Table 2 Selected novel domains fused to HEPN domains

AbiJ-NTD1

~ 140 aa; (e.g. 1 to 140 aa,

Mostly alpha helical

Fused to HEPN families: AbiJ, DUF4145 (gi: 113972064), Ymh (gi: 148556575). It is also found fused to other domains potentially involved in biological conflicts: HKD-Phosphoesterases (gi:302346766), STYKinase (gi:47459341), REase (gi: 358072046) and flavodoxin fold nucleoside deoxyribosyltransferase (gi: 397664865)

gi: 134296193, Bcep1808_2091

Burkholderia vietnamiensis G4)

AbiJ-NTD2

~ 100 aa; (e.g. 1 to 102 aa,

Mostly alpha helical with a conserved beta strand next to the first alpha helix

Found fused to AbiJ, and to other domains presumably involved in other domains potentially involved in biological conflicts: Mrr family REase (gi: 91784007), TIR nuclease (gi: 269963288). Many AbiJ_NTD2 sequences have been erroneously included in the DUF3644 Pfam model, a new HEPN domain described here. However, profile-profile searches do not demonstrate an independent relationship between AbiJ_NTD2 and HEPN independently

gi: 60680647, BF1118, Bacteroides fragilis NCTC 9343)

AbiJ-NTD3

~ 140 aa; (e.g. 1 to 142 aa,

Alpha + beta

Found fused to AbiJ. Fused to other domains presumably involved in defense: ABC ATPase (gi:319955098), REase domains prototyped by the Pfam model DUF2726 (gi:56476843)

gi:187251857, Emin_1454,

Elusimicrobium minutum Pei191)

AbiJ-NTD4

~ 160 aa; (e.g. 1 to 165 aa,

Alpha + beta

Found fused to AbiJ and heat repeats (gi: 71907952)

gi: 182417316, CBY_0614,

Clostridium butyricum 5521)

AbiJ-NTD5

~ 100 aa; (e.g. 1 to 115 aa,

Mostly alpha helical

Found fused to AbiJ, and to other domains presumably involved in defense: TIR nuclease (gi:296123260), some have a further N-terminal DnaG-like CxxH-CxxC Zn ribbon domain

gi: 149930787, w0043, Escherichia coli)

AbiTii

~ 180aa; (e.g. 1 to 180 aa of gi: 358446093)

Alpha + beta

Found fused to the N-terminus of the c2405 family of HEPN domains and in few cases to Ymh (gi: 372210551)

HEPN/RES-NTD1

~ 100 aa; (e.g. 1 to 95 aa,

Mostly alpha

Fused to HEPN (MAE_28990 superfamily), RES domain, a potential RNase found in various toxin

gi:206576331, KPK_1764 Klebsiella

helical

systems (gi: 30248753). Also occasionally fused to an ABC ATPase and two other novel domains (Supplementary material). Some of those fused to RES have a further N-terminal Zn ribbon domain

pneumoniae 342

HEPN/Toprim-NTD1

~240 aa; (e.g. 1 to 240 aa, gi: 423201025; HMPREF1167_01188 Aeromonas veronii.

Alpha + beta

Fused to two distinct HEPN families: MAE_28990 and ERFG_01251 families (gi: 118587223), TOPRIM (gi: 160895002) and a Mrr-like REase domain (gi: 383455290)

DpnII/MboI-NTD

~100 aa; (e.g. 1 to 115 aa

Mostly alpha helical with a conserved beta strand next to the first alpha helix

This domain can be unified the α-helical domain found at the N-termini of the type-II REases DpnII and MboI. I It is fused to the HEPN domain prototyped by the Pfam DUF4145 model and to other domains presumably involved in defense: e.g. a novel REase (gi: 146284642)

gi:218440340, PCC7424_3406,

Cyanothece sp. PCC 7424)

ApeA-NTD1

~ 300 aa; (e.g. 1 to 300 aa,

Mostly beta strands

Fused to HEPN (Apea). Several conserved aromatic residues, abundant but poorly conserved

gi: 218441941 PCC7424_5050,

Cyanothece sp. PCC 7424)

MAE_18760-NTD1

~121 aa; (e.g. 1 to 121 of gi: 385800275)

Mostly beta strands

Found at the N-terminus of certain members of the MAE_18760 family

AAA-ATPase (Ava_2192-CTD)

~300aa; (e.g. 160 to 460aa gi:75908411, Ava_2192, Anabaena variabilis)

AAA-ATPase fold

The AAA-ATPase domain overlaps with Pfam DUF499. Fused to HEPN (SWT1/Abi2 family)

wHTH

~65aa ; (e.g. 2006 to 2075 and 2095 to 2161 gi: 323358023, MTES_1575, Microbacterium testaceum)

wHTH fold

Fused to HEPN (SWT1/Abi2 family), along with Transglutaminase and Vsr–family REase domains. Overlaps with DUF3320.

Novel Vsr-REase (MTES_1575_REase)

~180aa (e.g., 1810..1990 aa gi: 323358023, MTES_1575, Microbacterium testaceum)

Vsr REase Fold

Fused to HEPN (SWT1/Abi2 family), along with Transglutaminase and wHTH.

Novel REase (EC042_2821_CTD)

~180aa (eg, 240..420aa gi: 387608267, EC042_2821, Escherichia coli)

REase Fold

Fused to HEPN (EC042_2821) and an N-terminal wHTH in some.