A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus

Ian Jackson, D M Chambers, Katsuhiko Tsukamoto, Neal G Copeland, Debra J Gilbert, Nancy A Jenkins, Vincent Hearing

Research output: Contribution to journalArticlepeer-review

Abstract

We have cloned and sequenced mouse cDNAs corresponding to a third member of a family of melanocyte-specific mRNAs, which encode tyrosinase and related proteins. This new member, tyrosinase-related protein-2 (TRP-2), has approximately 40% amino acid identity with the two other proteins in the family and has the same structural features including two copper binding sites, two cysteine-rich regions, a signal peptide and a transmembrane domain. We now show that one of the cysteine-rich regions in this protein family is an 'EGF-like' repeat found in many extracellular and cell surface proteins. The gene encoding TRP-2 maps to mouse chromosome 14, in the region of the coat colour mutation slaty. We show that the TRP-2 of slaty mice has a single amino acid difference from wild-type TRP-2; a substitution of glutamine for arginine in the first copper binding site. TRP-2 is the much sought melanogenic enzyme DOPAchrome tautomerase (DT), which catalyses the conversion of DOPAchrome to 5,6,dihydroxyindole-2-carboxylic acid. Extracts from mice homozygous for the slaty mutation have a 3-fold or more reduction in DT activity, indicating that TRP-2/DT is encoded at the slaty locus, and the missense mutation reduces but does not abolish the enzyme activity.
Original languageEnglish
Pages (from-to)527-35
Number of pages9
JournalEMBO Journal
Volume11
Issue number2
Publication statusPublished - Feb 1992

Keywords

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Crosses, Genetic
  • DNA/genetics
  • DNA/isolation & purification
  • Epidermal Growth Factor/genetics
  • Female
  • Intramolecular Oxidoreductases
  • Isomerases/genetics
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Monophenol Monooxygenase/genetics
  • Muridae
  • Mutation
  • Oxidoreductases
  • Polymerase Chain Reaction
  • Proteins/genetics
  • RNA, Messenger/genetics
  • Sequence Homology, Nucleic Acid

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