Intrafamily heterooligomerization as an emerging mechanism of methyltransferase regulation

Table 1 Disease-associated mutations in residues near methyltransferase interaction interfaces

Protein	Interface	Mutation	Disease	Notes	Refs.
DNMT3A	RD interface	R882H	AML	Significant decrease in catalytic activity and homooligomerization	[24]
		S881N	AML		[83]
		R887I	AML		[83]
	FF interface	R736H	AML	Destabilized interaction interface, but increased stimulation by DNMT3L	[29]
		F732L	AML		[83]
		F772I	AML		[83]
DNMT3B	FF interface	L664P/T	ICF	Differential effects on activity and disruption of oligomerization	[27]
	FF interface	R670Q	ICF	Differential effects on activity and disruption of oligomerization	[27]
	RD interface	H814R	ICF	Significant decrease in catalytic activity and oligomerization	[82]
METTL14	METTL3–METTL14	R298P	Endometrial Cancer	Significant decrease in catalytic activity and ability to distinguish substrate from mutant substrate	[63]
METTL14	METTL3–METTL14	D312Y	Human adult T cell lymphoma/leukemia	Mutation of D312 to A significantly decreased catalytic activity	[63, 83]
PRMT1	PRMT1–PRMT1	W215L	Endometrioid carcinoma-ovary	Significant decrease in catalytic activity, oligomerization, and SAM binding	[84]
		Y220N	Basal cell carcinoma-skin	Significant decrease in catalytic activity, oligomerization, and SAM binding	[84]
		M224V	Adenocarcinoma-colon	Significant decrease in catalytic activity, oligomerization, and SAM binding	[84]
PRMT7	NTD–CTD	R32T	SBIDDS	Residue near NTD–CTD interface in crystal structure	[86]
PRMT7	NTD–CTD	R387G	SBIDDS	Residue near NTD–CTD interface in crystal structure	[86]
METTL11B	METTL11A–METTL11B	D232N	Carcinoma-prostate	Significant decrease in METTL11A–METTL11B interaction	[80, 83]

AML acute myeloid leukemia, ICF immunodeficiency, centromeric instability, and facial anomalies syndrome, NTD N-terminal domain, CTD C-terminal domain, SBIDDS Short Stature, Brachydactyly, Intellectual Developmental Disability, and Seizures syndrome

ISSN: 1756-8935