SLC1A5 (Solute Carrier Family 1 Member 5), also known as ASCT2 (Alanine-Serine-Cysteine Transporter 2), is a sodium-dependent neutral amino acid transporter critical for cellular uptake of glutamine, alanine, serine, and cysteine[@amino2017]. ASCT2 is the primary glutamine transporter in the blood-brain barrier and plays essential roles in nitrogen metabolism, glutathione synthesis, and cellular signaling through the mTOR pathway. It is highly expressed in many cancers where it supports rapid glutamine metabolism[@slc2020].
The SLC1A5 gene is located on chromosome 19q13.33 and encodes a 541-amino acid protein with 10 transmembrane domains. Transport is driven by the Na+ gradient and couples the uptake of neutral amino acids to Na+ ion cotransport. ASCT2 is upregulated in many cancers and represents a therapeutic target for cancer treatment.
SLC1 family transporters are evolutionarily conserved:
| Species | SLC1A5/ASCT2 | Identity |
|---|---|---|
| D. rerio | slc1a5 | 73% |
| G. gallus | SLC1A5 | 81% |
| M. musculus | Slc1a5 | 86% |
| R. norvegicus | Slc1a5 | 88% |
| H. sapiens | SLC1A5 | 100% |
| Tissue | Expression | Pathological Relevance |
|---|---|---|
| Blood-brain barrier | Very High | Brain glutamine supply |
| Intestine | High | Nutrient absorption |
| Lung | High | Surfactant metabolism |
| Breast | High | Cancer upregulation |
| Brain | Moderate | Neuronal function |
| Immune cells | High | Immune activation |
| Property | Value |
|---|---|
| Gene Symbol | SLC1A5 |
| Full Name | Solute Carrier Family 1 Member 5 |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 6510 |
| Ensembl ID | ENSG00000105374 |
| UniProt ID | P52802 |
| OMIM | 109440 |
| Gene Type | Protein coding |
| Property | Value |
|---|---|
| Protein Name | ASCT2 (neutral amino acid transporter) |
| Molecular Weight | 56 kDa |
| Amino Acids | 541 |
| Subcellular Localization | Plasma membrane |
| Transporter Family | SLC1 (high-affinity glutamate) |
ASCT2 catalyzes Na+-dependent neutral amino acid exchange[@heteromeric2005]:
| Substrate | Affinity (Km) | Physiological Role |
|---|---|---|
| Glutamine | 0.2-0.5 mM | Primary substrate |
| Alanine | 0.3-0.8 mM | Energy source |
| Serine | 0.4-1.0 mM | Biosynthesis |
| Cysteine | 0.5-1.2 mM | Glutathione precursor |
| Glutamate* | Low | Counter-exchange |
*Note: ASCT2 has very low affinity for glutamate; SLC1A2/A3 are glutamate-specific.
ASCT2 is critical for[@bronger2019]:
ASCT2 is a major glutamine transporter in cancer[@fuchs2018]:
ASCT2 dysfunction may contribute to[@nathaniel2019]:
ASCT2 is the primary glutamine transporter at the BBB[@broer2014]:
| Variant | Effect | Association |
|---|---|---|
| Amplification | Overexpression | Multiple cancers |
| c.1004C>T | Missense | Breast cancer |
| rs1124171 | Promoter | Lung cancer |
| Agent | Mechanism | Stage |
|---|---|---|
| V-9302 | ASCT2 inhibitor | Preclinical |
| GPNA | Substrate analog | Research |
| Erastin | Ferroptosis inducer | Research |
| Domain | Residues | Function |
|---|---|---|
| N-terminus | 1-50 | Targeting signal |
| TM1-5 | 51-280 | Transport core |
| Hairpin loop | 281-320 | Substrate binding |
| TM6-10 | 321-500 | Transport core |
| C-terminus | 501-541 | Regulatory |
| Protein | Interaction | Function |
|---|---|---|
| SLC7A5 | Heterodimer | Amino acid exchange |
| mTORC1 | Signaling | Growth regulation |
| GLS | Metabolic | Glutamine metabolism |
| System L | Counter-transport | Efflux pathway |
| Biomarker | Cancer Type | Change |
|---|---|---|
| ASCT2 expression | Lung cancer | Increased 3-5x |
| ASCT2 expression | Breast cancer | Increased 2-4x |
| ASCT2 expression | Colorectal | Increased 2-3x |
ASCT2 is important for[@aldrich2020]: