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Amelogenins are the major proteins involved in tooth enamel formation. In the present study, we have cloned and sequenced four novel amelogenins from three amphibian species in order to analyze similarities and differences between mammalian and non-mammalian amelogenins. The newly sequenced amphibian amelogenin sequences were from a red-eyed tree frog (Litoria chloris) and a Mexican axolotl (Ambystoma mexicanum). We identified two amelogenin isoforms in the Eastern red-backed salamander (Plethodon cinereus). Sequence comparisons confirmed that non-mammalian amelo-genins are overall shorter than their mammalian counterparts, contain less proline and less glutamine, and feature shorter polyproline tripeptide repeat stretches than mammalian amelogenins. We propose that unique sequence parameters of mammalian amelogenins might be a pre-requisite for complex mammalian …