Cationic peptide that possesses multiple functions. It acts as a cell-penetrating peptide (CPP), and as a potent voltage-gated potassium channel inhibitor. It exhibits antimicrobial activities, hind limb paralysis, and severe muscle necrosis by a non-enzymatic mechanism. As a cell-penetrating peptide, crotamine has high specificity for actively proliferating cells, and interacts inside the cell with subcellular and subnuclear structures, like vesicular compartments, chromosomes and centrioles. It penetrates into the cells as fast as five minutes after its addition to cell culture medium (PubMed:18662711). In vivo, after intraperitoneal administration, it is found in cells of peritoneal fluid and bone marrow, demonstrating preferential nuclear and perinuclear localization. To enter the cell, it interacts with the chains of heparan sulfate membrane proteoglycan (HSPG), and is endocytosed (in complex with HSPG) in vesicles which are transported into the cell with the help of clathrin. Inside the cell, crotamine accumulates in lysosomal vesicles. As soon as the peptide accumulates in endosomes/lysosomes vesicles, these compartments are disrupted and their contents released into the cytosol. This loss of lysosomal content induces cell death at high concentrations, or promotes the distribution of crotamine in cytoplasmic compartments, which is a step before crotamine nuclear uptake (PubMed:15231729, PubMed:17491023). As a potassium channel inhibitor, this toxin selectively inhibits Kv1.1/KCNA1, Kv1.2/KCNA2 and Kv1.3/KCNA3 channels with an IC(50) of 369, 386 and 287 nM, respectively (PubMed:22498659). The inhibition of Kv1.3/KCNA channels induced by this toxin occurs rapidly and is voltage-independent. The channel inhibition is reversible after washing, suggesting a pure and classical channel blockage effect, without effects in potassium channel kinetics (PubMed:22498659). As an antimicrobial peptide, crotamine shows antibacterial activity against E.coli and B.subtilis, and antifungal activity against Candida spp., Trichosporon spp. and C.neoformans. It kills bacteria through membrane permeabilization. Monomer. Expressed by the venom gland. LD(50) is 1.5 mg/kg by intravenous injection. LD(50) is 32.8 mg/kg by intraperitoneal injection into mice. Has high potential for use as an anticancer agent. In vivo treatment with this protein significantly delays tumor implantation, inhibits tumor growth and prolongs the lifespan of the mice with melanoma tumors. It has also potent and specific toxicity against tumor cell lines of aggressive mouse and human tumors, but low cytotoxicity against non-tumoral cell lines. In addition, this protein can act as a carrier capable of delivering DNA into replicating cells with low cytotoxicity against normal proliferative cells (PubMed:21062230, PubMed:22142367, and PubMed:21834748). Has no hemolytic activity (PubMed:21386851, PubMed:23022146). Has low harmful effects on normal mammal cells. Does not show activity against the filamentous fungi A.fumigatus and T.rubrum at concentrations up to 125 ug/mL (PubMed:23022146). Does not directly affect voltage-gated sodium channels Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A and Nav1.6/SCN8A (PubMed:17588630). Belongs to the crotamine-myotoxin family. The analgesic activity produced by crotamine in Mancin et al., 1998 may be a misinterpretation (PubMed:9839677). This activity is probably due to the co-elution with the 14 amino acids crotalphine peptide (AC P08878). In that article crotamine was purified uniquely by gel filtration G-75. This single chromatographic step without going through a RP-HPLC is not sufficient to separate crotamine from other low molecular weight peptides such as the potent analgesic crotalphine peptide. Studies have shown that crotamine is present in the venom of certain specimens of C.durissus terrificus, and absent in others. This is due to geographical variations (PubMed:10484745).