| 2005 |
SLC6A15 (SBAT1) functions as a sodium-coupled transporter of hydrophobic, zwitterionic alpha-amino and imino acids when expressed in Xenopus oocytes, with strong preference for branched-chain amino acids (leucine, isoleucine, valine) and methionine (K0.5 80-160 µM); it excludes aromatic or charged amino acids, beta-amino acids, glycine, and GABA. Transport is highly temperature-dependent (Q10=9) and inhibited at acidic pH. PKC activation reduces the plasma-membrane population of SBAT1 protein. |
Xenopus oocyte heterologous expression, radiolabeled substrate uptake assays, pharmacological manipulation (PKC activation) |
Biochemical and biophysical research communications |
High |
16226721
|
| 2007 |
In cortical synaptosomes from v7-3 (SLC6A15) knockout mice, sodium-dependent proline uptake was reduced by 15% and leucine uptake by 40% compared to wild-type controls, establishing SLC6A15 as a contributor to synaptosomal proline and leucine transport in vivo. |
SLC6A15 knockout mouse model; radiolabeled amino acid uptake into cortical synaptosomes |
Brain research |
High |
17931606
|
| 2000 |
Human v7-3 (SLC6A15) encodes a 730 amino acid protein with 12 predicted transmembrane domains, intracellular N- and C-termini, and large extracellular loops between TM3-4 and TM7-8 with N-linked glycosylation sites; transfection experiments showed v7-3 is expressed at the cell surface (plasma membrane localization), in contrast to the related NTT5 which is predominantly intracellular. |
Epitope-tagged transporter construct transfection, subcellular localization by cellular imaging/fractionation; bioinformatic topology prediction |
Genomics |
Medium |
11112352
|
| 2013 |
SLC6A15 knockout mice show lower reduction in food intake and lower neuronal activation in the ventromedial hypothalamic nucleus (VMH) in response to intracerebroventricular leucine injections compared to wild-type mice, establishing SLC6A15 as mediating the anorexigenic effect of leucine in the brain. B0AT2 (SLC6A15) immunoreactivity was found in neurons (including GABAergic neurons and spinal cord motor neurons) and in astrocytes near ventricles, and co-localized with cytokeratin and diazepam binding inhibitor (DBI) in choroid plexus epithelial cells. |
Slc6a15 knockout mice, food intake assay with leucine injection, c-Fos neuronal activation immunohistochemistry, immunohistochemistry and in situ hybridization for tissue distribution |
PloS one |
High |
23505546
|
| 2013 |
SLC6A15 knockout attenuates leucine's ability to reduce normal chow intake and weight gain on high-fat diet in a sex-selective fashion in mice, supporting a role for brain SLC6A15 in leucine-mediated control of food intake and obesity-related phenotypes. |
Slc6a15 knockout mice, dietary feeding assays with leucine supplementation, body weight measurement |
PloS one |
Medium |
24023709
|
| 2015 |
Loss of SLC6A15 in knockout mice reduces hippocampal tissue levels of proline and other neutral amino acids, decreases overall tissue glutamate and glutamine, while simultaneously increasing basal extracellular glutamate tone. Conversely, hippocampal SLC6A15 overexpression increases glutamate/glutamine tissue concentrations. These neurochemical changes were linked to altered sensorimotor gating behavior. |
Slc6a15 knockout mice; virus-mediated hippocampal overexpression; hippocampal amino acid measurement (HPLC/NMR); in vivo microdialysis for extracellular glutamate; prepulse inhibition behavioral test |
Journal of psychiatric research |
High |
26228428
|
| 2015 |
Slc6a15 knockout mice show reduced anxiety- and depressive-like behavior following chronic social stress compared to wild-type littermates, while hippocampal SLC6A15 overexpression increases anxiety-like behavior at baseline. GluR1 (AMPA receptor subunit) expression in the dentate gyrus, but not GluR2 or NR1, is regulated by slc6a15 expression levels, implicating glutamatergic signaling as a downstream mechanism. |
Slc6a15 KO and virus-mediated hippocampal overexpression mouse models; chronic social stress paradigm; anxiety/depression behavioral tests; immunoblot for GluR1, GluR2, NR1 in dentate gyrus |
Stress (Amsterdam, Netherlands) |
Medium |
26585320
|
| 2017 |
