Identification of a novel cytosolic tocopherol-binding protein: structure, specificity, and tissue distribution.
Alpha-tocopherol plays an important role as a lipid-soluble antioxidant. It is present in all major mammalian cell types and shows tissue-specific distribution. This suggests the presence of specific proteins involved in intracellular distribution or metabolism of alpha-tocopherol. A diminution of tocopherol plasma concentrations contributes to the development of diseases such as vitamin E deficiency (AVED), atherosclerosis, and prostate cancer. Further evidence has been obtained for the existence of sites in cellular metabolism and signal transduction where alpha-tocopherol potentially plays a regulatory role. A signal transduction modulation specific for alpha-tocopherol has been described in several model systems. Using radioactively labeled alpha-tocopherol as tracer, we have isolated a new alpha-tocopherol-associated protein (TAP) from bovine liver. This protein has a molecular mass of 46 kDa and an isoelectric point of 8.1. From its partial amino acid sequence, a human gene has been identified with high homology to the newly described protein. Sequence analysis has established that the new TAP has structural motifs suggesting its belonging to a family of hydrophobic ligand-binding proteins (RALBP, CRALBP, alpha-TTP, SEC 14, PTN 9, RSEC 45). Human TAP has been cloned into Escherichia coli, and its tissue-specific expression has been assessed by Northern blot analysis.
Stocker
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Institute of Biochemistry and Molecular Biology, University of Bern, Switzerland.
Zimmer
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Spycher
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Azzi
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D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003488:Cyanogen Bromide; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D011467:Prostate / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013379:Substrate Specificity; D014316:Tritium; D014810:Vitamin E / Q000378:metabolism
D002352:Carrier Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C017763:alpha-tocopherol transfer protein; D014316:Tritium; D014810:Vitamin E; D003488:Cyanogen Bromide