Human alpha-tocopherol transfer protein: cDNA cloning, expression and chromosomal localization.
alpha-Tocopherol transfer protein (alpha TTP), 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 alpha TTP in human liver by isolating its cDNA from a human liver cDNA library. The cDNA for human alpha TTP predicts 278 amino acids with a calculated molecular mass of 31,749, and the sequence exhibits 94% similarity with rat alpha TTP at the amino acid level. The recombinant human alpha TTP expressed in Escherichia coli exhibits both alpha-tocopherol transfer activity in an in vitro assay and cross-reactivity to the anti-(rat alpha TTP) monoclonal antibody. Northern blot analysis revealed that human alpha TTP is expressed in the liver like rat alpha TTP. The human and rat alpha TTPs 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 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 deficiency (AVED). The relationship between alpha TTP and AVED will be discussed.
Arita
M
M
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Sato
Y
Y
Miyata
A
A
Tanabe
T
T
Takahashi
E
E
Kayden
H J
HJ
Arai
H
H
Inoue
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009928:Organ Specificity; D011994:Recombinant Proteins; D017385:Sequence Homology
D002352:Carrier Proteins; D018076:DNA, Complementary; D011994:Recombinant Proteins; C017763:alpha-tocopherol transfer protein