Major toxin belonging to the bicyclic octapeptides amatoxins that acts by binding non-competitively to RNA polymerase II and greatly slowing the elongation of transcripts from target promoters (PubMed:4865716, PubMed:363352, PubMed:7642577, PubMed:8702941). Processed by the macrocyclase-peptidase enzyme POPB to yield a toxic cyclic decapeptide (PubMed:24613547). POPB first removes 10 residues from the N-terminus (By similarity). Conformational trapping of the remaining peptide forces the enzyme to release this intermediate rather than proceed to macrocyclization (By similarity). The enzyme rebinds the remaining peptide in a different conformation and catalyzes macrocyclization of the N-terminal 8 residues (By similarity). LD(50) is 0.35 mg/kg by intraperitoneal injection into mice (PubMed:363352). LD(50) is 4 mg/kg by intravenous injection into rats, and 0.1 mg/kg by intravenous injection into dogs (PubMed:363352). LD(50) is 2 ug/kg by intracerebroventricular injection into mice, and 10 ug/kg by intracerebroventricular injection into rats (PubMed:363352). The typical symptoms of amatoxin poisoning are gastro-intestinal distress beginning 6-12 h after ingestion, a remission phase lasting 12-24 h, and progressive loss of liver function culminating in death within 3-5 days (PubMed:12475187). One of the few effective treatments is liver transplantation (PubMed:12475187). Belongs to the MSDIN fungal toxin family. This peptide is cyclic. The peptide order is assigned by homology with the gene sequence for alpha-amanitin from Amanita bisporigera. In peptide sequencing work prior to 1968, the residue shown in the first position was reported as a beta-methylleucine derivative that could arise by either beta-methylation of leucine or gamma-methylation of isoleucine. The correct structure has been determined to be derived from isoleucine without methylation.