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Table 2 Phyletic distribution, export pathways, and contextually-associated domains and proteins of polymorphic toxin domains

From: Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics

Toxin1 Fold; conserved residues or motifs2and additional notes Phyletic spread3 Export pathway4 Immunity proteins Repeats/processingProteases
DNase toxins
Tox-NucA HNH/EndoVII fold; GH, N, N, E Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chloroflexi, firmicutes, spirochaetes, verrucomicrobia T2SS, T5SS, T6SS, T7SS (WXG,LXG,LDXD), PVC Imm36, Imm-SUKH, Imm-NTF2 Proteases: PVC-Metallopeptidase, Caspase; Repeats: FilH, RHS, Tail-fiber
Tox-ColE7 HNH/EndoVII fold (PDB: 1zns);HH, H, H Bacteroidetes, α,γ,δ,ϵ-proteobacteria, firmicutes T2SS, T5SS, T6SS, T7SS (WXG,LXG), PyocinS Imm-ColE7, Imm-SUKH Repeats: FilH, RHS
Tox-HNH (including Tox-HNH-CIDE) HNH/EndoVII fold; A DHxxE characterizes the Tox-HNH-CIDE clade. Acidobacteria, actinobacteria, bacteroidetes, chlorobi, firmicutes, proteobacteria, Eukaryotes :metazoa T2SS, T5SS, T7SS (WXG,LXG, LDXD), PVC, TcdB/TcaC Imm-SUKH, Imm-SuFu, Imm14, Imm18, Imm24, Imm33, Proteases: PVC-Metallopeptidase, HINT, Tox-PLOTU, ZU5; Repeats: FilH, RHS
Tox-AHH HNH/EndoVII fold; [AG]HH, N, H, H, Y motif and residues Actinobacteria, α,β,γ,δ,ϵ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, fusobacteria, lentisphaerae, planctomycetes, spirochaetes, verrucomicrobia, eukaryotes: hexapoda, Viruses: Ostreococcus lucimarinus virus, Bathycoccus sp. RCC1105 virus T2SS, T5SS, T6SS, T7SS (LXG, WXG, LDxD), TcdB/TcaC Imm-PA2201, Imm-ank, Imm11, Imm20, Imm23, Imm24, Imm43 Proteases: HINT; Repeats: RHS, FilH
Tox-DHNNK HNH/EndoVII fold; DH, N, N, N, K motif and residues Acidobacteria, actinobacteria α,β,γ,δ,ϵ-proteobacteria, firmicutes, fusobacteria, planctomycetes, spirochaetes, archaea: euryarchaeota, eukaryotes: fungi(ascomycota, basidiomycota) T2SS, T6SS, T7SS (LXG, LDXD,WXG), PVC Imm-SUKH, Imm-SuFu, Imm33 Proteases: PVC-Metallopeptidase, HINT
Tox-EHHH HNH/EndoVII fold; [ED]H, H, H Actinobacteria, bacteroidetes, β,γ,δ-proteobacteria, firmicutes T2SS, T5SS T6SS, T7SS (WXG, LxG), TcdB/TcaC Imm8, Imm50 Repeats: FilH, RHS
Tox-GH-E HNH/EndoVII fold; GH, E, N, E motif and residues Actinobacteria, bacteroidetes, β,γ,δ,ϵ-proteobacteria, chloroflexi, firmicutes, planctomycete, spirochaetes, archaea: euryarchaeota T2SS (MafBN), T5SS, T6SS, T7SS (WXG, LxG, LDXD), PVC Imm-SuFu, Imm-ank Proteases: HINT, PVC-Metallopeptidase; Repeats: RHS, FilH, Tail Fiber
Tox-GHH HNH/EndoVII fold; WxxE, W, G[HQ]H, NIxF, [DE]H; Eukaryotic versions lack the conserved histidines and a C-terminal helix Acidobacteria, bacteroidetes, firmicutes, γ-proteobacteria, planctomycete, eukaryotes: metazoa T2SS, T6SS, T7SS (LXG), TcdB/TcaC Imm-SUKH Repeats: RHS
Tox-GHH2 HNH/EndoVII fold; s[AGP]HH, HxxxH β,γ-proteobacteria, bacteroidetes, firmicutes T2SS, T6SS - Repeats: RHS
Tox-HHH HNH/EndoVII fold; N, s[GD]xxR, HHH, H Actinobacteria, bacteroidetes, γ-proteobacteria, firmicutes T2SS, T5SS,T6SS, T7SS (LXG,LDXD), PVC Imm-SUKH Proteases: PVC-Metallopeptidase; Repeats: FilH, RHS
Tox-LHH HNH/EndoVII fold; N, LHH, E, H, H, W Actinobacteria, α,β,γ,δ,ϵ-proteobacteria, bacteroidetes, firmicutes, fusobacteria, planctomycetes T2SS, T5SS, T6SS, T7SS (WXG,LXG), PVC Imm-SUKH Proteases: PVC-Metallopeptidase, HINT; Repeats: FilH, RHS, Tail-fiber
Tox-SHH HNH/EndoVII fold; [SG]HH, H motif and residue Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, planctomycetes, eukaryotes: crustacea, viruses : caudovirales T2SS, T5SS, T6SS, T7SS (LDXD, LXG, WXG) Imm-SUKH, Imm11, Imm24, Imm30, Imm55 Proteases: HINT Repeats: FilH, RHS, ALF
NGO1392-like (Also known as Tox-SuFu-Nuc) HNH/EndoVII fold; CxxC, DH, CXXC, Q Actinobacteria, α,β,γ,δ-proteobacteria, chlorobi, chloroflexi, cyanobacteria, firmicutes, spirochaetes, eukaryotes: alveolata(apicomplexa), choanoflagellida, metazoa, stramenopiles, viridiplantae, Viruses: several Mycobacteriophages, caudovirales T2SS (MafBN), T5SS, TcdB/TcaC, PVC Imm-SuFu, Imm13, Imm21, Imm33, Imm38 Proteases: HINT, PVC-Metallopeptidase, ZU5; Repeats: FilH, RHS, Tail fiber
