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J Biol Chem, Vol. 273, Issue 49, 32437-32445, December 4, 1998
From the Departament de Bioquímica i Biologia Molecular and
the We have identified a new human
cDNA (y+L amino acid transporter-1
(y+LAT-1)) that induces system y+L transport
activity with 4F2hc (the surface antigen 4F2 heavy chain) in oocytes.
Human y+LAT-1 is a new member of a family of polytopic
transmembrane proteins that are homologous to the yeast high affinity
methionine permease MUP1. Other members of this family, the
Xenopus laevis IU12 and the human KIAA0245 cDNAs, also
co-express amino acid transport activity with 4F2hc in oocytes, with
characteristics that are compatible with those of systems L and
y+L, respectively. y+LAT-1 protein forms a
Identification and Characterization of a Membrane Protein
(y+L Amino Acid Transporter-1) That Associates with
4F2hc to Encode the Amino Acid Transport Activity
y+L
A CANDIDATE GENE FOR LYSINURIC PROTEIN INTOLERANCE
, Departament de Fisiologia (Immunologia), Facultat de
Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028 Barcelona, Spain and the ** Laboratory of Molecular Embryology
NICHD, National Institutes of Health, Bethesda,
Maryland 20892-5431
135-kDa, disulfide bond-dependent heterodimer with 4F2hc
in oocytes, which upon reduction results in two protein bands of 85
kDa (i.e. 4F2hc) and 40 kDa (y+LAT-1).
Mutation of the human 4F2hc residue cysteine 109 (Cys-109) to serine
abolishes the formation of this heterodimer and drastically reduces the
co-expressed transport activity. These data suggest that
y+LAT-1 and other members of this family are different 4F2
light chain subunits, which associated with 4F2hc, constitute different amino acid transporters. Human y+LAT-1 mRNA is
expressed in kidney peripheral blood leukocytes lung > placenta = spleen > small intestine. The human
y+LAT-1 gene localizes at chromosome 14q11.2
(17cR 374 kb from D14S1350), within the lysinuric protein
intolerance (LPI) locus (Lauteala, T., Sistonen, P., Savontaus, M. L., Mykkanen, J., Simell, J., Lukkarinen, M., Simmell, O., and Aula, P. (1997) Am. J. Hum. Genet. 60, 1479-1486). LPI is an
inherited autosomal disease characterized by a defective dibasic amino
acid transport in kidney, intestine, and other tissues. The pattern of
expression of human y+LAT-1, its co-expressed transport
activity with 4F2hc, and its chromosomal location within the LPI locus,
suggest y+LAT-1 as a candidate gene for LPI.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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A. Chairoungdua, Y. Kanai, H. Matsuo, J. Inatomi, D. K. Kim, and H. Endou Identification and Characterization of a Novel Member of the Heterodimeric Amino Acid Transporter Family Presumed to be Associated with an Unknown Heavy Chain J. Biol. Chem., December 21, 2001; 276(52): 49390 - 49399. [Abstract] [Full Text] [PDF]
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