Protein arginine N-methyltransferase 5 is an
enzyme that in humans is encoded by the PRMT5gene.[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]
Interactions
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]
^Mulvaney KM, Blomquis C, Acharya N, et al. (Aug 2020). "Molecular basis for substrate recruitment to the PRMT5 methylosome (preprint)".
bioRxiv10.1101/2020.08.22.256347.
^Asberry AM, Cai X, Deng X, et al. (October 2022). "Discovery and Biological Characterization of PRMT5:MEP50 Protein-Protein Interaction Inhibitors". Journal of Medicinal Chemistry. 65 (20): 13793–13812.
doi:
10.1021/acs.jmedchem.2c01000.
PMID36206451.
S2CID252758808.
^Fu S, Zheng Q, Zhang D, et al. (December 2022). "Medicinal chemistry strategies targeting PRMT5 for cancer therapy". European Journal of Medicinal Chemistry. 244: 114842.
doi:
10.1016/j.ejmech.2022.114842.
PMID36274274.
S2CID252956172.
Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9.
doi:
10.1038/nbt810.
PMID12665801.
S2CID23783563.
Miranda TB, Khusial P, Cook JR, et al. (2004). "Spliceosome Sm proteins D1, D3, and B/B' are asymmetrically dimethylated at arginine residues in the nucleus". Biochem. Biophys. Res. Commun. 323 (2): 382–7.
doi:
10.1016/j.bbrc.2004.08.107.
PMID15369763.