Ribonucleoside-diphosphate reductase subunit M2 B

Function

Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage.

Classification

Family (Pfam)

PF00268 Ribonuc_red_sm

InterPro

Ferritin-like_SF, RNR-like, RNR_small, RNR_small_AS, RNR_small_fam

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 3

• 2VUX X-ray 2.80A
• 3HF1 X-ray 2.60A
• 4DJN X-ray 2.20A

A predicted model is available from AlphaFold.

Gene Ontology · 15

• GO:0005829 cytosol
• GO:0005739 mitochondrion
• GO:0005654 nucleoplasm
• GO:0042802 identical protein binding
• GO:0046872 metal ion binding
• 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:0010971 positive regulation of G2/M transition of mitotic cell cycle
• GO:0014075 response to amine
• GO:0009185 ribonucleoside diphosphate metabolic process

Disease associations

• rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction MONDO:0010000
• mitochondrial DNA depletion syndrome 8a MONDO:0012792
• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 MONDO:0013117

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 subunit M2 B 1.00
• Ribonucleoside-diphosphate reductase subunit M2 B 0.99
• Ribonucleoside-diphosphate reductase subunit M2 0.93
• Ribonucleoside-diphosphate reductase subunit M2 0.93
• Ribonucleoside-diphosphate reductase subunit M2 0.92
• Ribonucleoside-diphosphate reductase subunit M2 0.92
• Ribonucleoside-diphosphate reductase subunit M2 0.92
• Ribonucleoside-diphosphate reductase subunit M2 0.92
• Ribonucleoside-diphosphate reductase subunit M2 0.90
• Ribonucleoside-diphosphate reductase small chain 0.90
• Ribonucleoside-diphosphate reductase small chain 0.89
• Ribonucleoside-diphosphate reductase small chain 0.89

Co-cited proteins · studied together in the literature

• Ribonucleoside-diphosphate reductase subunit M2 B 1 shared papers
• Ribonucleoside-diphosphate reductase large subunit 2 shared papers
• Protoheme IX farnesyltransferase, mitochondrial 1 shared papers
• NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 1 shared papers
• Nondiscriminating glutamyl-tRNA synthetase EARS2, mitochondrial 1 shared papers
• Enoyl-CoA hydratase, mitochondrial 1 shared papers
• 5-taurinomethyluridine-[tRNA] synthase subunit GTPB3, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial 1 shared papers
• Small ribosomal subunit protein mS23 1 shared papers
• Glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial 1 shared papers
• Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial 1 shared papers

Literature · 18 cited papers

• Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B. Hum. Mutat. · 2020
• A comprehensive genomic analysis reveals the genetic landscape of mitochondrial respiratory chain complex deficiencies. PLoS Genet. · 2016
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• 2.6 A X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase. Biochemistry · 2009
• Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. Arch. Neurol. · 2009
• A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. Am. J. Hum. Genet. · 2009
• Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene. Neuromuscul. Disord. · 2008
• The full-ORF clone resource of the German cDNA consortium. BMC Genomics · 2007
• Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat. Genet. · 2007
• DNA sequence and analysis of human chromosome 8. Nature · 2006
• 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
• … and 6 more in the literature graph