Tox-WHH HNH/EndoVII fold; WHH, L, H, HxG Actinobacteria, α,β,γ,δ,ϵ-proteobacteria, bacteroidetes, chloroflexi, firmicutes, fusobacteria, planctomycete, synergistetes T2SS, T5SS, T6SS, T7SS (WXG, LXG, LDXD), PVC, TcdB/TcaC Imm-SUKH, Imm28, Imm37 Proteases: HINT, PVC-Metallopeptidase; Repeats: RHS, ALF, FilH
Tox-REase-1 Restriction endonuclease fold; E, D, ExK, Q Actinobacteria, bacteroidetes, β,γ,ϵ-proteobacteria, cyanobacteria, fusobacteria, firmicutes, gemmatimonadetes, planctomycetes, eukaryotes: alveolata, heterolobosea T2SS,T5SS, T6SS, T7S (WXG,LXG), TcdB/TcaC Imm-PA2201, Imm49 Proteases: HINT, Caspase, ZU5; Repeats: FilH, RHS, Tail-fiber
Tox-REase-2 Restriction endonuclease fold; E, DG, [DE]xK, T, W Actinobacteria T2SS, T7SS (WXG), PrsW - Proteases: PrsW-peptidase
Tox-REase-3 Restriction endonuclease fold; [KR]ExD, K, ExQxK β,γ-proteobacteria, firmicutes T2SS (MafBN), T6SS, T7SS (WXG), PrsW Imm-SUKH, Imm7 Proteases: PrsW-peptidase; Repeats: RHS
Tox-REase-4 Restriction endonuclease fold; D, ExK Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, planctomycetes, spirochaetes, eukaryotes: stramenopiles T2SS, T5SS, T6SS, T7SS (WXG,LDXD), PrsW Imm-SUKH, Imm22, Imm54 Proteases: PrsW-peptidase; HINT; Repeats: FilH, RHS, Tail fiber
Tox-REase-5 Restriction endonuclease fold; Y, FDG, EAK, Y, Q,W Actinobacteria, α,β,γ,δ-proteobacteria, firmicutes, fusobacteria, Viruses: caudovirales T2SS, T5SS, T6SS, PrsW Imm52 Proteases: PrsW-peptidase; Repeats: FilH, RHS
Tox-REase-6 Restriction endonuclease fold; E, D, ExK, Q, Y Actinobacteria, α,β,γ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, eukaryotes: heterolobosea T2SS, T5SS, T6SS, T7SS (WXG), PrsW Imm49 Proteases: PrsW-peptidase; Repeats: RHS, Tail fiber
Tox-REase-7 Restriction endonuclease fold; GxxxE, IxD, ExK, Q Actinobacteria, α,γ,ϵ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, planctomycetes, verrucomicrobia T2SS, T5SS, T6SS, T7SS (WXG) ImmHEAT, Imm23, Imm54 Proteases: HINT; Repeats: FilH, RHS, Tail-fiber
Tox-REase-8 Restriction endonuclease fold; GxxxQ, DD, QxK Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chlorobi, chloroflexi, firmicutes, spirochaetes, verrucomicrobia, eukaryotes: metazoa(crustacea, hexapoda,placozoa) T2SS (APD1) - Repeats: Ankyrin repeats, TPR repeats, RHS
Tox-Rease-9 Restriction endonuclease fold; GxxxH, E, D, ELKP, YxxE Actinobacteria, γ-proteobacteria, bacteroidetes, chlamydiae, firmicutes T2SS, T7SS (LxG) Imm54 Proteases: HINT; Repeats: RHS
Tox-Rease-10 Restriction endonuclease fold; E, Q, [DE], ExKNY, R, DxRG β,γ,ϵ-proteobacteria, firmicutes, fusobacteria, spirochaetes T2SS, T5SS, T7SS (WXG, LXG), Imm54, Imm70 Repeats: FilH
Tox-URI1 URI nuclease fold; Y, YxG, R, [RK]xxE, N Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chlamydiae, chloroflexi, firmicutes, lentisphaerae, nitrospirae, verrucomicrobia, archaea: euryarchaeota, v iruses: Ostreococcus lucimarinus virus , eukaryotes: fungi T2SS, T5SS, T6SS, TcdB/TcaC Imm14, Imm26, Imm44, Imm51 Proteases: HINT; Repeats: RHS, FilH, Tail fiber
Tox-URI2 URI nuclease fold; Y, KxG, [EQ] Actinobacteria, α,β,γ-proteobacteria, bacteroidetes, firmicutes T2SS, T6SS Imm9, Imm39, Imm12, Imm44 Proteases: HINT; Repeats: RHS, Tail fiber
RNase toxins of known fold
Tox-Barnase Barnase-EndoU-ColicinE5/D-RelE like nuclease (BECR) fold (α + β); H, H, [ST], FP, [STD] Actinobacteria, bacteroidetes, β,γ,δ,ϵ-proteobacteria, chlamydiae, chloroflexi, cyanobacteria, deinococci, fibrobacteres, firmicutes, fusobacteria, nitrospirae, planctomycetes archaea: euryarchaeota T2SS, T6SS, T7SS (WXG), TcdB/TcaC, MuF, PVC Imm-Barstar Proteases: PVC-Metallopeptidase; Repeats: RHS
Tox-Colicin D BECR fold (α + β); (PDB: 1v74); [KH]K, Hxx[ED], [ST], [TS]xxK; Of the conserved residues in ColicinD (PDB: 1v74), K607, K608, H611, D614, and S677 are essential for activity β,γ,δ-proteobacteria, chloroflexi, firmicutes, spirochaetes, archaea: euryarchaeota, eukaryotes: fungi (ascomycota) T2SS, T5SS, Cloacin, TcdB/TcaC, PVC, MuF ImmD, Imm64; ImmD is the major immunity protein share with plasmid borne colicin systems Proteases: PVC-Metallopeptidase; Repeats: RHS, FilH
