HUMAN ALPHA-TOCOPHEROL TRANSFER PROTEIN - CDNA CLONING, EXPRESSION AND CHROMOSOMAL LOCALIZATION

alpha-Tocopherol transfer protein (alpha TTP), which specifically bind s this vitamin and enhances its transfer between separate membranes, w as previously isolated from rat liver cytosol. In the current study we demonstrated the presence of alpha TTP in human liver by isolating it s cDNA from a human liver cDNA library. The cDNA for human alpha TTP p redicts 278 amino acids with a calculated molecular mass of 31749, and the sequence exhibits 94% similarity with rat alpha TTP at the amino acid level. The recombinant human alpha TTP expressed in Escherichia c oli exhibits both alpha-tocopherol transfer activity in an in vitro as say and cross-reactivity to the anti-(rat alpha TTP) monoclonal antibo dy. Northern blot analysis revealed that human alpha TTP is expressed in the liver like rat alpha TTP. The human and rat alpha TTPs show str uctural similarity with other apparently unrelated lipid-binding/trans fer proteins, i.e. retinaldehyde-binding protein present in retina, an d yeast SEC14 protein, which possesses phosphatidylinositol/phosphatid ylcholine transfer activity. Both Southern-blot hybridization of human -hamster somatic cell hybrid lines and fluorescence in situ hybridizat ion revealed a single alpha TTP 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 deficienc y (AVED). The relationship between alpha TTP acid AVED will be discuss ed.