Table 1. Functional domains involved in the synthesis, detection and degradation of c-di-NMPs.

ORGANISM/c-di-NMP/process	Protein name	Functional domain	Interpro/cd identifier	Ref.
BACTERIA
c-di-GMP
Synthesis	diguanylate cyclase (DGC)	GGDEF|Class III nucleotidyl cyclase	IPR000160|IPR001054	(8)
Degradation	EAL	Diguanylate PDE, EAL domain	IPR001633	(8)
	HD-GYP	HD PDEase	IPR003607	(13)
Detection	PilZ	PilZ	IPR009875	(7)
	FleQ	unknown		(24)
	Clp	unknown		(26)
	Bcam1349	unknown		(27)
	FimX	EAL substrate binding site	IPR001633	(55)
	PelD	RxxD motif in GGDEF domain	IPR000160	(29)
	PNPase	unknown		(35)
	Vpst	unknown		(25)
	Vc2 Class I Riboswitch	GEMM		(36)
c-di-AMP
Synthesis	diadenylate cyclase	DisA_N	IPR003390	(3)
Degradation	YybT/GdpP	RecJ-like phosphoesterase	IPR001667	(39)
Detection	DarR	GATase1_AraC_1	cd03137	(44)
c-AMP-GMP
Synthesis	DncV (VC0179)	no previously identified domain		(4)
Degradation	unknown
Detection	unknown
DICTYOSTELIA
c-di-GMP
Synthesis	diguanylate cyclase (DgcA)	GGDEF|Class III nucleotidyl cyclase	IPR000160|IPR001054	(45)
Degradation	unknown
Detection	unknown
METAZOA
2′3′cGAMP
Synthesis	Cyclic GMP-AMP synthase (cGAS)	MAB21 (male abnormal 21)	IPR024805	(50)
Degradation	unknown
Detection	STING	STING-C	cd12146	(50)