protein arginine N-methyltransferase 6; heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 6; histone-arginine N-methyltransferase PRMT6 (PRMT6, HRMT1L6)

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] Kinetic parameters: - 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: nucleus Alternative splicing: named isoforms=2 Expression: highly expressed in kidney & testes

General

nuclear protein protein arginine N-methyltransferase (PRMT)

Properties

SIZE: entity length = 375 aa MW = 42 kD COMPARTMENT: cell nucleus MOTIF: glycine-rich region {12-20} Thr phosphorylation site {T21} binding site SITE: 57-57 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 66-66 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 90-90 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 112-112 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 141-141 FOR-BINDING-OF: S-adenosylmethionine

Database Correlations

OMIM 608274 UniProt Q96LA8 Entrez Gene 55170 Kegg hsa:55170 ENZYME 2.1.1.125

References

UniProt :accession Q96LA8