SLC38A9
Domain
The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex (PubMed:25561175, PubMed:25567906). The cytosolic N-terminus part of the protein destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC (PubMed:32868926). The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and upon arginine binding, leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer (PubMed:25561175, PubMed:25567906, PubMed:30181260). The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state) (By similarity).
The CARC and CRAC motifs mediate binding to cholesterol.
Function
Lysosomal amino acid transporter involved in the activation of mTORC1 in response to amino acid levels (PubMed:25561175, PubMed:25567906, PubMed:29053970). Probably acts as an amino acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:25567906, PubMed:29053970). Following activation by amino acids, the Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:25561175, PubMed:25567906). SLC38A9 mediates transport of amino acids with low capacity and specificity with a slight preference for polar amino acids (PubMed:25561175, PubMed:25567906). Acts as an arginine sensor (PubMed:25567906, PubMed:29053970, PubMed:31295473). Following activation by arginine binding, mediates transport of L-glutamine, leucine and tyrosine with high efficiency, and is required for the efficient utilization of these amino acids after lysosomal protein degradation (PubMed:29053970, PubMed:31295473). However, the transport mechanism is not well defined and the role of sodium is not clear (PubMed:25561175, PubMed:31295473). Can disassemble the lysosomal folliculin complex (LFC), and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC (PubMed:32868926). Acts as an cholesterol sensor that conveys increases in lysosomal cholesterol, leading to lysosomal recruitment and activation of mTORC1 via the Rag GTPases (PubMed:28336668). Guanine exchange factor (GEF) that, upon arginine binding, stimulates GDP release from RRAGA and therefore activates the Rag GTPase heterodimer and the mTORC1 pathway in response to nutrient sufficiency (PubMed:30181260).
Post-translational modifications
Glycosylated.
Sequence Similarities
Belongs to the amino acid/polyamine transporter 2 family. SLC38A9 subfamily.
Cellular localization
- Lysosome membrane
- Multi-pass membrane protein
- Late endosome membrane
- Multi-pass membrane protein
Alternative names
URLC11, SLC38A9, Neutral amino acid transporter 9, Solute carrier family 38 member 9, Up-regulated in lung cancer 11