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).

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).

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)