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

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.

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

“…TYRP2, also known as L-DOPAchrome tautomerase, is an enzyme that has been well characterized for its function in non-decarboxylative tautomerization of L-DOPAchrome to the highly stable product 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the melanin biosynthetic pathway in melanocytes (Leonard et al, 1988;Aroca et al, 1990;Pawelek, 1990;Tsukamoto et al, 1992;Jackson et al, 1992). TYRP2, along with the enzymes tyrosinase and TRYP1, comprise the tyrosinase family of proteins, and Figure 6 TYRP2 is not expressed in a panel of non-melanoma human cancer cell lines.…”

Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins

“…Whether in vivo TYRP1 can also incorporate copper ions is not known.W hich factorsd etermine whether zinc or copperi ons are incorporated in the native human melanogenic enzymes remains unclear.I nterestingly,T YRP2 also contains zinc ions in the active site [28] and displaysd opachrome tautomerase activity. [29] However,d opachrome tautomerase activity hasn ot yet been confirmed or disproved for TYRP1.I tc annot even be ruled out that this latter reactioncan occur without enzyme. [30] Interestingly,T YRP1 binds typical tyrosinase substrates and inhibitors (tyrosine, mimosine,k ojic acid, and tropolone), as shownbyc rystal structures.…”

“…[29] Based on the similarity of TYRP2 to tyrosinases, dopachrome was proposed to bind to the zinc ions in ab identate way,w ith its two hydroxyl groups binding to different zinc ions, each displacing aw ater molecule. [10] An electronic rearrangementi n the indole ring then leads to the formation of DHICA as the product (Figure 4).…”

Identification of Drosophila melanogaster yellow-f and yellow-f2 proteins as dopachrome-conversion enzymes

“…Recently we isolated a DCE cDNA (AaDce1) from a mosquito (Aedes aegypti) pupal library [7], and subsequently evaluated its chemical characteristics [8]. The amino acid sequence of the A. aegypti DCE shares no similarity to those of mammalian dopachrome tautomerase, which uses the same substrate (although their products are different, see Scheme 1) and is involved in the same melanization pathway [9][10][11][12][13][14][15]. However, the AaDce1 primary sequence is 16-40 % similar to the Drosophila yellow proteins (see Figure 1).…”