Article

Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus published erratum appears in Proc. nat. Acad. Sci. (Wash.) 1988 Sep; 85(17)

Yale University, New Haven, Connecticut, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/1987; 84(21):7473-7. DOI: 10.1073/pnas.84.21.7473
Source: PubMed

ABSTRACT Screening of a lambda gt11 human melanocyte cDNA library with antibodies against hamster tyrosinase (monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1) resulted in the isolation of 16 clones. The cDNA inserts from 13 of the 16 clones cross-hybridized with each other, indicating that they were from related mRNA species. One of the cDNA clones, Pmel34, detected one mRNA species with an approximate length of 2.4 kilobases that was expressed preferentially in normal and malignant melanocytes but not in other cell types. The amino acid sequence deduced from the nucleotide sequence showed that the putative human tyrosinase is composed of 548 amino acids with a molecular weight of 62,610. The deduced protein contains glycosylation sites and histidine-rich sites that could be used for copper binding. Southern blot analysis of DNA derived from newborn mice carrying lethal albino deletion mutations revealed that Pmel34 maps near or at the c-albino locus, the position of the structural gene for tyrosinase.

Download full-text

Full-text

Available from: Seymour Pomerantz, Aug 19, 2015
0 Followers
 · 
133 Views
  • Source
    • "Apart from the CuA and CuB His-based regions the structure of all mammalian tyrosinases also comprises of the N-terminal signal peptide, which is vital for intracellular trafficking and processing, the cysteinerich domains, the C-terminal hydrophobic trans-membrane segment and a short cytoplasmic tail (Kwon et al., 1987; Shibahara et al., 1988; Kwon, 1993; Garcia-Borron and Solano, 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: L-Tyrosinase (E.C. 1.14.18.1) is a member of type 3 copper enzyme family and is found throughout the phylogenetic scale of living organisms. It catalyzes the hydroxylation of monophenols to ortho-diphenols (cresolase activity), oxidation of o-diphenols to o-quinones (catecholase activity). The enzyme is involved in a number of important biological processes such as biosynthesis of phenol polymers for instance flavonoids and tannins, defense responses in plants and fungi, enzymatic browning as observed in horticultural produce and scale formation of insect cuticle. Besides, L-tyrosinase can also be utilized for the commercial production of L-DOPA, for the removal of phenolic compounds from wastewater, to detect phenolic pollutants in industrial effluents, food products etc. Tyrosinases from various organisms including bacteria, fungi, plants and mammals have been compared with respect to their tertiary structure, domain structure, Cu binding sites and activation mechanism. Although numerous information about the structural and molecular features of L-tyrosinase have been revealed, more efforts in this direction will enable to develop processes for utilizing the enzyme in a variety of fields.
    Biotechnology Volume 5: Gene and Protein Engineering, Edited by Jitendra K Thakur, 01/2014: chapter L-Tyrosinase - A Multifunctional Enzyme: Structural and Molecular Features: pages 425-445; Studium Press LLC., ISBN: 9781626990203
  • Source
    • "Despite the early role of the rabbit in defining genetic mechanisms determining this phenotypic trait, only recently a few loci have been characterized at the molecular level analysing also in rabbits (Aigner et al. 2000, Fontanesi et al. 2006, 2010a, 2010b) genes already shown to affect coat colour in mice (Kwon et al. 1987, Bultman et al. 1992, Robbins et al. 1993). Among these loci, agouti and extension control the production and relative amount of eumelanin (black/brown pigments) and pheomelanin (red/yellow pigments). "
    [Show abstract] [Hide abstract]
    ABSTRACT: After the rediscovery of the Mendel's laws, the domesticated European rabbit (Orycolagus cuniculus) has been the objective of pioneering studies on coat colour genetics. However, despite the early role of this species in defining genetic mechanisms determining this phenotypic trait, only recently a few loci have been characterized at the molecular level analysing also in rabbits genes already shown to affect coat colour in mice. We herein investigated the rabbit premelanosome protein (PMEL) gene, also known as melanocyte protein Pmel 17 (PMEL17) or silver (SILV), as mutations in the homologous gene in mice and other species produce phenotypic effects similar to what is observed in the dilute coat colour in rabbit. The rabbit dilute locus is determined by a recessive coat colour mutation that dilutes the black to blue (grey) interacting with the basic colours influenced by the agouti and extension loci. To investigate this candidate gene, we isolated and sequenced cDNAs as well as portions of intronic and exonic regions of the PMEL gene in several rabbits with different coat colours and identified single nucleotide polymorphisms, including several missense mutations. One polymorphism, positioned in intron 7, was genotyped in a family in which there was segregation of the dilute coat colour. The results excluded PMEL as the causative gene for the dilute locus in rabbits, shortening the list of candidate genes that should be analysed to identify the mutation determining this phenotypic trait.
    Archiv fur Tierzucht 02/2013; 56:42-49. DOI:10.7482/0003-9438-56-005 · 0.33 Impact Factor
  • Source
    • "Mushroom TYR is often used as a substitute for human TYR in order to screen TYR inhibitors because the former is commercially available in a purifi ed form (Briganti et al., 2003; Parvez et al., 2007). The use of mushroom TYR for this purpose, however, can be problematic because it is quite different from human TYR in terms of the amino acid sequence (Lerch, 1978; Kwon et al., 1987; Klabunde et al., 1998). Therefore, in the "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tyrosinase (TYR) catalyzes rate-limiting steps of melanogenesis and thus its inhibitors are potentially useful as hypopigmenting agents. Recently, p-coumaric acid (p-CA) has been suggested to interfere with the pro-melanogenic actions of tyrosine due to its structural similarity with tyrosine (An SM et al., Br J Dermatol 2008. 159: 292). In this study, we compared the inhibitory effects of p-CA and two other well known TYR inhibitors used in cosmetics--arbutin and kojic acid--on the catalytic activities of mushroom, murine and human TYRs in vitro, using tyrosine and 3,4-dihydroxyphenylalanine (DOPA) as substrates. The results showed that p-CA is a weaker inhibitor of mushroom TYR but much stronger inhibitor of human or murine TYR in comparison with kojic acid and arbutin. In addition, p-CA inhibited human TYR at much lower concentrations than those required for the inhibition of murine or mushroom TYRs. Enzyme kinetics analysis indicated that p-CA is a mixed type (for tyrosine) or competitive inhibitor (for DOPA) of human TYR. Potent antimelanogenic effects of p-CA were observed in human epidermal melanocytes exposed to UVB. The present study demonstrated that p-CA is a potent and selective inhibitor of human TYR and is potentially useful as a hypopigmenting agent.
    Phytotherapy Research 08/2010; 24(8):1175-80. DOI:10.1002/ptr.3095 · 2.40 Impact Factor
Show more