Molecular Basis for the Heterogeneity of Human Tyrosinase

A cDNA clone, pHTγ1, 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, pHTγ1 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 a 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.