Tox-ColicinC/E5 tRNase BECR fold (α + β, PDB: 2dfx); K, W, Y, Y, Q, [RK], W; Of the conserved residues in Colicin E5 (PDB: 2dfx), Y81 and S95 are predicted to be involved in catalysis β,γ-proteobacteria, firmicutes, Plasmid ColE5-099 T2SS, T5SS, T7SS (LXG), Cloacin/PyocinS, TcdB/TcaC ImmE5 Repeats: RHS, FilH
Tox-EndoU (including XendoU) BECR fold (α + β, PDB: 2c1w); H, H, [SNT],[SNT]; This structural core contains two BECR fold units, where the N-terminal unit has lost strand-4, while the helix in the C-terminal unit has flipped to the opposite end. In 2c1w, H162 and T278 form one pair of catalytic residues and H178 and S229 form the other. Some members use a Mn2+ probably as a transition state stabilizer Actinobacteria, α,β,γ-proteobacteria, bacteroidetes, chlamydiae, cyanobacteria, fibrobacteres, firmicutes, fusobacteria, tenericutes, eukaryotes: hemichordata, viridiplantae, stramenopiles, metazoa T2SS (MafBN), T5SS, T6SS, T7SS (WXG,LXG) Imm-SUKH, Imm-SuFu, Imm28 Proteases: HINT; Repeats: FilH, RHS
Tox-RelE BECR fold (α + β); [KR], R; The active site residues in the classical RelE (PDB: 3kha) correspond to residues R61 and R81 Actinobacteria, α, γ, -proteobacteria, bacteroidetes, cyanobacteria, firmicutes, fusobacteria T2SS Imm54 Proteases: HINT; Repeats: RHS
Ntox7 Predicted BECR fold (α + β); DGx + xhR, N motif Actinobacteria, bacteroidetes, β,γ, δ- proteobacteria, chlamydiae, chloroflexi, firmicutes T2SS (MafBN), T2SS (APD1), T5SS, T7SS, TcdB/TcaC Imm8, Imm31, Imm32, Imm-NMB0513, Imm-SuFu; Imm8 is the predominant immunity protein across a wide phyletic range Proteases : HINT, ZU5; Repeats: FilH, RHS
Ntox19 Predicted BECR fold (α + β); D,H,DxxxR,E,HxxF; Also found in mimivirus, where it is fused to ankyrin repeats, β,γ,δ- proteobacteria, firmicutes, fusobacteria, bacteroidetes, Viruses: Acanthamoeba polyphaga mimivirus T2SS (MafBN), T5SS, T7SS (LxG and WxG), TcdB/TcaC Imm38, Imm40. These associations are seen across many different bacterial lineages Repeats: FilH, RHS
Ntox21; Also referred to as the E. clocae CdiAC; Shown to be a tRNAse Predicted BECR fold (α + β); K, [DS]xDxxxH, K, RxG[ST], RxxD Actinobacteria, α,β,γ-proteobacteria bacteroidetes, firmicutes T2SS (MafBN), T5SS, T4SS, T7SS Imm-Barstar, Imm41 Proteases : HINT; Repeats: RHS, FilH
Ntox35 Predicted BECR fold (α + β); H, KH Actinobacteria, bacteroidetes, β-proteobacteria, chlamydiae, chloroflexi, firmicutes, planctomycetes T2SS (MafBN) - Repeats: RHS
Ntox36 Predicted BECR fold (α + β); N, [RY], [DE] Acidobacteria, actinobacteria, β,γ-proteobacteria, cyanobacteria, elusimicrobia, firmicutes T2SS, T5SS - Proteases: HINT; Repeats: RHS, FilH
Ntox41 Predicted BECR fold (α + β); [RK]H, [KR], [ST]xxP Actinobacteria, α,β,γ-proteobacteria, bacteroidetes, firmicutes, planctomycetes T2SS, T5SS, T7SS (WXG,LXG) - Proteases: HINT; Repeats: RHS, FilH, ALF
Ntox47 Predicted BECR fold (α + β); D, [HRK], RT, E, D, PH, H, [DE], R β,γ-proteobacteria, firmicutes T2SS, T6SS, T7SS (LXG,WXG) - Proteases: HINT; Repeats: RHS
Ntox48 Predicted BECR fold (α + β); R, [RK], Q, Q Acidobacteria, actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, fusobacteria, planctomycetes T2SS, T5SS, T6SS T7SS (WXG,LXG), Imm60, Imm62, Imm66, Imm71 Proteases: HINT; Repeats: RHS, FilH
Ntox49 Predicted BECR fold (α + β); H, [KR] Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chlamydiae, chloroflexi, cyanobacteria, firmicutes, thermotogae, archaea: euryarchaeota, eukaryotes: stramenopiles, viridiplantae, viruses: caudovirales T2SS (MafBN), T5SS, T7SS (WXG,LXG), MuF, PVC Imm22 Proteases: PVC-Metallopeptidase, HINT, ZU5; Repeats: RHS
Ntox50 Predicted BECR fold (α + β); H, S, K, T, H, K, HxVP Actinobacteria, β,γ,δ-proteobacteria, chlamydiae, firmicutes, fusobacteria, viruses: caudovirales T2SS (MafBN), T6SS, T7SS (WXG,LXG), MuF - Proteases: HINT
Predicted metal-independent RNase toxins
Tox-CdiAC All-β; N, [DSN],E β,γ,δ-proteobacteria T2SS, T5SS, T6SS, TcdB/TcaC Imm-CdiI, Imm5 + Imm36. Imm-CdiI is the most prominent immunity protein to this toxin Repeats: RHS, FilH
Tox-ColE3 All-β; ColE3 cytotoxic ribonuclease fold, R, Dxx + [HK], E, H Actinobacteria, α,β,γ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, fusobacteria T2SS (MafBN), T5SS, T7SS (WXG,LXG) Imm-Cloacin, Imm45 Proteases: HINT; Repeats: RHS, FilH
