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PMID:12119102

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Citation

Butchbach, ME, Lai, L and Lin, CL (2002) Molecular cloning, gene structure, expression profile and functional characterization of the mouse glutamate transporter (EAAT3) interacting protein GTRAP3-18. Gene 292:81-90

Abstract

Glutamate is an important amino acid implicated in energy metabolism, protein biosynthesis and neurotransmission. The Na(+)-dependent high-affinity excitatory amino acid transporter EAAT3 (EAAC1) facilitates glutamate uptake into most cells. Recently, a novel rat EAAT3-interacting protein called GTRAP3-18 has been identified by a yeast two-hybrid screening. GTRAP3-18 functions as a negative modulator of EAAT3-mediated glutamate transport. In order to further understand the function and regulation of GTRAP3-18, we cloned the mouse orthologue to GTRAP3-18 and determined its gene structure and its expression pattern. GTRAP3-18 encodes a 188-residue hydrophobic protein whose sequence is highly conserved amongst vertebrates. Mouse and human GTRAP3-18 genes contain three exons separated by two introns. The GTRAP3-18 gene is found on mouse chromosome 6D3 and on human chromosome 3p14, a susceptibility locus for cancer and epilepsy. GTRAP3-18 protein and RNA were found both in neuronal rich regions of the brain and in non-neuronal tissues such as the kidney, heart and skeletal muscle. Mouse GTRAP3-18 inhibited EAAT3-mediated glutamate transport in a dose-dependent manner. These studies show that GTRAP3-18 is a ubiquitously expressed protein that functions as a negative regulator of EAAT3 function.

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Keywords

Amino Acid Sequence; Amino Acid Transport System X-AG; Animals; Base Sequence; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Cloning, Molecular; DNA, Complementary/chemistry; DNA, Complementary/genetics; Excitatory Amino Acid Transporter 3; Gene Expression Profiling; Genes/genetics; Glutamate Plasma Membrane Transport Proteins; Glutamic Acid/drug effects; Glutamic Acid/pharmacokinetics; Immunoblotting; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; RNA/genetics; RNA/metabolism; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Symporters

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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