Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PRMT6 (Q96LA8) - Overview - Molecular Target Synopsis

Protein


PRMT6, Protein arginine N-methyltransferase 6
Enzyme Classification 2.1.1.319
UniProt Q96LA8

Also Known as ANM6_HUMAN, PRMT6, HRMT1L6

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). Interacts with EPB41L3 and NCOA1.

6P7I
CRYSTAL STRUCTURE OF HUMAN PRMT6 IN COMPLEX WITH S-ADENOSYL-L- HOMOCYSTEINE AND YS17-117 COMPOUND
RCSB/PDB
Inspect Structure
See all 3D Structures for PRMT6

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
401ENSG00000198890ENST00000361318ENSP00000355145
393ENSG00000198890ENST00000370078ENSP00000359095
375Q96LA8-1
292Q96LA8-2

Sub-cellular localization


UniProt: PRMT6 is active in the following subcellular-locations: nucleus.
GO terms: PRMT6 is active in the following subcellular-locations: cytosol, nucleolus, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRMT6 has gain in 6 cell-lines, loss in 3 cell-lines and no signal in 996 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, K_562, IGROV1

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MCF-7, KPL-1, NCI-H209

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: MCF-7, NHLF, HMEC

(see details)

3D Structures


For PRMT6 there are:
10 structures (21 chains) solved
10 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRMT6 has been screened with 124 compounds (187 bioactivities), 67 compounds have bioactivities that show binding affinity of <= 500nM (73 bioactivities). (see details)