Table 2.

Modification-dependent or modification-stimulated REases described in this work

Representative enzymes	GeneBank Accession # or UniProt ID	Other domains	Putative modification sensing domain	Putative catalytic domain	DNA modification stimulated in vitro activity	Modification dependent restriction (in vivo assays)	Double strand cleavage or nicking activity
TspA15I	WP_020146688		PUA-like	HNH	(g)5hmC, 5hmdU > 5mC	restriction of 5hmC (T4gt) > g5hmC (T4)	ds cleavage (5hmCNG)
VcaM4I	WP_010645282				5hmC > g5hmC, 5hmdU	restriction of 5hmC (T4gt) > g5hmC (T4)
CmeDI	A0A3R2GY07 (UniProt)				5hmC, 5hmdU > g5hmC, 5mC	restriction of 5hmC (T4gt) and g5hmC (T4)
ScoAIV (Sco5333)	NP_629473.1		SRA (SAD-SRA)	HNH	5mC	toxicity to Dcm+ Rec− strains	Strong binding to 5mC
MsiJI	WP_065019168				5mC or 5hmC	toxicity to Dcm+ strains
VcaCI	WP_045378060				5hmC	low toxicity to Dcm+ strains	low activity
AmaNI	WP_084264606	Caspase				low toxicity to Dcm+ strains	low nicking activity
MfoEI, MmaNI, RrhNI, Vsi48I, Vvu009I	WP_064867438				5hmC (5mC not tested)	(?/Unknown)
	WP_084259214
	WP_063758401
	WP_052237964
	WP_060534244
YenY4I	WP_077293998		DUF3427 and PUA-like	PD-(D/E)XK	5mC or 5hmC	restriction of 5hmC (T4gt), λ some toxicity to Dcm+ strains	Low activity in Mn2+
McaZI	WP_064610770		DUF3427	PD-(D/E)XK	binding to 5mC or 5hmC, low activity	restriction of 5hmC (T4gt) toxicity to Dcm+ strains
BwiMMI	WP_000732259				binding to 5mC or 5hmC	restriction of 5hmC (T4gt) some toxicity to Dcm+ strains
EfaL9I	WP_010818586				binding to 5mC or 5hmC	restriction of 5hmC (T4gt) toxicity to Dcm+ strains
ScoA3V (Sco5330)	NP_629471.1		distantly related to PUA	HNH	6mA > A, 5mC	(?/Unknown)	nicking activity (S6mAS)
SRA-nicking domain fusion			SRA domain of ScoA3IV	HNH (gp74)	5mC > C		Nicking near 5mC