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Table 2 Selected novel domains fused to HEPN domains

From: Comprehensive analysis of the HEPN superfamily: identification of novel roles in intra-genomic conflicts, defense, pathogenesis and RNA processing

Domain name Domain size (Representative and the domain range) Structural and sequence features Comments
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.