protein arginine N-methyltransferase 6; heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 6; histone-arginine N-methyltransferase PRMT6 (PRMT6, HRMT1L6)
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Function
- protein arginine N-methyltransferase
- can catalyze formation of omega-N monomethylarginine (MMA) & asymmetrical dimethylarginine (aDMA), with a strong preference for formation of aDMA
- preferentially methylates Arg present in a glycine & arginine-rich domain & displays preference for monomethylated substrates
- specifically mediates asymmetric dimethylation of histone H3 Arg-2 to form H3R2me2a
- H3R2me2a represents a specific tag for epigenetic transcriptional repression & is mutually exclusive with methylation on histone H3 Lys-4 (H3K4me2 & H3K4me3)
- acts as a transcription corepressor of various genes such as HOXA2
- also methylates histone H2A & H4 Arg-3 (H2AR3me & H4R3me, respectively)
- acts as a regulator of DNA base excision during DNA repair by mediating methylation of DNA polymerase beta (POLB), leading to stimulate the polymerase activity by enhancing DNA binding & processivity
- methylates HMGA1
- may play a role in innate immunity against HIV-1 in case of infection by methylating & impairing the function of various HIV-1 proteins such as Tat, Rev & nucleocapsid protein p7
- automethylated
- interacts with (& methylates) HIV-1 Tat, Rev & nucleocapsid protein p7 (NC)
S-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone]
- KM=18.6 uM for AdoMet
- KM=501 uM for WGGYSRGGYGGW peptide
- KM=183.7 uM for WGGYSR(MMA)GGYGGW monomethylated peptide
- Vmax=3.3 nmol/min/mg enzyme with AdoMet as substrate
- Vmax=1.8 nmol/min/mg enzyme with WGGYSRGGYGGW peptide as substrate
- Vmax=3.2 nmol/min/mg enzyme with WGGYSR(MMA)GGYGGW monomethylated peptide as substrate
Structure
- belongs to the protein arginine N-methyltransferase family, PRMT6 subfamily
Compartment
Alternative splicing
named isoforms=2
Expression
highly expressed in kidney & testes