TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.C.11.1.1









Leukotoxin, HlaA

Bacteria
Proteobacteria
HlaA of Mannheimia (Pasteurella) haemolytica
*1.C.11.1.2









RTX-toxin IIA; haemolysin IIA; cytolysin IIA, ClyIIA
Bacteria
Proteobacteria
ClyIIA of Actinobacillus pleuropneumoniae
*1.C.11.1.3









Haemolysin A, HlyA (α-haemolysin) (Wiles and Mulvey 2013). The channel-forming domain may contain β-strands, possibly in addition to alpha-helical structures (Benz et al. 2014).  Although homologous, HlyA and CyaA (1.C.11.1.4) exhibit different modes of permeabilization (Fiser and Konopásek 2009). HlyA triggered an increase in mitochondrial Ca2+ levels and manipulated mitochondrial dynamics by causing fragmentation of the mitochondrial network. Alterations in mitochondrial dynamics resulted in severe impairment of mitochondrial functions by loss of membrane potential, increase in reactive oxygen species production, and ATP depletion. HlyA also caused disruption of plasma membrane integrity (Lu et al. 2018).

Bacteria
Proteobacteria
HlyA of E. coli
*1.C.11.1.4









Bifunctional adenylate cyclase-haemolysin toxin precursor, CyaA.  Although homologous, HlyA (1.C.11.1.3) and CyaA  exhibit different modes of permeabilization (Fiser and Konopásek 2009).  A pore model comprising three alpha2-loop-alpha3 hairpins suggested that Gly530XXGly533XXXGly537  in TMS2 could function in toxin oligomerization (Juntapremjit et al. 2015).  Structural integrity of TMSs 1, 2, 3 and 5, but not 4, is important for haemolytic activity, particularly for transmembrane helices 2 and 3 that might form the pore (Powthongchin and Angsuthanasombat 2009). CyaA forms small cation-selective membrane pores that permeabilize cells for potassium efflux, contributing to cytotoxicity of CyaA and eventually provoking colloid-osmotic cell lysis (Wald et al. 2016).  The toxin penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into the cytosol its N-terminal adenylate cyclase enzyme domain (~400 residues). In parallel, the ~1300 residue-long RTX hemolysin moiety of CyaA permeabilizes target cell membranes for efflux of cytosolic potassium ions (Svedova et al. 2016).  Positively-charged side-chains substituted at positions Gln574 and Glu581 in the pore-lining alpha3 enhance hemolytic activity and ion-channel opening, mimicing the highly-active RTX (repeat-in-toxin) cytolysins (Kurehong et al. 2017). Residues 529 to 549 participate in membrane penetration and pore-forming activity (Roderova et al. 2019).

Bacteria
Proteobacteria
CyaA of Bordetella pertussis
*1.C.11.1.5









Cytolytic RTX-toxin, GtxA (causes salpingitis and peritonitis in birds (Kristensen et al., 2009)

Bacteria
Proteobacteria
GtxA of Gallibacterium anatis
*1.C.11.1.6









Enterohemolysin EhxA of 998 aas

Bacteria
Proteobacteria
EhxA of E. coli
*1.C.11.1.7









Leukotoxin A, LtxA pore-forming toxin of 1055 aas, exhibiting β-hemolytic activity.  Plays a role in immune evasion by lysing human lymphocytes and monocytes. It binds to the LFA-1 integrin on the surface of the host cell and to cholesterol-containing membranes, resulting in large LtxA-LFA-1 clusters in lipid rafts (Balashova et al. 2006; Brown et al. 2013).  Blocking P2X receptors protects monocytes from LtxA (Fagerberg et al. 2016).

Bacteria
Proteobacteria
LtxA of Aggregatibacter (Actinobacillus) actinomycetemcomitans (Haemophilus actinomycetemcomitans)
*1.C.11.1.8









Leukotoxin, RtxA or IktA, of 956 aas.

Bacteria
Proteobacteria
RtxA if Kingella kingae