Tox-RES; PF08808 in Pfam. Also found in toxin-antitoxin systems (see text); α + β; R, R, E, S Acidobacteria, actinobacteria, α,β,γ,δ,ϵ-proteobacteria, bacteroidetes, chlorobi, chloroflexi, cyanobacteria, deinococci, firmicutes, nitrospirae, spirochaetes, synergistetes, verrucomicrobia, Viruses: caudovirales T2SS, T5SS, T6SS Imm51, Antitoxin-DUF2384(in AT system) Repeats: RHS, FilH
Ntox2 α + β + α-helical C-terminus; GEsH motif and conserved E, RE, H and K; Multiple copies in the same gene neighborhood in Microscilla Microscilla marina (Bacteroidetes) PVC - Proteases: PVC-Metallopeptidase
Ntox4 α + β; Several charged residues Nitrosococcus, Frankia PVC - Proteases : PVC-Metallopeptidase
Ntox5 α + β; Several charged residues Streptomyces, Nitrobacter PVC - Proteases : PVC-Metallopeptidase
Ntox9 Mostly β; RxY, E, WxE and H; Catalytic mechanism likely to be similar to that of Colicin-E3 Actinobacteria, α,β,γ-proteobacteria bacteroidetes, chlamydiae, fusobacteria T2SS (MafBN), T5SS, T6SS - Proteases: PrsW peptidase; Repeats: RHS
Ntox12 All-β; D, D, H Actinobacteria, chlamydiae, firmicutes, α,β,γ- proteobacteria T2SS, T5SS T6SS, T7SS (WxG and LxG), TcdB/TcaC Imm32; Note immunity protein also present in intracellular parasite Odyssella Proteases: OUT; Repeats: RHS, FilH
Ntox13 β/α, KxxxxxxE motif Firmicutes, β-proteobacteria T2SS Imm59 Repeats: RHS
      Proteases: Transglutaminase
Ntox15 Mostly α, HxxD motif Actinobacteria, firmicutes, α,β,γ- proteobacteria T2SS, T6SS, T7SS (LDxD and LxG), PVC Imm-SUKH Proteases: PVC-Metallopeptidase, HINT
Ntox16 α-helical domain; R, [DNE]xxH; part of polytoxin in Xanthomonas fuscans Cyanobacteria, β,γ, δ proteobacteria, verrucomicrobia T2SS, T6SS, PVC - Proteases: PVC-Metallopeptidase; Repeats: RHS
Ntox17 Mostly β; ExD, H, several charged residues α,β,γ proteobacteria, firmicutes T2SS (MafB), TcdB/TcaC, T7SS Imm31; association widespread several lineages Repeats: RHS
Ntox20 Mostly β; conserved R Acidobacteria, α,β,γ,ϵ-proteobacteria T2SS (MafBN), T5SS Imm-NMB0513, Imm-SUKH Imm28 Repeats: FilH
Ntox23 All-β; Bacteroidetes T2SS, TcdB/TcaC - Repeats: RHS
  ND, DxxR, H     
Ntox24 All-β; Y, H, H; Also found in Toxin-Antitoxin systems (see text) Actinobacteria, α,β,γ-proteobacteria, chlamydiae, chloroflexi, firmicutes, fusobacteria T2SS, T5SS T7SS (WXG,LXG), MuF Imm50, Imm53 Proteases: HINT; Repeats: RHS, FilH
Ntox25 Mostly β; FGPY motif α,γ-proteobacteria, bacteroidetes T2SS, T5SS - Repeats: FilH
Ntox27 α + β; D, E, RxW Actinobacteria, bacteroidetes, fusobacteria T2SS, T7SS (WXG) - Proteases: HINT; Repeats: ALF, RHS
Ntox28 All-α; D,K[DE], [DN]HxxE, E Actinobacteria, α,γ-proteobacteria, firmicutes T2SS, T5SS T7SS (WXG) - Repeats: FilH
Ntox31 α + β; K, E, E Actinobacteria, α,γ-proteobacteria, bacteroidetes, firmicutes, eukaryotes: ciliophora T2SS, T5SS, T6SS, T7SS (WXG, LXG) Imm62 Repeats: RHS, FilH
Ntox32 All-α; H, [KR], [ED], [DE] Bacteroidetes, α,γ-proteobacteria, firmicutes, eukaryotes: insects T2SS - Proteases: Peptidase S8 (Subtilisin family); Repeats: RHS
Ntox34 All-α; GNxxD, K, C, C, K, WxCxH and other charged residues γ,δ,ϵ-proteobacteria, firmicutes T2SS, T6SS Imm-HEAT Repeats: RHS
Ntox37 All-β; E, [KR] Hx[DH] Actinobacteria, γ-proteobacteria, chlamydiae, chloroflexi, firmicutes T2SS, T7SS(WXG) Imm32 Proteases: Tox-PLOTU; Repeats: RHS
Ntox39 All-β; Several basic residues Firmicutes T2SS - Repeats: RHS
Ntox40 All-β; DRxxG, R, Y Acidobacteria, actinobacteria, α,β,γ,ϵ-proteobacteria, bacteroidetes, firmicutes, planctomycetes, synergistetes, eukaryotes: fungi T2SS, T5SS, T6SS, T7SS (WXG,LXG,LDXD), TcdB/TcaC Imm35, Imm36, Imm59, Imm60, Imm61, Imm63 Repeats: RHS, FilH
Ntox42 α + β; GK, ExxxH, DxYxF[ED] Firmicutes (negativicutes) T5SS - Repeats: FilH
Ntox44 All-α; DxK, GNxxxG, and DxxxD. Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chloroflexi, firmicutes, proteobacteria, spirochaetes, eukaryotes: fungi (microsporidia) T2SS, T6SS, T7SS(WXG,LXG) - Proteases: Papain-like protease; Repeats: RHS, ALF
Predicted RNase toxins with two conserved histidine residues
