Tchem PRMT6 Protein arginine N-methyltransferase 6

Protein Summary

Description

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 (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910). Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910). Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a (PubMed:17898714, PubMed:18079182, PubMed:18077460). H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3) (PubMed:17898714, PubMed:18077460). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53 (PubMed:19509293). 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 (PubMed:16600869). Methylates HMGA1 (PubMed:16157300, PubMed:16159886). 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. 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) (PubMed:17267505). Methylates GPS2, protecting GPS2 from ubiquitination and degradation (By similarity). The protein encoded by this gene belongs to the arginine N-methyltransferase family, which catalyze the sequential transfer of methyl group from S-adenosyl-L-methionine to the side chain nitrogens of arginine residues within proteins, to form methylated arginine derivatives and S-adenosyl-L-homocysteine. This protein can catalyze both, the formation of omega-N monomethylarginine and asymmetrical dimethylarginine, with a strong preference for the latter. It specifically mediates the asymmetric dimethylation of Arg2 of histone H3, and the methylated form represents a specific tag for epigenetic transcriptional repression. This protein also forms a complex with, and methylates DNA polymerase beta, resulting in stimulation of polymerase activity by enhancing DNA binding and processivity. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• Q96LA8
• A3KME1
• B4DID8
• Q5T5Y5
• Q6DKI4
• Q9NVR8

Gene Name

• PRMT6

Ensembl ID

• ENST00000370078
• ENSP00000359095
• ENSG00000198890

Symbol

• HRMT1L6
• HRMT1L6

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.76
cell type or tissue	0.72
molecular function	0.7
transcription factor binding site profile	0.69
virus perturbation	0.68

Protein Classes

DTO Classes

Protein / Epigenetic Regulator / Writer / Protein Methyltransferase / Protein Arginine Methyltransferase / Protein Arginine N-methyltransferase 6

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 83.47   (req: < 5)

Gene RIFs: 56   (req: <= 3)

Antibodies: 353   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 83.47   (req: >= 5)

Gene RIFs: 56   (req: > 3)

Antibodies: 353   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 72

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0