The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity.
Protein arginine methylation is a prevalent posttranslational modification in eukaryotic cells that has been implicated in signal transduction, the metabolism of nascent pre-RNA, and the transcriptional activation processes. In searching the human genome for protein arginine N-methyltransferase (PRMT) family members, a novel gene has been found on chromosome 1 that encodes for an apparent methyltransferase, PRMT6. The polypeptide chain of PRMT6 is 41.9 kDa consisting of a catalytic core sequence common to other PRMT enzymes. Expressed as a glutathione S-transferase fusion protein, PRMT6 demonstrates type I PRMT activity, capable of forming both omega-N(G)-monomethylarginine and asymmetric omega-N(G),N(G)-dimethylarginine derivatives on the recombinant glycine- and arginine-rich substrate in a processive manner with a specific activity of 144 pmol methyl groups transferred min(-1) mg(-1) enzyme. A comparison of substrate specificity reveals that PRMT6 is functionally distinct from two previously characterized type I enzymes, PRMT1 and PRMT4. In addition, PRMT6 displays automethylation activity; it is the first PRMT to do so. This novel human PRMT, which resides solely in the nucleus when fused to the green fluorescent protein, joins a family of enzymes with diverse functions within cells.
Pubmed ID: 11724789 RIS Download
Amino Acid Sequence | Blotting, Northern | Catalytic Domain | Cell Nucleus | Chromosome Mapping | Chromosomes, Human, Pair 1 | Genome, Human | Glutathione Transferase | Humans | Isoenzymes | Kinetics | Molecular Sequence Data | Nuclear Proteins | Organ Specificity | Protein Processing, Post-Translational | Protein-Arginine N-Methyltransferases | Recombinant Fusion Proteins | Sequence Alignment | Sequence Homology, Amino Acid | Substrate Specificity | Transcriptional Activation