Tox-EDA39C α + β; H, Sx[HS]Y; Present in a wide range of eukaryotes where it might be a defensive RNAse Acidobacteria, actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chlamydiae, chloroflexi, firmicutes, gemmatimonadetes, planctomycetes, verrucomicrobia, eukaryotes: plants, chlorophytes, fungi, dictyosteliida, stramenopiles T2SS, T5SS, T6SS, T7SS (LXG) Imm-SuFu Proteases: HINT; Repeats: RHS
Ntox18 α/β; H, S, H α,β,γ- proteobacteria, bacteroidetes, chloroflexi, cyanobacteria, firmicutes, eukaryotes: metazoan: Lateral transfer to Branchiostoma T2SS (MafBN), T2SS Imm29, Imm42; Imm29 association is widespread across bacteria Proteases: HINT; Repeats: RHS, FilH
Ntox22 Mostly β, D, D, H, E, H Ralstonia, Burkholderia phymatum T5SS - Repeats: FilH
Ntox26 α + β; KHxx[DE], Q, W, H Actinobacteria, α,β,γ-proteobacteria, firmicutes, fusobacteria T2SS, T5SS T7SS (LXG) - Proteases: HINT; Repeats: RHS, FilH, Tail fiber
Ntox30 All-β; RxH, R THIP Actinobacteria, bacteroidetes, α,γ-proteobacteria, firmicutes, spirochaetes T2SS, T6SS, T7SS (WXG, LXG), TcdB/TcaC - Repeats: RHS
Ntox43; Pseudomonas RhsT-C belongs to this clade α + β; with two conserved H Actinobacteria, γ,δ-proteobacteria, firmicutes, verrucomicrobia T2SS, TcdB/TcaC - Repeats: RHS
Tox-JAB-1 Deaminase fold (α + β); NxxxE, HxH, S, D Bacteroidetes T2SS Imm65 Repeats: RHS
Tox-JAB-2 (DUF4329 in Pfam) Deaminase fold (α + β); E, H[ST]H, S, D α,γ,δ-proteobacteria bacteroidetes, cyanobacteria, firmicutes, eukaryotes: fungi (ascomycota), viruses: caudovirales T2SS, T6SS, T7SS (WXG), TcdB/TcaC Imm-NTF2 family 2 Repeats: RHS
Tox-ComI α + β fold; DE motif Actinobacteria, α,β,γ-proteobacteria, bacteroidetes, firmicutes, verrucomicrobia, eukaryotes: dictyosteliida, fungi (ascomycota, basidiomycota), viruses: Bacillus phage SP10 T2SS, T6SS Imm-ComJ, Imm-SUKH Proteases: HINT; Repeats: RHS
Tox-HET-C All-α; H, [DE], HxD, HxxxDxxxH, Nxx[DE], [ST]G; We predict that the Het-C domain is related to phospholipase C and the S1-P1 nuclease and shares a common active site and fold (see text) Actinobacteria, cyanobacteria, γ,δ-proteobacteria, dictyoglomi, eukaryotes: fungi (ascomycota, basidiomycota), metazoa T2SS, T6SS, PVC - Proteases: PVC-Metallopeptidase
Ntox29 All-β; D,D, HxE, D, K, R residues β,γ-proteobacteria, firmicutes T2SS, T5SS,T7SS (LXG) Imm41 Proteases: HINT; Repeats: RHS, FilH
Predicted RNase toxins with uncertain metal dependence
Ntox1 α + β fold; C, C, H, E Acidobacteria, α-proteobacteria PVC   Proteases: PVC-Metallopeptidase
Ntox3 All-β; several charged residues including as D, R, H, C; associated with Annexin domain in Haliangium Haliangium (δ-proteobacteria), Microscilla (Bacteroidetes) PVC - Proteases: PVC- Metallopeptidase; Repeats: Annexin
Ntox6 α + β; several charged residues; Microcoleus(Cyanobacteria), Haliangium(δ-proteobacteria) PVC - Proteases: PVC- Metallopeptidase
Ntox8 α + β fold; HxR and HxxxH motifs β-proteobacteria, bacteroidetes, firmicutes, eukaryotes: dictyosteliida T2SS, T6SS Imm16 Repeats: RHS
Ntox10 α + β; Several charged residues Bacteroidetes, verrucomicrobia T2SS Imm27, Imm53; Imm27 primary immunity protein across most lineages Repeats: RHS
      Proteases: Transglutaminase
Ntox11 α/β followed by β rich C-terminus; N-terminal GxR, RxxxoH motif, C-terminal domain has H, GxE, GxxH and an acidic residues; Naegleria possibly secreted Actinobacteria, cyanobacteria, firmicutes α, δ,γ-proteobacteria, eukaryotes: Trichoplax, Naegleria PVC - Proteases: PVC- Metallopeptidase
Ntox14 α + β; Several charged residues Desulfobacca, Pelobacter (δ-proteobacteria) PVC Imm22 Proteases: PVC-Metallopeptidase
Ntox33 α + β; [DN]xHxxK, DxxxD Actinobacteria, cyanobacteria, firmicutes, γ-proteobacteria, verrucomicrobia T2SS - -
Ntox45 α + β; DxD motif Actinobacteria, α-proteobacteria, bacteroidetes T2SS - Proteases: HINT; Repeats: RHS
Other toxins that act on nucleic acids
Tox-Deaminase Deaminase fold (α + β); [HCD]xE, CxxC; As previously reported, nine distinct families of deaminase belonging to two distinct clades are present in polymorphic toxin systems as toxins. We report two additional families below Acidobacteria, actinobacteria, bacteroidetes, chlorobi, cyanobacteria, firmicutes, α,β,γ,δ,-proteobacteria Eukaryotes : See text and previous publication T2SS (MafBN), T5SS, T6SS, T7SS (WXG, LDXD, LXG), PVC, TcdB/TcaC Imm1, Imm2, Imm3, Imm4, Imm5, Proteases: PVC-Metallopeptidase, HINT, CPD, PrsW peptidase, Caspase; Repeats: RHS, FilH, ALF, PPR
