RRM2B Human Recombinant Protein

This gene encodes the small subunit of a p53-inducible ribonucleotide reductase. This heterotetrameric enzyme catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. The product of this reaction is necessary for DNA synthesis. Mutations in this gene have been associated with autosomal recessive mitochondrial DNA depletion syndrome, autosomal dominant progressive external ophthalmoplegia-5, and mitochondrial neurogastrointestinal encephalopathy. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

RRM2B: 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. Defects in RRM2B are the cause of mitochondrial DNA depletion syndrome type 8A (MTDPS8A). A disorder due to mitochondrial dysfunction characterized by various combinations of neonatal hypotonia, neurological deterioration, respiratory distress, lactic acidosis, and renal tubulopathy. Defects in RRM2B are the cause of mitochondrial DNA depletion syndrome type 8B (MTDPS8B). A disease due to mitochondrial dysfunction and characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy. Defects in RRM2B are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 5 (PEOA5). A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Belongs to the ribonucleoside diphosphate reductase small chain family. 5 isoforms of the human protein are produced by alternative splicing.

Protein type: Nucleotide Metabolism - purine; EC 1.17.4.1; Nucleotide Metabolism - pyrimidine; Oxidoreductase; Other Amino Acids Metabolism - glutathione

Chromosomal Location of Human Ortholog: 8q23.1

Cellular Component: nucleoplasm; cytoplasm

Molecular Function: metal ion binding; ribonucleoside-diphosphate reductase activity

Biological Process: deoxyribonucleoside diphosphate metabolic process; renal system process; nucleobase, nucleoside and nucleotide metabolic process; nucleobase, nucleoside and nucleotide interconversion; deoxyribonucleotide biosynthetic process; response to oxidative stress; mitochondrial DNA replication; kidney development; DNA repair; deoxyribonucleoside triphosphate metabolic process

Disease: Mitochondrial Dna Depletion Syndrome 8a (encephalomyopathic Type With Renal Tubulopathy); Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Dominant, 5