Introduction of SLC7A5
SLC7A5, also known as large neutral amino acids transporter small subunit 1 (hLAT1), CD98LC or MPE16, is a protein that acts as an amino acid exchanger by transporting large neutral amino acids such as leucine, phenylalanine and tryptophan by exchange with intracellular glutamine. SLC7A5 belongs to the hetero(di)meric amino acid transporters (HATs) subgroup of SLC7 family of the larger APC (amino acid-polyamine-organo cation) superfamily. Encoded by the SLC7A5 gene, the architecture of SLC7A5 is characterized with 12 transmembrane domains (12TM), a cytoplasmic N and C termini with two conserved cysteine residues between TM3 and TM4. SLC7A5 gene is mapped to the chromosome 16q24.2 and contains 10 exons encoding a 55kD protein. SLC7A5 is widely expressed in many tissues, especially in brain endothelial cells, blood-brain barrier and inner blood retinal barrier with high levels.
|Basic Information of SLC7A5|
|Protein Name||Large neutral amino acids transporter small subunit 1|
|Aliases||hLAT1, CD98LC, MPE16|
|Organism||Homo sapiens (Human)|
Function of SLC7A5 Membrane Protein
It is documented that SLC7A5 content is abundant in various cancer cells. SLC7A5 has been demonstrated to play important roles in supplying amino acids to cancer cells and maintaining intra-cellular leucine, which is considered as a cardinal regulator in activation of mTORC1. Beyond the roles in proliferation, growth, and survival of cancer cells, SLC7A5 can mediate influx of amino acids in activated immune cells and the TCR-mediated induction of SLC7A5 is a critical metabolic checkpoint for T cells. Both pharmacological impairment or loss of function for SLC7A5 can dramatically restrain T cells proliferation, differentiation to effector cells, and cytokine production. The discovery of SLC7A5 in the placenta indicates a role for providing the essential amino acids needed for the growing foetus and the coincident transgenic animal model (SLC7A5-/- knockout mice) has been found to be embryonically lethal which may be due to its transport role at the placenta. Notably, SLC7A5 usually heterodimerizes with the glycoprotein CD98 (SLC3A2) through a conserved disulfide to form a complex mediating L-type (sodium independent exchange) of large neutral amino acids transport, which is responsible for uptake of essential amino acids in crucial body districts such as placenta and blood brain barrier.
Fig.1 System diagram of amino acid transporters (LAT1, ASCT2, and CD98) in modulation of T cell responses. (Wei, 2017)
Application of SLC7A5 Membrane Protein in Literature
The authors highlighted the structure, function, transport mechanism, and homology models of LAT1 to elucidate the potential substrate binding site, ligand-transporter interaction, and structure-function relationship. Moreover, the authors summarized different LAT1 inhibitors that have been identified so far to provide choices for cancer treatment.
This article used Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data to reveal that SLC7A5 mRNA and protein expression were strongly correlated with larger tumour size and higher grade in the highly proliferative breast cancer subtypes and in luminal B tumours, suggesting SLC7A5 may act as a potential therapeutic target.
The authors studied the gene and tissue localization of LAT1 and CD98 and identified basic requirements for substrates and substrate specificity of LAT1. The regulation of LAT1 expression and LAT1 associated diseases were also discussed in this article.
The authors revealed that HIF2α can bind to the proximal promoter of Slc7a5 to upregulate expression of the amino acid carrier SLC7A5, subsequently increase the activity of mTORC1 pathway.
The review summarized the interaction network of key nutrients (glucose, amino acids, and lipids), their sensors and transporters in response to T cell activation in infectious diseases. They also briefly discussed the regulation of T cell responses by oxygen and energy sensing mechanisms.
SLC7A5 Preparation Options
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