Target intelligence / Profile preview

Alanine-serine-cysteine transporter (ASCT)

Target
ASCT
Molecular classification
Transporter, Solute carrier family (SLC1 family), Amino acid transporter
01

Overview

The alanine-serine-cysteine transporters (ASCT) generally refer to a family of neutral amino acid transporters, most notably ASCT1 (SLC1A4) and ASCT2 (SLC1A5) in humans. These are well-characterized membrane transport proteins involved in amino acid exchange, with important roles in physiology and disease. They belong to the SLC1 family and are localized to the plasma membrane of various tissues. They catalyze the Na⁺-dependent or Na⁺-independent exchange of small neutral amino acids like alanine, serine, and, in some contexts, cysteine and threonine. ASCT2's main physiological role is glutamine transport, which is crucial for cell proliferation, particularly in cancer, while ASCT1 is more dominant in the central nervous system for serine and glycine regulation. Both are considered therapeutic targets, with ASCT2 being actively pursued for anticancer strategies. Although the term 'Alanine-serine-cysteine transporter' is generic and accurate, the actual substrate specificity for 'cysteine' is debatable, with substrate selectivity leaning towards alanine, serine, threonine, and glutamine. Another related transporter, Asc-1 (SLC7A10), is sometimes referred to as 'alanine-serine-cysteine-1' and is prominent in CNS glycine/D-serine regulation. Dysfunction or blockade of these transporters can lead to significant neurological and metabolic consequences.

Other names
Alanine-serine-cysteine transporter 1SLC1A4ASCT1Alanine-serine-cysteine transporter 2SLC1A5ASCT2
02

Mechanism of action

Competitive inhibition of amino acid transport: Many drugs or research tools act by blocking substrate binding or exchange. Disruption of glutamine uptake impairs cancer cell growth by metabolic starvation.

03

Biological functions

Regulation of amino acid homeostasisSynaptic transmission (particularly glycine, serine)Modulation of neurotransmitter pools in CNS (notably Asc-1/SLC7A10 for D-serine/glycine)Supply of glutamine and other neutral amino acids to metabolically active cellsCell proliferation (especially in cancers via glutamine uptake)
04

Disease associations

Cancer (ASCT2 upregulated in many cancers, supporting rapid growth)Neurological disease (deficiency or dysfunction associated with neurodevelopmental phenotypes and seizures; Asc-1/SLC7A10 associated with hyperekplexia)Inflammation (upregulated in inflammatory states for amino acid supply)Metabolic disordersImmune modulation
05

Safety considerations

Potential CNS toxicity (impairment of neurotransmission, risk of seizures or neurodevelopmental issues)Amino acid homeostasis disturbanceSelectivity (discrimination between different SLC1 family members to minimize off-target effects and toxicity)
06

Interacting drugs

Drugs that target ASCT2 (SLC1A5) as glutamine antagonists

5 more in the full profile.

07

Biomarkers

ASCT2 (SLC1A5) expression (for tumors with high glutamine demand)No validated fluid or imaging biomarker based on transporter function in clinical use

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