Protein arginine methylation is an important posttranslational modification in eukaryotic cells, which has been implicated in RNA processing and trafficking, receptor-mediated signaling, and transcription. PRMT6 was identified by searching the human genome for protein arginine N-methyltransferase (PRMT) family members. PRMT6 cDNA codes for a protein of approximate molecular weight of 42kD consisting of a catalytic core sequence common to other PRMT enzymes. PRMT6 demonstrates type I PRMT activity, capable of forming both >NG-monomethylarginine and asymmetric >NG,NG- dimethylarginine derivatives on the recombinant glycine- and arginine-rich substrates. A comparison of substrate specificity reveals that PRMT6 is functionally distinct from two previously characterized type I enzymes, PRMT1 and PRMT4. In addition to methylating substrate proteins, PRMT6 displays automethylation activit. GFP-fusion protein expression in the transfected cell lines suggest that PRMT6 localizes in the nucleus.