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.
Frankel
Adam
A
University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, Texas 78957, USA.
Yadav
Neelu
N
Lee
Jaeho
J
Branscombe
Tina L
TL
Clarke
Steven
S
Bedford
Mark T
MT
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D020134:Catalytic Domain; D002467:Cell Nucleus / Q000201:enzymology*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D015894:Genome, Human; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D015533:Transcriptional Activation
D007527:Isoenzymes; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases; D005982:Glutathione Transferase