Precursor of a multifunctional toxin that causes destruction of the actin cytoskeleton by covalent cross-linking of actin and inactivation of Rho GTPases when translocated into the host cytoplasm (PubMed:26185092). Upon translocation into the host cell, undergoes autoprocessing in cis mediated by the peptidase C80 domain (also named CPD domain): the protease activity is activated upon binding inositol hexakisphosphate (InsP6) present at the host cell membrane and delivers the Cysteine protease domain-containing toxin F3 chain to the host cytosol (PubMed:17464284, PubMed:18591243, PubMed:18845756, PubMed:19620709, PubMed:19465933). The Cysteine protease domain-containing toxin F3 chain will then further cleave and release effector toxin chains that cause disassembly of the actin cytoskeleton and enhance V.cholerae colonization of the small intestine, possibly by facilitating evasion of phagocytic cells (PubMed:11553575, PubMed:12045243, PubMed:17698573, PubMed:17698571, PubMed:19812690, PubMed:19620709). Following autocatalytic cleavage in cis at the Leu-3441-Ala-3442 site, this chain mediates processing in trans to release other individual toxin chains to the host cytosol (PubMed:19620709). Released effector toxin chains cause disassembly of the actin cytoskeleton and enhance V.cholerae colonization of the small intestine, possibly by facilitating evasion of phagocytic cells (PubMed:17698573, PubMed:17698571). Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin (PubMed:11032799, PubMed:15199181, PubMed:16954226, PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200, PubMed:26228148). Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits (PubMed:23029200). Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin (PubMed:11032799, PubMed:15199181, PubMed:16954226, PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200, PubMed:26228148). Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits (PubMed:23029200). N-epsilon-fatty acyltransferase that mediates lysine-palmitoylation of host Rho GTPase proteins, with a strong preference for host Rac1 (PubMed:29074776). After delivery to the host cytosol, localizes to the host cell membrane where it palmitoylates host Rho GTPase proteins, resulting in loss of all active GTP-bound Rho and subsequent actin depolymerization (PubMed:17474905, PubMed:19434753, PubMed:23184949, PubMed:29074776). Prenylation of host Rac1 at the C-terminus is required for lysine-palmitoylation (PubMed:29074776). Indirectly activates the small GTPase CDC42. hexadecanoyl-CoA + L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein] = CoA + H(+) + N(6)-hexadecanoyl-L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein] dodecanoyl-CoA + L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein] = CoA + H(+) + N(6)-dodecanoyl-L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein] decanoyl-CoA + L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein] = CoA + H(+) + N(6)-decanoyl-L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein] Binds 2 Mg(2+) ions per subunit. Mg(2+) is required for actin cross-linking activity. Can also use Mn(2+) ions instead of Mg(2+). Protease activity is inhibited by N-ethylmaleimide but not other protease inhibitors (PubMed:17464284). Protease activity is inhibited by aza-leucine epoxide (PubMed:19465933). Protease activity is activated upon binding inositol hexakisphosphate (InsP6) via an allosteric mechanism: the active site is disordered or occluded in the absence of InsP6, protecting the protease active-site sulfhydryl until the toxin enters a eukaryotic cell (PubMed:18845756, PubMed:19620709). Upon processing at the Leu-3441-Ala-3442 site, the peptidase C80 domain is converted to a form with much reduced affinity for InsP6, but is reactivated for high affinity binding of InsP6 by cooperative binding of both a new substrate and InsP6. Reactivation allows cleavage at other sites, specifically at Leu residues between the effector domains (PubMed:19620709). Optimum pH is 7.0-9.0. Secreted via the type I secretion system. Targeted to the host cell membrane via the membrane localization region (MLD). Truncated N-terminus.