Cloning and Expression of a Novel Human Glutaredoxin (Grx2) with Mitochondrial and Nuclear Isoforms

摘要: Glutaredoxin (Grx) is a glutathione-dependent hydrogen donor for ribonucleotide reductase. Today glutaredoxins are known as multifunctional family of GSH-disulfide-oxidoreductases belonging to the thioredoxin fold superfamily. In contrast Escherichia coli and yeast, single human glutaredoxin known. We have identified cloned novel 18-kDa dithiol glutaredoxin, named glutaredoxin-2 (Grx2), which 34% identical previously cytosolic 12-kDa Grx1. The Grx2 sequence contains three characteristic regions family: dithiol/disulfide active site, CSYC, GSH binding hydrophobic surface area. gene, located at chromosome 1q31.2--31.3, consisted five exons that were transcribed 0.9-kilobase mRNA ubiquitously expressed in several tissues. Two alternatively spliced isoforms differed their 5' region identified. These corresponded alternative proteins with common 125-residue C-terminal Grx domain but different N-terminal extensions 39 40 residues, respectively. two full-length variants E. exhibited GSH-dependent hydroxyethyl disulfide dehydroascorbate reducing activities. Western blot analysis subcellular fractions from Jurkat cells specific anti-Grx2 antibody showed was predominantly nucleus also present mitochondria. further one corresponding Grx2a encoded functional mitochondrial translocation signal.