A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus.
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.
Jackson
I J
IJ
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Chambers
D M
DM
Tsukamoto
K
K
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Hearing
V
V
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004815:Epidermal Growth Factor / Q000235:genetics; D005260:Female; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009115:Muridae; D009154:Mutation; D010088:Oxidoreductases; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D004247:DNA; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase