Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structures of the human tyrosinase-related protein genes TYRP1 and TYRP2 have been determined and compared with that of the tyrosinase gene (TYR). The TYRP1 protein is encoded in 7 exons spread over 24 kb of genomic DNA. Characterization of a 55-kb contig encompassing the human TYRP2 locus reveals that the protein coding region is divided into 8 exons. All three members of the TYRP gene family share a common C-terminal membrane spanning exon. Examination of the position of other intron junctions suggests that TYRP1 was derived from a TYR duplication and then was itself duplicated to give rise to the TYRP2 gene. The evidence also suggests that at least some of the introns within the TYR, TYRP1, and TYRP2 coding regions were gained after duplication and that intron slippage is unlikely to have occurred.
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PMID:Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family. 853 77

The relative expression of a number of key mediators of human pigmentation including tyrosinase, tyrosinase related protein-1 (TYRP1), endothelin-1 and adrenocorticotrophic hormone (ACTH) proteins were analysed and quantified in immunohistochemically stained skin sections using semiquantitative computer assisted image analysis. Comparisons were made between a range of different ethnic skin types including European, Chinese, Mexican, Indian and African at both chronically photoexposed and photoprotected sites. Melanocyte number varied little with ethnicity except in the European group which had 60-80% more melanocytes than other skin types (P < 0.01, n = 10; Student Neuman-Keuls). However, melanocyte number was increased approximately twofold in chronically photoexposed skin of all ethnic groups (P < 0.001, n = 48; paired t-test). Tyrosinase protein expression in melanocytes did not vary with ethnicity, but TYRP1 protein was significantly elevated (approximately 2.6-fold) in darkly pigmented African and Indian skin types compared with lightly pigmented Mexican, Chinese and European skin types. In melanocytes from chronically photoexposed skin, there was a modest but significant increase in the expression of tyrosinase protein (approximately 1.2-fold, P < 0.001, n = 48; paired t-test), together with a significant and slightly larger increase in the expression of TYRP1 protein (approximately 1.6-fold, P < 0.005, n = 48; paired t-test). In contrast, the expression of endothelin-1 and ACTH showed no significant variation with either ethnicity or photoexposure. These data are consistent with the view that maintenance of a chronically hyperpigmented phenotype in chronically photoexposed human skin is largely the result of a stable increase in the number of tyrosinase positive melanocytes at these sites. Moreover, the observed ethnic variation in TYRP1 protein expression suggests that TYRP1 may play a significant role in mediating ethnic differences in melanogenesis and constitutive skin pigmentation in vivo.
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PMID:Ethnic variation in tyrosinase and TYRP1 expression in photoexposed and photoprotected human skin. 1251 23

Classical genetic studies in European rabbits (Oryctolagus cuniculus) suggested the presence of two alleles at the brown coat colour locus: a wild-type B allele that gives dense black pigment throughout the coat and a recessive b allele that in the homozygous condition (b/b genotype) produces brown rabbits that are unable to develop black pigmentation. In several other species, this locus is determined by mutations in the tyrosinase-related protein 1 (TYRP1) gene, encoding a melanocyte enzyme needed for the production of dark eumelanin. In this study, we investigated the rabbit TYRP1 gene as a strong candidate for the rabbit brown coat colour locus. A total of 3846 bp of the TYRP1 gene were sequenced in eight rabbits of different breeds and identified 23 single nucleotide polymorphisms (SNPs; 12 in intronic regions, five in exons and six in the 3'-untranslated region) and an insertion/deletion of 13 bp, in the 3'-untranslated region, organised in a few haplotypes. A mutation in exon 2 (g.41360196G>A) leads to a premature stop codon at position 190 of the deduced amino acid sequence (p.Trp190ter). Therefore, translation predicts a truncated TYRP1 protein lacking almost completely the tyrosinase domain. Genotyping 203 rabbits of 32 different breeds identified this mutation only in brown Havana rabbits. Its potential functional relevance in disrupting the TYRP1 protein and its presence only in brown animals strongly argue for this non-sense mutation being a causative mutation for the recessive b allele at the brown locus in Oryctolagus cuniculus.
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PMID:A premature stop codon in the TYRP1 gene is associated with brown coat colour in the European rabbit (Oryctolagus cuniculus). 2481 76