     Imm6, Imm10, Imm18, Imm-SUKH, Imm-ank  
Tox-Deaminase (sce3516-like) Deaminase fold (α + β); H[occasionally D]xE, CxxC; Toxins of this family belong to the strand-hairpin clade of deaminases Actinobacteria, β,γ,δ,-proteobacteria T2SS, T5SS, T6SS T7SS, TcdB/TcaC Imm-SUKH Proteases: HINT
      Repeats: RHS, FilH
Tox-Deaminase (WD0512-like) Deaminase fold (α + β); CxE, CxxC; Toxins of this family belong to the Helix-4 clade of deaminases. These proteins additionally contain a C-terminal toxin, the Tox-Latrotoxin-CTD α- proteobacteria (Wolbachia) T2SS - Repeats: RHS
Tox-ParB ParB fold (α + β); R Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, firmicutes T2SS (MafBN), T5SS, T6SS, T7SS (WXG), PVC Imm20, Imm27, Imm-SuFu Proteases: PVC-Metallopeptidase, HINT; Repeats: RHS, FilH
Tox-ParBL1 Predicted ParB fold (α + β); [ST], [NT][RT][RT]; note the latter two residues of this motif are mostly R Actinobacteria,α,β,γ-proteobacteria, firmicutes, euryarchaea, eukaryotes: stramenopiles, viridiplantae, ascomycota, chlorophyta, choanoflagellida,metazoa,ciliophora, kinetoplastida T2SS (MafBN), T5SS, T6SS, T7SS (WXG, LXG) Imm-SUKH, Imm44 Proteases: HINT; Repeats: FilH, RHS
Tox-HTH HTH fold; RxxY, R, [ST] Acidobacteria, actinobacteria, α,β,γ,δ,ϵ-proteobacteria, bacteroidetes, cyanobacteria, firmicutes, proteobacteria, archaea, eukaryotes: ascomycota, viridiplantae, T2SS, T5SS, T6SS, T7SS (LXG, WXG, LDXD), PVC, MuF - Proteases: PVC-Metallopeptidase; Repeats: FilH
Peptidase toxins
Tox-ALFMetallopeptidase(Anthrax lethal factor) metallopeptidase fold (α + β); HExxH Actinobacteria, bacteroidetes, δ-proteobacteria, firmicutes, fibrobacteres PVC, T2SS Imm-SuFu Proteases: PVC-Metallopeptidase
      Repeats: FilH
Tox-HopH1 metallopeptidase fold (α + β); HExxH, [DE]N Actinobacteria, α,β,γ-proteobacteria bacteroidetes, planctomycetes T2SS,T3SS,T5SS, T6SS,T7SS (WXG), PVC, TcdB/TcaC - Proteases: PVC-Metallopeptidase, ZU5, caspase; Repeats: RHS
Tox-MPTase1 metallopeptidase fold (α + β); HExxH Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chlorobi, cyanobacteria, deinococci, planctomycetes, spirochaetes, thermotogae T2SS,T7SS (WXG), TcdB/TcaC - Repeats: RHS
Tox-MPTase2 metallopeptidase fold (α + β); Y, HExxH, Bacteroidetes TcdB/TcaC - Proteases: ZU5; Repeats: RHS
Tox-MPTase3 metallopeptidase fold (α + β); K, HExxH, F[DE] α-proteobacteria, bacteroidetes T2SS, PVC - Proteases: PVC-Metallopeptidase; Repeats: RHS
Tox-MPTase4 metallopeptidase fold (α + β); F[DN], [RK], HExxH γ-proteobacteria, fusobacteria, firmicutes, planctomycetes T2SS, T6SS, T7SS (WXG,LDXD,LXG) - Repeats: RHS
Tox-MPTase5 metallopeptidase fold (α + β); HEELH Actinobacteria, γ-proteobacteria T2SS - Repeats: RHS
PVC-Metallopeptidase metallopeptidase fold (α + β); HExxH; Most versions of this domain are releasing peptidases in polymorphic toxins. However, some versions, often present at the C-terminal end of polymorphic toxins, are likely to additionally function as toxins Acidobacteria, actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chlorobi, chloroflexi, cyanobacteria, deinococci, firmicutes, nitrospirae, verrucomicrobia, archaea: euryarchaeota, eukaryotes: fungi(ascomycota) PVC - Proteases: PVC-Metallopeptidase; Repeats: RHS
Tox-MCF1-SHE All-α; S, T, HSxxE Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chlamydiae, viruses: Acanthamoeba polyphaga mimivirus T2SS, T7SS(WXG), PVC - Proteases: PVC-Metallopeptidase, Caspase, Tox-PLOTU
Tox-SerPeptidase α + β; H, R, R Actinobacteria, α,β,γ,δ,ϵ-proteobacteria T2SS, T7SS (WXG) - Proteases: Tox-PLOTU
Tox-YabG α + β; HxD, Y, E, [DE], GHD, Y, R Bacteroidetes, firmicutes PVC DUF1021(antitoxin in toxin-antitoxin systems), Imm-SUKH Proteases: PVC-Metallopeptidase
Tox-LD-peptidase LD-peptidase (PDB: 1ZAT); H, S, C Actinobacteria, bacteroidetes, β,γ,δ-proteobacteria, chloroflexi, firmicutes T2SS,T6SS, TcdB/TcaC Imm16, Imm57 Proteases: ZU5; Repeats: RHS
