A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase

Katsuhiko Tsukamoto, Ian Jackson, Kazunori Urabe, Paul M Montague, Vincent J Hearing

Research output: Contribution to journalArticlepeer-review

Abstract

The production of melanin pigment in mammals requires tyrosinase, an enzyme which hydroxylates the amino acid tyrosine to DOPA (3,4-dihydroxyphenylalanine), thus allowing the cascade of reactions necessary to synthesize that biopolymer. However, there are other regulatory steps that follow the action of tyrosinase and modulate the quantity and quality of the melanin produced. DOPAchrome tautomerase is one such melanogenic enzyme that isomerizes the pigmented intermediate DOPAchrome to DHICA (5,6-dihydroxyindole-2-carboxylic acid) rather than to DHI (5,6-dihydroxyindole), which would be generated spontaneously. This enzyme thus regulates a switch that controls the proportion of carboxylated subunits in the melanin biopolymer. Efforts to clone the gene for tyrosinase have resulted in the isolation of a family of tyrosinase related genes which have significant homology and encode proteins with similar predicted structural characteristics. Using specific antibodies generated against synthetic peptides encoded by unique areas of several of those proteins, we have immuno-affinity purified them and studied their melanogenic catalytic functions. We now report that TRP-2 (tyrosinase related protein-2), which maps to and is mutated at the slaty locus in mice, encodes a protein with DOPAchrome tautomerase activity.
Original languageEnglish
Pages (from-to)519-26
Number of pages8
JournalEMBO Journal
Volume11
Issue number2
Publication statusPublished - Feb 1992

Keywords

  • Amino Acid Sequence
  • Animals
  • Antibodies
  • Chromatography, Affinity
  • Dihydroxyphenylalanine/metabolism
  • Female
  • Intramolecular Oxidoreductases
  • Isomerases/isolation & purification
  • Isomerases/metabolism
  • Kinetics
  • Melanins/biosynthesis
  • Melanocytes/enzymology
  • Melanoma, Experimental/enzymology
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Molecular Sequence Data
  • Monophenol Monooxygenase/metabolism
  • Peptides/chemical synthesis
  • Peptides/immunology
  • Tumor Cells, Cultured

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