Fire corals (Millepora spp.) cause severe pain and inflammatory effects in humans upon contact, and the organs responsible for these effects are called nematocysts. Here, we isolated an active cytotoxin of ca. 18 kDa (MCTx-1) from nematocysts of Millepora dichotoma var. tenera. MCTx-1 was potently cytotoxic (EC50 value 79 ng/mL) towards L 1210 mouse leukemia cells, hemagglutinated a 0.8% suspension of sheep erythrocytes (0.2 mu g protein/mL) and was lethal in crayfish (LD50, 106 mu g/kg). We deduced the primary structure of MCTx-1 from the corresponding cDNA sequence and found that MCTx-1 is a novel dermatopontin that is an extracellular matrix protein in mammals. This is the first characterization of a proteinaceous toxin from fire coral. (c) 2007 Elsevier Inc. All rights reserved.