Tox-Caspase Caspase-like fold (α/β); H, C; Most versions of this domain are releasing peptidases in polymorphic toxins. However, some versions, often present at the C-terminal end of polymorphic toxins, are likely to additionally function as toxins Actinobacteria, α,β,γ,δ,ϵ-proteobacteria, bacteroidetes, chloroflexi, cyanobacteria, firmicutes, viruses: caudovirales T2SS,T6SS, T7SS (WXG,PPE), PVC Imm36 Proteases: PVC-Metallopeptidase; Repeats: RHS
Tox-HDC α + β; H, D, C β,γ-proteobacteria, viruses: caudovirales T2SS - Proteases: Caspase; Repeats: RHS
Tox-NLPC/P60 Papain-like peptidase fold (α + β); C, H, D Bacteroidetes, δ-proteobacteria T6SS, PVC, TcdB/TcaC - Proteases: PVC-Metallopeptidase, ZU5; Repeats: RHS
Tox-PL1 Papain-like peptidase fold (α + β); NC, H, D; Most versions of this domain are toxins in polymorphic toxins. However, some versions are, additionally, likely to be releasing peptidases Actinobacteria, bacteroidetes, γ,δ-proteobacteria, firmicutes, fusobacteria, gemmatimonadetes T2SS, T3SS, T6SS, T7SS (WXG), MuF - Proteases: Tox-Caspase, HINT; Repeats: RHS
Tox-PL-2 Papain-like peptidase fold (α + β); C, NxxH, DN β,δ-proteobacteria, cyanobacteria, firmicutes T2SS, TcdB/TcaC Imm73 Proteases: HINT, PLOTU, ZU5; Repeats: RHS
Tox-PL3 Papain-like peptidase fold (α + β); C, [DE]H, [DE], R Bacteroidetes, fibrobacteres, δ,ϵ-proteobacteria T2SS, TcdB/TcaC - Proteases: ZU5; Repeats: RHS
Tox-PLOTU Papain-like peptidase fold (α + β); C, H, D; Most versions of this domain are releasing peptidases in polymorphic toxins. However, some versions, often present at the C-terminal end of polymorphic toxins, are likely to additionally function as toxins Actinobacteria, α,γ-proteobacteria, bacteroidetes, chlamydiae, eukaryotes: fungi (ascomycota), metazoa, viridiplantae, viruses: Invertebrate iridescent virus 3, Wiseana iridescent virus T2SS (APD1), T7SS (WXG) - Repeats: Ankyrin, Sel1, FilH
Tox-PLC39 Papain-like peptidase fold (α + β); C, H, D Bacteroidetes, chloroflexi, firmicutes T2SS, T6SS, PVC - Proteases: PVC-Metallopeptidase; Repeats: RHS
Tox-PLDMTX Papain-like peptidase fold (α + β); C, W, H, D, Q α,β,γ-proteobacteria T2SS - -
Tox-TGase Papain-like fold (α + β); C, H, D β,γ,δ-proteobacteria, bacteroidetes, cyanobacteria T2SS, T3SS, PVC - Proteases: PVC-Metallopeptidase
Tox-UCH Papain-like fold (α + β) C, H, D β-proteobacteria PVC - Proteases: PVC-Metallopeptidase
Tox-OmpA α + β; α,β,γ-proteobacteria, cyanobacteria PVC - Proteases: PVC-Metallopeptidase
Protein-modifying toxins
Tox-ART-RSE; ADP-ribosyltransferase fold (α + β); RxDxR, S, [DN]xN, E Actinobacteria, α,β,γ,δ-proteobacteria, bacteroidetes, chloroflexi, firmicutes, planctomycetes, spirochaetes, tenericutes, eukaryotes: fungi (ascomycota, basidiomycota), metazoan (hexapoda, mollusca), viridiplantae, viruses: Vibrio phage CTX T2SS, T6SS, T7SS (WXG, LXG, LDXD) Imm41, Imm-ADP-RGHD (ADP-ribosyl glycohydrolase) Proteases: HINT, Caspase, MCF1-SHE Repeats: RHS, Tail-fiber
Tox-ART-PARP ADP-ribosyltransferase fold (α + β); HG[ST], Y, K, E Actinobacteria PVC - Proteases: PVC-Metallopeptidase
Tox-ART-HYE1 ADP-ribosyltransferase fold (α + β); H, Y, E γ-proteobacteria TcdB/TcaC? - Repeats: RHS
Tox-ART-HYD1 ADP-ribosyltransferase fold (α + β); H,[RK], [FY], [DE] Actinobacteria, β,γ-proteobacteria, bacteroidetes, firmicutes T2SS, T6SS, T7SS Imm-My6CBD; Proteases: HINT; Repeats: RHS
Tox-ART-HYD2 ADP-ribosyltransferase fold (α + β); H, D, GFY, W, R Actinobacteria, bacteroidetes, deinococci, fibrobacteres, firmicutes, fusobacteria, γ-proteobacteria, lentisphaerae, spirochaetes, synergistetes, eukaryotes: choanoflagellida, Capsaspora, fungi, cnidaria T2SS, PVC - Proteases: HINT, PVC-Metallopeptidase; Repeats: RHS, Tail-Fiber
Tox-ARC (ADP-Ribosyl cyclase) Flavodoxin fold (α/β); [ST] [DE], S, E Actinobacteria, bacteroidetes, cyanobacteria, firmicutes, β, γ- proteobacteria, spirochaetes eukaryotes: fungi (ascomycota, basidiomycota), Capsaspora , choanoflagellida, metazoa; This domain appears to have independently been acquired by the fungi and the animals from the bacteria. T2SS, T5SS, T6SS, T7SS (LXG, WXG) Imm74, Imm63; Imm74 is the primary immunity protein across wide phyletic range Repeats: RHS, FilH
Tox-Doc Doc/Fic fold (PDB: 2f6s, All-α); HxFx[DE]GNxR; (See Pfam PF02661) Actinobacteria, γ-proteobacteria T5SS, T7SS (WXG) Imm23, Imm-SUKH, Imm13 Proteases: Caspase; Repeats: FilH
