We have identified and characterized a cDNA from the brain tissue of the highly commercial marine fish species, the gilthead sea bream (Sparus aurata), which encodes a 496 amino acid residue protein sharing the organizational and structural features of the mammalian prion proteins. Tissue mRNA expression analyses revealed the presence of this transcript in various tissues of the gilthead sea bream including the brain, the spleen, and the heart. Sequence comparison and phylogenetic analysis showed the gilthead sea bream protein to be the homologue of one of the long form prion proteins identified from the model fish species Takifugu rubripes and Danio rerio. Unique to this fish prion protein is an extended Gly-Tyr-Pro-rich region, a structural feature that apparently resulted from multiple duplications of a core motif. The presence of this feature in other seemingly unrelated proteins suggests the involvement of common mechanism(s) in its formation and infers possible evolutionary trends related to its function.