Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis

EMBO J. 1994 Dec 15;13(24):5818-25.

Abstract

Several genes critical to the enzymatic regulation of melanin production in mammals have recently been cloned and mapped to the albino, brown and slaty loci in mice. All three genes encode proteins with similar structures and features, but with distinct catalytic capacities; the functions of two of those gene products have previously been identified. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, while the slaty locus encodes tyrosinase-related protein 2 (TRP2), an enzyme with a single specific, but distinct, function as DOPAchrome tautomerase. Although the brown locus, encoding TRP1, was actually the first member of the tyrosinase gene family to be cloned, its catalytic function (which results in the production of black rather than brown melanin) has been in general dispute. In this study we have used two different techniques (expression of TRP1 in transfected fibroblasts and immunoaffinity purification of TRP1 from melanocytes) to examine the enzymatic function(s) of TRP1. The data demonstrate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indole-quinone at a down-stream point in the melanin biosynthetic pathway. This enzyme activity appears to be essential to the further metabolism of DHICA to a high molecular weight pigmented biopolymer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell-Free System
  • Chromatography, Affinity
  • Indoles / metabolism*
  • Melanins / biosynthesis*
  • Melanocytes / metabolism
  • Melanoma / metabolism
  • Membrane Glycoproteins*
  • Mice
  • Monophenol Monooxygenase*
  • Oxidation-Reduction
  • Oxidoreductases*
  • Proteins / genetics
  • Proteins / isolation & purification
  • Proteins / metabolism*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Indoles
  • Melanins
  • Membrane Glycoproteins
  • Proteins
  • Recombinant Proteins
  • 5,6-dihydroxy-2-indolylcarboxylic acid
  • Oxidoreductases
  • Tyrp1 protein, mouse
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase
  • 5,6-dihydroxyindole