Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by the triad of tyrosinase-positive oculocutaneous albinism, bleeding diathesis due to storage-pool deficiency of platelets, and a lysosomal ceroid storage disease. The disorder is particularly frequent in Puerto Rico and in an isolated village in the Swiss Alps. We have used a linkage disequilibrium mapping approach to localize the HPS gene in both of these groups to a 0.6 centiMorgan interval in chromosome segment 10q23.1-q23.3. These results indicate that the Puerto Rican and Swiss forms of HPS are either allelic or that they result from mutations in very closely linked genes in this region. This region of distal chromosome 10q is syntenic to the region of mouse chromosome 19 that includes 'pale ear' (ep) and 'ruby-eye' (ru), which must be considered as potential murine homologues to human HPS.
Hum Mol Genet 1995 Sep
PMID:Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to chromosome 10q23.1-q23.3. 854 58

In the medaka fish (Oryzias latipes) many mutants for body color have been isolated. A typical example is the recessive oculocutaneous albino mutant i, which has amelanotic skin and red-colored eyes with no tyrosinase activity. To cast light on the molecular basis of the albino mechanism, we performed Southern blot analysis of genomic DNA from the mutant with an authentic tyrosinase gene probe; the results demonstrate that an extra 1.9 kb fragment is present inside the first exon. The insertion is responsible for the oculocutaneous albinism. About 80 copies of this fragment are present in the genomes of albino-i and wild-type fish; these repeated sequences are here designated Tol1 elements and the particular element found in the tyrosinase gene of albino-i is denoted Tol1-tyr. The nucleotide sequence of Tol1-tyr shows that the fragment (i) carries terminal inverted repeats of 14 bp, and (ii) is flanked by duplicated 8 bp segments of the host chromosome. These are properties of DNA-mediated transposable elements. Comparison of the nucleotide sequence of Tol1-tyr with other sequences in DNA databases, with special attention to sequences of transposable elements known to date, did not reveal any similarity. Thus, Tol1 constitutes a hitherto unknown family of DNA transposable elements.
Mol Gen Genet 1995 Dec 10
PMID:Insertion of a novel transposable element in the tyrosinase gene is responsible for an albino mutation in the medaka fish, Oryzias latipes. 855 44

In the DNA binding domain of microphthalmia-associated transcription factor (MITF), four mutations are reported: mi, Mi wh, mi ew, and mi or. MITFs encoded by the mi, Mi wh, mi ew, and Mi or mutant alleles (mi-MITF, Mi wh-MITF, Mi ew-MITF, and Mi or-MITF, respectively) interfered with the DNA binding of wild-type MITF, TFE3, and another basic helix-loop-helix leucine zipper protein in vitro. Polyclonal antibody against MITF was produced and used for investigating the subcellular localization of mutant MITFs. Immunocytochemistry and immunoblotting revealed that more than 99% of wild-type MITF and Mi wh-MITF located in nuclei of transfected NIH 3T3 and 293T cells. In contrast, mi-MITF predominantly located in the cytoplasm of cells transfected with the corresponding plasmid. When the immunoglobulin G (IgG)-conjugated peptides representing a part of the DNA binding domain containing mi and Mi wh mutations were microinjected into the cytoplasm of NRK49F cells, wild-type peptide and Mi wh-type peptide-IgG conjugate localized in nuclei but mi-type peptide-IgG conjugate was detectable only in the cytoplasm. It was also demonstrated that the nuclear translocation potential of Mi or-MITF was normal but that Mi ew-MITF was impaired as well as mi-MITF. In cotransfection assay, a strong dominant negative effect of Mi wh-MITF against wild-type MITF-dependent transactivation system on tyrosinase promoter was observed, but mi-MITF had a small effect. However, by the conjugation of simian virus 40 large-T-antigen-derived nuclear localization signal to mi-MITF, the dominant negative effect was enhanced. Furthermore, we demonstrated that the interaction between wild-type MITF and mi-MITF occurred in the cytoplasm and that mi-MITF had an inhibitory effect on nuclear localization potential of wild-type MITF.
Mol Cell Biol 1996 Mar
PMID:The recessive phenotype displayed by a dominant negative microphthalmia-associated transcription factor mutant is a result of impaired nucleation potential. 862 64

