2.A.1.14.10
Lysosomal sialate transporter (Salla disease and infantile sialate storage disease protein, Sialin, of 419 aas and 12 TMSs (Morin et al., 2004)). Also transports glucuronic acid and aspartate. Structure-function studies have identify crucial residues and substrate-induced conformational changes (Courville et al., 2010). Also called SLC17A5. The substrate binding pocket has been identified based on modeling studies (Pietrancosta et al., 2012).  NAAG (N-acetylaspartylglutamate) an abundant neuropeptide in the vertebrate nervous system that is released from synaptic terminals in a calcium-dependent manner and acts as an agonist at the type II metabotropic glutamate receptor mGluR3, is transported into synaptic vesicles before it is secreted. Lodder-Gadaczek et al. 2013 demonstrate that vesicular uptake of NAAG and the related peptide NAAG2 (N-acetylaspartylglutamylglutamate) is mediated by sialin (SLC17A5). Sialin is probably the only vesicular transporter for NAAG and NAAG2, because transport of both peptides was not detectable in vesicles isolated from sialin-deficient mice.  Sialin also transports nitrate in the plasma membrane of salivary glands (Qin et al. 2012). Sialin interacts with nitrate and participates in the regulation of NO production and cell biological functions for body homeostasis (Wang and Qin 2022). Sialin mediates the flux of sialic acid from lysosomes to the cytoplasm (Li et al. 2022). Altered sialin mRNA expression in the main tissues of male type 2 diabetes rats has been documented (Yousefzadeh et al. 2023).  Base editing corrects the common Salla disease SLC17A5 c.115C>T variant (Harb et al. 2023).