray 2.41A
• 3HND X-ray 3.21A
• 3HNE X-ray 3.11A
• 3HNF X-ray 3.16A
• 4X3V X-ray 3.70A
• 5D1Y X-ray 9.01A
• 5TUS X-ray 2.66A
• 6AUI EM 3.30A
• 6L3R X-ray 2.00A
• 6L7L X-ray 2.17A
• 6LKM X-ray 2.55A

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0005829 cytosol
• GO:0005739 mitochondrion
• GO:0005971 ribonucleoside-diphosphate reductase complex
• GO:0005524 ATP binding
• GO:0097718 disordered domain specific binding
• GO:0042802 identical protein binding
• GO:0061731 ribonucleoside-diphosphate reductase activity
• GO:0036175 ribonucleoside-diphosphate reductase activity, glutaredoxin disulfide as acceptor
• GO:0004748 ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
• GO:0009265 2'-deoxyribonucleotide biosynthetic process
• GO:0009263 deoxyribonucleotide biosynthetic process
• GO:0006281 DNA repair
• GO:0000731 DNA synthesis involved in DNA repair
• GO:0006264 mitochondrial DNA replication
• GO:0070318 positive regulation of G0 to G1 transition
• GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
• GO:0010971 positive regulation of G2/M transition of mitotic cell cycle
• GO:0051290 protein heterotetramerization
• GO:0009185 ribonucleoside diphosphate metabolic process

Disease associations

• progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6 MONDO:0957993

Drugs targeting this protein · 6

• FLUDARABINE PHOSPHATE inhibitor
• GEMCITABINE HYDROCHLORIDE inhibitor
• CLOFARABINE inhibitor
• TRIAPINE inhibitor
• TEZACITABINE inhibitor
• HYDROXYUREA inhibitor

Related proteins · sequence + function similarity

• Ribonucleoside-diphosphate reductase large subunit 1.00
• Ribonucleoside-diphosphate reductase large subunit 0.99
• Ribonucleoside-diphosphate reductase large subunit 0.99
• Ribonucleoside-diphosphate reductase large subunit 0.98
• Ribonucleoside-diphosphate reductase large subunit 0.98
• Ribonucleoside-diphosphate reductase large subunit 0.98
• Ribonucleoside-diphosphate reductase large subunit 0.97
• Ribonucleoside-diphosphate reductase large subunit 0.96
• Ribonucleoside-diphosphate reductase large chain 0.96
• Ribonucleoside-diphosphate reductase large subunit 0.95
• Ribonucleoside-diphosphate reductase large subunit 0.95
• Ribonucleoside-diphosphate reductase large chain 0.95

Co-cited proteins · studied together in the literature

• Ribonucleoside-diphosphate reductase subunit M2 B 2 shared papers
• Ribonucleoside-diphosphate reductase subunit M2 1 shared papers
• S-adenosylhomocysteine hydrolase-like protein 1 1 shared papers
• E3 ubiquitin-protein ligase TRIM21 1 shared papers

Literature · 14 cited papers

• RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. J. Clin. Invest. · 2022
• Enzyme regulation. IRBIT is a novel regulator of ribonucleotide reductase in higher eukaryotes. Science · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization. Nat. Struct. Mol. Biol. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
• Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits. Biochem. Biophys. Res. Commun. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits. Cancer Res. · 2003
• A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region. Genomics · 1999
• Human R1 subunit of ribonucleotide reductase (RRM1): 5' flanking region of the gene. Genomics · 1994
• Human ribonucleotide reductase. Activation and inhibition by analogs of ATP. Biochem. Pharmacol. · 1991
• … and 2 more in the literature graph