Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the PRMT5 gene. [5] [6] PRMT5 symmetrically dimethylates H2AR3, H4R3, H3R2, and H3R8 in vivo, all of which are linked to a range of transcriptional regulatory events. [7]
PRMT5 is a highly conserved arginine methyltransferase that translocated from the cytoplasm to the nucleus at embryonic day ~E8.5, and during preimplantation development at the ~4-cell stage. [8]
Protein arginine methyltransferase 5 has been shown to interact with:
PRMT5 has been shown to interact with CLNS1A, RIOK1 and COPR5 through an interface created by a shallow groove located on the TIM barrel domain of PRMT5 and the consensus sequence GQF[D/E]DA[E/D] located in the terminal regions of the adaptor proteins. [12] [16] The characterisation of the interactions occurring in the binding groove between PRMT5 and peptides derived from the adaptor proteins lead to development of protein-protein interaction (PPI) inhibitors, modulating binding between PRMT5 and the adaptor proteins. [17] [18] Furthermore, Asberry and co-workers synthesised the first-in-class small molecule inhibitor of the PPI between PRMT5 and MEP50. [19] The PPI inhibitors complement a plethora of compounds directly suppressing the enzymatic activity of PRMT5. [20]
Histone methyltransferases (HMT) are histone-modifying enzymes, that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of histone proteins. The attachment of methyl groups occurs predominantly at specific lysine or arginine residues on histones H3 and H4. Two major types of histone methyltranferases exist, lysine-specific and arginine-specific. In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group.
The genomic DNA of eukaryotes associates with histones to form chromatin. The level of chromatin compaction depends heavily on histone methylation and other post-translational modifications of histones. Histone methylation is a principal epigenetic modification of chromatin that determines gene expression, genomic stability, stem cell maturation, cell lineage development, genetic imprinting, DNA methylation, and cell mitosis.
Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.
Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is encoded by the GRB10 gene.
Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene. The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.
Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.
Histone-binding protein RBBP7 is a protein that in humans is encoded by the RBBP7 gene.
Guanine nucleotide-binding protein G(o) subunit alpha is a protein that in humans is encoded by the GNAO1 gene.
5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.
E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the PIAS2 gene.
Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.
Small nuclear ribonucleoprotein Sm D3 is a protein that in humans is encoded by the SNRPD3 gene.
DNA methyltransferase 1-associated protein 1 is an enzyme that in humans is encoded by the DMAP1 gene.
Methylosome subunit pICln is a protein that in humans is encoded by the CLNS1A gene.
Sorting nexin-9 is a protein that in humans is encoded by the SNX9 gene.
Ran-specific binding protein 1 is an enzyme that in humans is encoded by the RANBP1 gene.
Methylosome protein 50 is a protein that in humans is encoded by the WDR77 gene.
Growth factor receptor-bound protein 14 is a protein that in humans is encoded by the GRB14 gene.
Vinexin is a protein that in humans is encoded by the SORBS3 gene.
Protein arginine N-methyltransferase 2 is an enzyme that in humans is encoded by the PRMT2 gene.
Serine/threonine-protein kinase RIO1 is an enzyme that in humans is encoded by the RIOK1 gene.