Ribonucleoside-Diphosphate Reductase Large Subunit (RRM1) Human Recombinant Protein

This gene encodes the large and catalytic subunit of ribonucleotide reductase, an enzyme essential for the conversion of ribonucleotides into deoxyribonucleotides. A pool of available deoxyribonucleotides is important for DNA replication during S phase of the cell cycle as well as multiple DNA repair processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

RRM1: an enzyme involved in DNA replication that provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Belongs to the ribonucleoside diphosphate reductase large chain family. Heterodimer of a large and a small subunit. Heterodimer with small subunit RRM2 or RRM2B. The heterodimer with RRM2 has higher catalytic activity than the heterodimer with RRM2B. 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. 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. Patients with advanced non-small cell lung cancer responded favorably to gemcitabine.

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

Chromosomal Location of Human Ortholog: 11p15.5

Cellular Component: cell projection; cell soma; cytoplasm; cytosol; nuclear envelope; nucleoplasm; ribonucleoside-diphosphate reductase complex

Molecular Function: ATP binding; protein binding; ribonucleoside-diphosphate reductase activity

Biological Process: cell proliferation in forebrain; deoxyribonucleotide biosynthetic process; DNA replication; male gonad development; mitotic cell cycle; nucleobase, nucleoside and nucleotide interconversion; nucleobase, nucleoside and nucleotide metabolic process; protein heterotetramerization; pyrimidine base metabolic process; response to ionizing radiation; retina development in camera-type eye