Protein arginine N-methyltransferase 6

Definition:

Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. Repression of TP53 blocks cellular senescence (By similarity). Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity. Methylates HMGA1. Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator (By similarity). May play a role in innate immunity against HIV-1 in case of infection by methylating and impairing the function of various HIV-1 proteins such as Tat, Rev and Nucleocapsid protein p7 (NC). Methylates GPS2, protecting GPS2 from ubiquitination and degradation (By similarity). Methylates SIRT7, inhibiting SIRT7 histone deacetylase activity and promoting mitochondria biogenesis.

References:

[1]. Nazim El-Andaloussi, et al. Arginine methylation regulates DNA polymerase beta. Mol Cell. 2006 Apr 7;22(1):51-62. [Content Brief]

[2]. Aimee N Iberg, et al. Arginine methylation of the histone H3 tail impedes effector binding. J Biol Chem. 2008 Feb 8;283(6):3006-3010. [Content Brief]

[3]. Frank Herrmann, et al. Dynamics of human protein arginine methyltransferase 1(PRMT1) in vivo. J Biol Chem. 2005 Nov 11;280(45):38005-10. [Content Brief]

[4]. Wei-Wei Yan, et al. Arginine methylation of SIRT7 couples glucose sensing with mitochondria biogenesis. EMBO Rep. 2018 Dec;19(12):e46377. [Content Brief]

[5]. Dawin Hyllus, et al. PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4 trimethylation. Genes Dev. 2007 Dec 15;21(24):3369-80. [Content Brief]

[6]. Jonathan Michaud-Levesque, et al. Thrombospondin-1 is a transcriptional repression target of PRMT6. J Biol Chem. 2009 Aug 7;284(32):21338-46. [Content Brief]

[7]. Ernesto Guccione, et al. Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive. Nature. 2007 Oct 18;449(7164):933-7. [Content Brief]

[8]. Matthew J Harrison, et al. Protein arginine methyltransferase 6 regulates multiple aspects of gene expression. Nucleic Acids Res. 2010 Apr;38(7):2201-16. [Content Brief]

[9]. Adam Frankel, et al. The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity. J Biol Chem. 2002 Feb 1;277(5):3537-43. [Content Brief]

[10]. Tina Branscombe Miranda, et al. Protein arginine methyltransferase 6 specifically methylates the nonhistone chromatin protein HMGA1a. Biochem Biophys Res Commun. 2005 Oct 28;336(3):831-5. [Content Brief]

[11]. Ted M Lakowski, et al. Kinetic analysis of human protein arginine N-methyltransferase 2: formation of monomethyl- and asymmetric dimethyl-arginine residues on histone H4. Biochem J. 2009 Jun 26;421(2):253-61. [Content Brief]

[12]. Baode Xie, et al. Arginine methylation of the human immunodeficiency virus type 1 Tat protein by PRMT6 negatively affects Tat Interactions with both cyclin T1 and the Tat transactivation region. J Virol. 2007 Apr;81(8):4226-34. [Content Brief]

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