Cre-inducible viral reduction of Slc6a15 selectively in NAc D2-medium spiny neurons (using D2-Cre and A2A-Cre mice) causes enhanced susceptibility to subthreshold social defeat stress, while restoring Slc6a15 expression in D2-neurons after chronic social defeat stress prevents social avoidance. Slc6a15 protein was unaltered in ChAT interneurons after chronic social defeat stress, indicating the effect is D2-MSN-specific. |
Cre-inducible viral vectors in D2-Cre and A2A-Cre mice; chronic and subthreshold social defeat stress; social interaction behavioral testing; immunofluorescence for Slc6a15 protein in ChAT interneurons |
The Journal of neuroscience |
High |
28576941
|
| 2013 |
Two rare non-synonymous coding variants in SLC6A15 were associated with significantly increased maximal [3H]proline uptake compared to the wildtype sequence in a cellular uptake assay, demonstrating that specific amino acid changes can alter transporter activity. |
Cellular [3H]proline uptake assay with wildtype vs. mutant SLC6A15 constructs; pooled targeted re-sequencing and individual re-genotyping |
PloS one |
Medium |
23874702
|
| 2020 |
Loss of SLC6A15 in primary hippocampal neurons results in: reduced release probability at glutamatergic synapses, increased mitochondrial function, higher GSH/GSSG redox ratio, and improved neurite outgrowth. Proteomics of Slc6a15-KO hippocampal tissue revealed differentially regulated proteins in metabolic, mitochondrial, and structural functional domains. |
Primary hippocampal neurons from Slc6a15-KO mice; proteomics (mass spectrometry); electrophysiology (glutamatergic synapse release probability); Seahorse metabolic assay (mitochondrial function); GSH/GSSG redox assay; neurite outgrowth imaging |
The European journal of neuroscience |
Medium |
33007132
|
| 2021 |
Ectopic overexpression of SLC6A15 in papillary thyroid cancer (PTC) cells impaired their migratory and invasive abilities in vitro, and intercellular adhesion molecule-1 (ICAM-1) was identified as involved in mediating these effects. |
SLC6A15 overexpression in PTC cell lines; Transwell migration and invasion assays; ICAM-1 expression analysis |
Journal of cellular biochemistry |
Low |
33690923
|
| 2025 |
SLC6A15 knockdown in MNT1 cells and primary melanocytes reduced melanin synthesis, downregulated melanogenesis-related genes (MITF, TYR, DCT), decreased tyrosinase activity, and reduced intracellular phenylalanine levels. UVB exposure upregulated SLC6A15, and SLC6A15 silencing abrogated UVB-induced pigmentation, establishing SLC6A15-mediated phenylalanine transport as a mechanism regulating melanogenesis. |
SLC6A15 knockdown (siRNA/shRNA) in melanocyte cell lines and primary melanocytes; Fontana-Masson staining; tyrosinase activity assay; RT-qPCR for melanogenesis genes; intracellular amino acid measurement; UVB irradiation experiments |
Journal of photochemistry and photobiology. B, Biology |
Medium |
41352278
|
| 2025 |
Ectopic overexpression of SLC6A15 in CD8+ T-cells was sufficient to restore effector function (cytotoxic capacity and protein synthesis) in tumor-infiltrating lymphocytes, demonstrating that SLC6A15-mediated amino acid transport can relieve amino acid insufficiency-driven translational suppression in the tumor microenvironment. |
SLC6A15 overexpression in primary CD8+ T-cells; tumor infiltrating lymphocyte functional assays; protein synthesis measurement; cytotoxicity assays |
bioRxivpreprint |
Low |
|
| 2026 |
High-throughput screening of 200,000 compounds identified the first selective inhibitors of B0AT2/SLC6A15, with a 1,5-benzodiazepine series showing IC50 ~250 nM in [3H]proline uptake assays in SLC6A15-overexpressing HEK293 cells and primary neurons, no detectable inhibition of SERT, DAT, GAT1, or NTT4/SLC6A17 (>80 µM), and dose-dependent stimulation of neurite outgrowth in primary neurons. |
High-throughput [3H]proline cellular uptake assay in SLC6A15-overexpressing HEK293 cells; selectivity profiling against related SLC6 transporters; neurite outgrowth assay in primary hippocampal neurons |
bioRxivpreprint |
Medium |
|
| 2026 |
Phosphoproteomic curation identified three predominant phosphorylation sites on SLC6A15: pS701, pS699, and pS687, with predicted upstream kinases MAPK3 and CDK12. Binary interactors identified include tyrosine-protein kinase Lyn, epidermal growth factor receptor, and calnexin. |
Computational curation and bioinformatic analysis of 3825 global phosphoproteomic datasets; kinase prediction; binary interactor analysis |
Omics : a journal of integrative biology |
Low |
41649124
|