Whole cell hybrids and microcell hybrids between mouse fibroblasts and pigmented Syrian hamster melanoma cells were analyzed for coordinate regulation of melanocyte-specific gene products. Extinction of pigmentation was observed in whole-cell hybrids and in a microcell hybrid containing a single mouse chromosome (mouse chromosome 1). Analysis of melanocyte-specific transcripts using reverse transcription, combined with the polymerase chain reaction (RT-PCR), demonstrated that tyrosinase, TRP-1, TRP-2, and microphthalmia transcripts were all absent in unpigmented whole-cell hybrids and in the monochromosomal unpigmented microcell hybrid. A pigmented subclone of this microcell hybrid, however, re-expressed the tyrosinase, TRP-1, TRP-2, and microphthalmia genes. These data suggest that all of these genes are coordinately extinguished by a single fibroblast locus. Since the only fibroblast chromosome detected in the unpigmented microcell hybrid was mouse chromosome 1, these results also suggest that the extinguisher locus affecting the expression of the tyrosinase, TRP-1, TRP-2, and microphthalmia genes in hybrid cells is located on that mouse chromosome (or on a fragment of another chromosome present in the unpigmented monochromosomal microcell hybrid but undetected in our analyses). In contrast to the results with the melanocyte-specific genes mentioned above, transcripts for the melanocortin 1 receptor gene (MC1R) were present in the monochromosomal unpigmented microcell hybrid (although absent in the whole-cell hybrids). This suggests that regulation of MC1R gene expression is distinct from regulation of the other melanocyte-specific genes.
Somat Cell Mol Genet 1996 Jan
PMID:Coordinate extinction of melanocyte-specific gene expression in hybrid cells. 864 93

Dipteran arylphorin receptors, insect hexamerins, cheliceratan and crustacean hemocyanins, and crustacean and insect tyrosinases display significant sequence similarities. We have undertaken a systematic comparison of primary and secondary structures of these proteins. On the basis of multiple sequence alignments the phylogeny of these proteins was investigated. Hexamerin subunits, hemocyanin subunits, and tyrosinases share extensive similarities throughout the entire amino acid sequence. Our studies suggest the origin of arthropod hemocyanins from ancient tyrosinase-like proteins. Insect hexamerins likely evolved from hemocyanins of ancient crustaceans, supporting the proposed sister-group position of these subphyla. Arylphorin receptors, responsible for incorporation of hexamerins into the larval fat body of diptera, are related to hexamerins, hemocyanins, and tyrosinase. The receptor sequences display extensive similarities to the first and third domains of hemocyanins and hexamerins. In the middle region only limited amino acid conservation was observed. Elements important for hexamer formation are deleted in the receptors. Phylogenetic analysis indicated that dipteran arylphorin receptors diverged from ancient hexamerins, probably early in insect evolution.
J Mol Evol 1996 Jun
PMID:Common origin of arthropod tyrosinase, arthropod hemocyanin, insect hexamerin, and dipteran arylphorin receptor. 866 23

NIN1 is an essential gene for growth of the yeast Saccharomyces cerevisiae and was recently found to encode a component of the regulatory subunit of the 26S proteasome. The nin1-1 mutant is temperature sensitive and its main defect is in G1/S progression and G2/M progression at non-permissive temperatures. One of the two multicopy suppressors of nin1-1, SUN2 (SUppressor of Nin1-1), was found to encode a protein of 523 amino acids whose sequence is similar to those of Drosophila melanogaster diphenol oxidase A2 and the mouse mast-cell Tum(-) transplantation antigen, P91A. The C-terminal half of Sun2p was found to be functional as Sun2p at 25 degrees C, 30 degrees C, and 34 degrees C but not at 37 degrees C. The open reading frame (ORF) of the Drosophila diphenol oxidase A2 gene (Dox-A2) was obtained from a lambda phage cDNA library using the polymerase chain reaction technique. The Dox-A2 ORF driven by the TDH3 promoter complemented the phenotype of a strain deleted for sun2. This Dox-A2-dependent strain was temperature sensitive and accumulated dumb-bell-shaped cells, with an undivided nucleus at the isthmus, after temperature upshift. This morphology is similar to that of nin1-1 cells kept at a restrictive temperature. These results suggest that SUN2 is a functional counterpart of Dox-A2 and that these genes play a pivotal role in the cell cycle in each organism.
Mol Gen Genet 1996 May 23
PMID:A multicopy suppressor of nin1-1 of the yeast Saccharomyces cerevisiae is a counterpart of the Drosophila melanogaster diphenol oxidase A2 gene, Dox-A2. 866 24

