Human α-tocopherol transfer protein: cDNA cloning, expression and chromosomal localization

α-Tocopherol transfer protein (αTTP), which specifically binds this vitamin and enhances its transfer between separate membranes, was previously isolated from rat liver cytosol. In the current study we demonstrated the presence of αTTP in human liver by isolating its cDNA from a human liver cDNA library. The cDNA for human αTTP predicts 278 amino acids with a calculated molecular mass of 31749, and the sequence exhibits 94% similarity with rat αTTP at the amino acid level. The recombinant human αTTP expressed in Escherichia coli exhibits both α-tocopherol transfer activity in an in vitro assay and crossreactivity to the anti-(rat αTTP) monoclonal antibody. Northern blot analysis revealed that human αTTP is expressed in the liver like rat αTTP. The human and rat αTTPs show structural similarity with other apparently unrelated lipid-binding/transfer proteins, i.e, retinaldehyde-binding protein present in retina, and yeast SEC14 protein, which possesses phosphatidylinositol/phosphatidylcholine transfer activity. Both Southern-blot hybridization of human-hamster somatic cell hybrid lines and fluorescence in situ hybridization revealed a single αTTP gene corresponding to the 8q13.1-13.3 region of chromosome 8, which is identical to the locus of a recently described clinical disorder, ataxia with selective vitamin E deficiency (AVED). The relationship between αTTP and AVED will be discussed.