Tox-CNF (Cytotoxic necrotizing factor) CNF1/YfiH fold (α + β, PDB: 1hzg); D, C, H; See Pfam PF05785 γ-proteobacteria T6SS - Repeats: RHS
Tox-Glycosyltransferase Nucleotide diphospho-sugar transferase fold (α/β); [DNE]xxR, YxDxD; See Pfam PF04488 Actinobacteria T7SS (WXG), PVC - Proteases: PVC-Metallopeptidase
Tox-Peptide Kinase α + β; DxH, YKP[KR], DxHxEN, DxE, S, R; Related to the kinase domain found in lantibiotic synthetases Firmicutes PVC - Proteases: PVC-Metallopeptidase
Pore-forming toxins
Tox-WTIP Two membrane spanning α-helices; RxxR, Wx[ST]IP α,β,γ-proteobacteria T2SS, PVC - Proteases: PVC-Metallopeptidase; Repeats: RHS
Toxins that act on carbohydrates
Tox-Aldo-ketoreductase Rossmann (α/β); Bacteroidetes, cyanobacteria PVC - Proteases: PVC-Metallopeptidases;
Tox-Glucosaminidase Lysozyme-like fold (α + β); E, N, Y (See Pfam PF01832) Firmicutes T6SS, PVC - Proteases: PVC-Metallopeptidase
Toxins that act on lipids
Tox-AB hydrolase1 (Pfam DUF2235) α/β hydrolase (α/β); DG, [ST]N, [KR], D, ExE, GxHxD Acidobacteria, actinobacteria, α,β,γ,δ,ϵ-proteobacteria, bacteroidetes, cyanobacteria, nitrospirae planctomycetes, verrucomicrobia, eukaryotes: fungi(ascomycota, basidiomycota), rhodophyta, viridiplantae T2SS, T6SS - Repeats: RHS
Tox- AB hydrolase3 α/β hydrolase (α/β); G[ST], GHSxG Actinobacteria, α,β,γ-proteobacteria, bacteroidetes, firmicutes T2SS, T6SS,T7SS (WXG), TcdB/TcaC Imm66, Imm69 Repeats: RHS, FilH
Tox-PLA2 Phospholipase A2 fold (All-α, PDB: 1kp4); DxC[ST], CxxHxxxYxN, C Actinobacteria, α,β,γ,δ-proteobacteria, aquificae, bacteroidetes, chlorobi, chloroflexi, cyanobacteria, deinococci, firmicutes, fusobacteria, nitrospirae, planctomycetes, spirochaetes, eukaryotes: fungi(ascomycota), heterolobosea, metazoa, stramenopiles, viridiplantae, Viruses: Campylobacter phage T2SS - Repeats: RHS, ALF
Tox-CDP-alcohol phosphatidyltransferase All-α; DxxDGxxxR, DxxxD; See Pfam PF01066 β-proteobacteria (mainly Neisseria species) PVC - Proteases: PVC-Metallopeptidase
Tox-Glycerophosphoryl diester phosphodiesterase (GDPD) TIM Barrel (PDB: 1VD6; α/β); HRG, E, ExD, D, H; See Pfam PF03009 Cyanothece sp. (Cyanobacteria) PVC - Proteases: PVC-Metallopeptidase
Miscellaneous toxins
Tox-AB hydrolase2 α/β hydrolase superfamily (α/β); NG, [DE], [KR], HSxG, D, H acidobacteria, α,β,γ,δ,ϵ-proteobacteria, chlamydiae, fusobacteria, verrucomicrobia, eukaryotes: fungi(ascomycota, basidiomycota), stramenopiles T2SS, T5SS, T6SS Imm-SUKH Repeats: FilH, RHS
Tox-ODYAM1 All-α; Several charged residues α-proteobacteria, bacteroidetes T2SS (APD1) - Proteases: Tox-PLOTU; Repeats: Sel1
Tox-LatrotoxinCTD Two conserved α-helices; D, [ST], Y, E α,γ-proteobacteria, eukaryotes: metazoa ( Latrodectus hasseltii, Latrodectus tredecimguttatus ) T2SS - Proteases: Tox-PLOTU; Repeats: ankyrin
Tox-SGS (salivary gland secreted protein) α + β; C, C, C, C, [DE}xx[ND] Eukaryotes: metazoan (crustacea, hexapoda) T2SS - Repeats: RHS
Ntox38 All-β; PXhhG and several hydrophobic residues Actinobacteria T2SS, T7SS (WXG) Imm56 Proteases: Mycosin (Subtilisin)-like protease in the neighborhood
Ntox46 α + β; [KR]STxxPxxDxx[ST], Q α,γ,δ-proteobacteria, bacteroidetes T2SS, T6SS - Repeats: RHS, FilH
  1. 1. Toxins are grouped and arranged based on the similarity of their known or predicted biochemical functions.
  2. 2. Where possible, known or predicted folds are described. The folds are further classified as All-α (composed entirely of α-helices), All-β (composed entirely of β-strands), α + β (Containing α-helices and β-strands) or α/β (comprising repeated α-helix-β-strand units) depending on the arrangement of their structural elements. Individual conserved residues and motifs are separated by commas. Alternative residues are enclosed in square brackets; ‘x’ denotes any residue, ‘h’ indicates a hydrophobic residue (LIYVFMCW).
  3. 3. By default most lineages are bacterial unless stated otherwise. Eukaryotes and viruses are shown in bold.
  4. 4. T2SS: Type 2 secretion system; T5SS: Type 5 secretion system, T6SS: Type 6 secretion system, T7SS: Type 7 secretion system. The secretory domains for T7SS are shown next to it in parentheses.