In vitro experiments are reported showing that NAD(P)H:(quinone acceptor) oxidoreductase (QR), purified from Glycine max seedlings, reduces Leu- and Met-enkephalin-tyrosinase oxidation products, in the presence of NADH or NADPH. QR was not capable to catalyze the reduction of N-acetyl-dopaquinone formed by the cation of mushroom tyrosinase on N-acetyl-L-tyrosine, while it was able to reduce dopachrome. The results support the hypothesis that QR can inhibit the formation of melanin-like compounds, as catalyzed by the action of tyrosinase on Leu-enkephalin and Met-enkephalin. It is proposed that, in the presence of NAD(P)H as the electron donor, the inhibition occurs by the specific conversion of the dopachrome-derivative into the reduced precursor, leucodopachrome-derivative.
Biochem Mol Biol Int 1995 Oct
PMID:Effect of NAD(P)H:quinone oxidoreductase on tyrosinase-mediated oxidation of opioid neuropeptides Leu-enkephalin and Met-enkephalin. 867 15

The generation of transgenic mice with mammalian genes cloned in yeast artificial chromosomes (YACs) has generated great interest in the field of gene transfer into livestock. Many of the problems associated with standard transgenesis-such as lack of crucial regulator elements and position effects related to the integration site, which lead to variation in expression levels irrespective of the dose of the transgene-have been practically overcome. The large size of YAC-derived gene constructs (in excess of 1 Mb) facilitates the presence and transfer of all elements required for the faithful regulation of a gene. With the experiments discussed in this report, we have addressed the possibility of applying the obvious advantages of YAC transgenesis to farm animals. We have generated transgenic rabbits carrying a 250 kb YAC covering the mouse tyrosinase gene by pronuclear microinjection, and thus rescued the albino phenotype of the transgenic individuals. To date, this is the first demonstration of a successful transfer of large genetic units into the germ line of farm animals. This development might improve the occurrence of transgene expression at physiological levels and specific sites in livestock. YAC transgenesis therefore will be applied in genetic engineering, for example, in the production of pharmacologically interesting proteins encoded by large gene units and generating transgenic donors for xenotransplantation.
Mol Reprod Dev 1996 May
PMID:YAC transgenesis in farm animals: rescue of albinism in rabbits. 872 92

Phenoloxidase (PO) activity in the albumen gland (AG) and egg masses (EM) of Biomphalaria glabrata was assessed using high-performance liquid chromatography combined with electrochemical detection and colorimetric techniques. Both AG and EM extracts catalyzed the hydroxylation of L-tyrosine (monophenol oxidase activity, MPO) and oxidation of L-dopa (diphenol oxidase activity, DPO). However, no PO activity was found in the ovotestis. Both MPO and DPO activities in AG and EM were significantly inhibited by 1-phenyl-2-thiourea and inactivated by boiling. Approximately 35% of MPO and 44% of DPO activities were detected in the soluble fraction of homogenized EM, in contrast to that of homogenized AG, which contained about 5% and 12%, respectively, of MPO and DPO activities. N-acetyl-dopamine, a diphenolic compound, enhanced the hydroxylation of tyrosine by the PO. The presence of both MPO and DPO activities also was confirmed by the accelerated accumulation of dopachrome during incubation of EM extracts with L-tyrosine in the absence of ascorbate. Temperature and pH optima for this enzyme were 30 degrees C and 7.5, respectively. The potential roles of PO in egg formation in B glabrata are discussed.
Comp Biochem Physiol B Biochem Mol Biol 1996 Aug
PMID:Phenoloxidase activity in the reproductive system and egg masses of the pulmonate gastropod, Biomphalaria glabrata. 884 May 12

Dopamine-induced DNA damage was studied in vitro in the presence of the enzyme tyrosinase. Dopamine auto-oxidizes to form dopamine quinone, a reactive molecule which spontaneously decomposes to form additional reactive species that can modify cellular macromolecules. The conversion of dopamine to reactive dopamine quinone is accelerated by the enzyme tyrosinase. The objective of this study was to evaluate whether dopamine autoxidation would lead to DNA-reactive intermediates and whether tyrosinase would increase the rate of this reaction. Incubation of DNA with [3H]dopamine resulted in the concentration-dependent covalent incorporation of the labeled catecholamine into precipitable nucleic acid (DNA adduct formation). The presence of tyrosinase increased the incorporation by as much as two orders of magnitude. Antioxidants markedly reduced this incorporation, suggesting that dopamine free-radicals were critical in DNA modification. DNA adducts formed by dopamine in the presence of tyrosinase were visualized using 32P-postlabeling and thin layer chromatography. The results suggest that DNA modification by dopamine is accelerated by tyrosinase which, in turn, could contribute to destruction of dopaminergic neurons in vivo.
Brain Res Mol Brain Res 1996 Nov
PMID:Tyrosinase enhances the covalent modification of DNA by dopamine. 891 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>