Figure 1.

EAAT5 is a member of the human glutamate transporter gene family. (A) The predicted amino acid sequences of human EAAT5 is shown in alignment with the other known human EAAT subtypes (1, 2). In this alignment, amino acid residues identical in four of the five sequences are shown in white on black lettering to illustrate the extensive amino acid sequence conservation in this gene family. Although the transmembrane topology of these transporters is not well defined, one possible model is indicated here. The poorly conserved amino- and carboxy-terminal sequences are likely to be intracellular, and eight regions with strong transmembrane (TM) scores are indicated by bars and suggested orientation (i, inside; o, outside). The large conserved hydrophobic sequence (LCHS) indicated between TMs VII and VIII may be membrane-associated. Possible N-linked glycosylation sites (N-X-S or T) in a large extracellular loop are boxed. (B) The carboxyl terminus of EAAT5 conforms to a sequence motif (E-S or T-X-V) involved in subcellular targeting. NMDA receptor subunits NR2A and NR2B (12) and potassium channel Kv1.4 (13) interact with PSD-95 via their C termini.