A cDNA clone encoding a transglutaminase (TGase) was isolated from a cDNA library prepared from the larval stage of Ciona intestinalis. The cDNA sequence has an open reading frame encoding a protein of 696 amino acids and is about 36% identical to 11 other TGase sequences. In addition, the critical residues thought to form the catalytic center are conserved. The Ciona TGase (CiTGase) has an extension of 39 amino acids in the NH2-terminal region similar to that reported for keratinocyte TGases. A phylogenetic analysis among other types of TGases demonstrated that CiTGase represents a new type of the enzyme.