Molecular basis for the heterogeneity of human tyrosinase.

A cDNA clone, pHT gamma 1, representing human tyrosinase mRNA was isolated by screening a melanoma cDNA library with a synthetic oligonucleotide complementary to a segment of the human tyrosinase cDNA, Pmel 34 [Kwon et al. (1987) Proc. nat. Acad. Sci. USA 84, 7473-7477]. However, there are a number of differences in the nucleotide sequence between two cDNAs, pHT gamma 1 and Pmel 34, particularly in the region coding for the carboxyl terminus of the enzyme (putative exon 5). We therefore cloned the genomic DNA segment carrying the exon 5 of the human tyrosinase gene by screening a human placental genomic DNA library with a cloned cDNA probe. The nucleotide sequences of human tyrosinase cDNA as well as part of its gene were determined. Mature human tyrosinase is composed of 511 amino acids with a molecular weight of 58,000. We provide evidence for the presence of at least two species of human tyrosinase mRNA generated by alternative splicing in human pigmented melanoma cells.