Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium.

The retinal pigment epithelium (RPE) of the eye expresses an abundant 61 kDa protein (RPE65), that is developmentally regulated and tissue-specific. In our efforts toward understanding the specialized functions and development of the RPE, and the origins of inherited retinal degenerations, we have characterized the human gene encoding the 61 kDa protein. This is the first structural characterization of a gene transcribed specifically in the RPE. The gene maps to human chromosome 1p31. The sequence encoding the transcript spans over 20 kb, and is interrupted by 13 introns. A putative transcription start site lies 54 bp upstream of the initiation codon. A single transcript of approximately 2.9 kb is present in human RPE, and is not detected in other tissues. The deduced 533 amino acid sequence of the human protein is 98.7% identical to the bovine, but shows no significant similarity to any other entry in the databases. Expression of the 61 kDa protein appears to depend on the presence of environmental cues, since the corresponding transcripts are rapidly lost from RPE cells established in culture. Down regulation may occur post-transcriptionally, since AU-rich elements proposed to target RNA for rapid degradation are present throughout the 3'-untranslated region. The tissue-specific expression, high abundance, evolutionary conservation, developmental regulation, and sequence of the 3'-untranslated region suggest that the 61 kDa protein is the product of a functionally important gene whose expression is tightly regulated.