Heterodimer CA-CB: Crotoxin is a potent presynaptic neurotoxin that possesses phospholipase A2 (PLA2) activity and exerts a lethal action by blocking neuromuscular transmission (By similarity). It consists of a non-covalent association of a basic and weakly toxic PLA2 subunit (CBa2, CBb, CBc, or CBd), with a small acidic, non-enzymatic and non-toxic subunit (CA1, CA2, CA3 or CA4) (By similarity). The complex acts by binding to a specific 48-kDa protein (R48) receptor located on presynaptic membranes, forming a transient ternary complex CA-CB-R48, followed by dissociation of the CA-CB complex and release of the CA subunit (By similarity). At equilibrium, only the CB subunits remain associated with the specific crotoxin receptor (By similarity). In addition to neurotoxicity, crotoxin has been found to exert myotoxicity, nephrotoxicity, and cardiovascular toxicity (PubMed:20109480). Moreover, anti-inflammatory, immunomodulatory, anti-tumor and analgesic effects of crotoxin have also been reported (PubMed:20109480). Monomer CBc: The basic subunit of crotoxin is a snake venom phospholipase A2 (PLA2) that exhibits weak neurotoxicity (10-fold less than the heterodimer) and very strong anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 0.7 nM) (PubMed:18062812). In addition, it shows the same effects described for the heterodimer and binds the nucleotide-binding domain (NBD1) of CFTR chloride channels and increases the channel current (PubMed:27241308). PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) Binds 1 Ca(2+) ion. Heterodimer of one of the acidic (CA1, CA2, CA3 or CA4) and one of the basic (CBa1, CBa2, CBb, CBc or CBd) subunits; non-covalently linked. The acidic subunit is non-toxic, without enzymatic activity and comprises 3 peptides that are cross-linked by 5 disulfide bridges. The basic subunit is toxic, has phospholipase A2 activity and is composed of a single chain. Multiple variants of each subunit give different crotoxin complexes that can be subdivided into 2 classes: (1) those of high toxicity, low PLA2 activity (CBb, CBc and CBd linked with high affinity to any CA) and high stability (K(d)=4.5 nM) and (2) those of moderate toxicity, high PLA2 activity (CBa2 linked with low affinity to any CA) and low stability (K(d)=25 nM). Interacts with human NBD1 domain of CFTR (PubMed:27241308). Expressed by the venom gland. In monomer CBc, LD(50) is 480 ug/kg by intravenous injection into mice. In class 1 heterodimer CA2-CBc, LD(50) is 80 ug/kg by intravenous injection into mice. In class 1 heterodimer CA3-CBc, LD(50) is 110 ug/kg by intravenous injection into mice. Crotoxin (CA-CBc) is under phase I clinical trial as an anti-tumor drug. It has been shown to induce neurotoxic tolerance in animals allowing them to receive high doses associated with effective anti-tumor activity in the absence of adverse side effects. May be used to develop new agents to treat the most common mutation of cystic fibrosis (PHE-508 DEL). It shows a double function: (i) as a potentiator, by increasing the chloride channel current, and (ii) as a corrector, by permitting PHE-508 DEL to escape from the degradation pathway, facilitating its biosynthesis and subsequent delivery to the plasma membrane. The crotoxin heterodimer is inhibited by the crotoxin inhibitor from Crotalus serum (CICS). CICS neutralizes the lethal potency of crotoxin and inhibits its PLA2 activity. CICS only binds tightly to the CB subunit and induces the dissociation of the heterodimer (By similarity). Tested on the CA2-CBd heterodimer (PubMed:10903514). Belongs to the phospholipase A2 family. Group II subfamily. D49 sub-subfamily.