Methionine adenosyltransferases in liver cancer

Table 1 Mammalian MAT genes and isoenzymes

Gene	Protein	Amino acids	Alternative names	Oligomeric state	Regulatory subunit	Co-factors	Km for methionine	Km for ATP	Ki for SAMe	X-ray structure
MAT1A	MATα1	395	MATIII MAT(α1)2	Dimer	No		210 μmol/L-7 mmol	1-3 mmol	None	20BV
			MATI MAT(α1)4	Tetramer	No		23 μmol/L-1 mmol	0.2-0.5 mmol	400 μmol/L
MAT2A	MATα2	395	MAT(α2)2	Dimer			4-10 μmol/L	70 μmol/L	60 μmol/L	5A19
			MAT(α2)4	Tetramer						5A1I
MAT2B	MATβV1	334		Monomeric		NADP+
	MATβV2	323		Monomeric		NADP+				2YDX

Historically, MATII in the literature refers to complexes of MATα2 and MATβ.

Table 2 Regulatory mechanisms of human MAT genes and proteins

	MAT1A	MAT2A	MAT2B
Transcriptional regulation	Glucocorticoids (+)	CpG hypomethylation (+)	AP-1 (+)
	C/EBP (+)	Histone H4 acetylation (+)	NFκB (+)
	CpG hypermethylation (-)	c-MYB (+)	SIRT1 (+)
	Histone H4 deacetylation (-)	SP-1 (+)
	c-MYC (-)	AP-1 (+)
	MAFG (-)	NFκB (+)
	c-MAF (-)	HIF1α (+)
		PPARγ (-)
		PPARβ (+)
		HBx (+)
		CREB (+)
Post-transcriptional regulation	AUF1 (-)	HuR (+)	HuR (+)
	miR-485-3p (-)	Methylated-HuR (-)	miR-21-3p (+)
	miR-495 (-)	miR-21-3p (+)
	miR-664 (-)	miR-34a (+)
		miR-34b (+)
Post-translational regulation	Phosphorylation (-)	Phosphorylation (+)	Phosphorylation (+)
	Nitrosylation (-)	Sumoylation (+)	GIT1 interaction (+)
	Oxidation (-)	Acetylation (-)	MATα2 interaction (+)
		MATβ interaction (+)

(+): Positive regulation; (-): Negative regulation.