SLC15A4

Proton-coupled amino-acid transporter that mediates the transmembrane transport of L-histidine and some di- and tripeptides from inside the lysosome to the cytosol, and plays a key role in innate immune response. Preferably binds to short peptides with a basic residue at the first position and a hydrophobic residue at the second position. Able to transport a variety of di- and tripeptides, including carnosine and some peptidoglycans. Transporter activity is pH-dependent and maximized in the acidic lysosomal environment (By similarity). Involved in the detection of microbial pathogens by toll-like receptors (TLRs) and NOD-like receptors (NLRs), probably by mediating transport of bacterial peptidoglycans across the endolysosomal membrane: catalyzes the transport of certain bacterial peptidoglycans, such as muramyl dipeptide (MDP), the NOD2 ligand, and L-alanyl-gamma-D-glutamyl-meso-2,6-diaminoheptanedioate (tri-DAP), the NOD1 ligand. Required for TLR7, TLR8 and TLR9-mediated type I interferon (IFN-I) productions in plasmacytoid dendritic cells (pDCs). Independently of its transporter activity, also promotes the recruitment of innate immune adapter TASL to endolysosome downstream of TLR7, TLR8 and TLR9: TASL recruitment leads to the specific recruitment and activation of IRF5. Required for isotype class switch recombination to IgG2c isotype in response to TLR9 stimulation (By similarity). Required for mast cell secretory-granule homeostasis by limiting mast cell functions and inflammatory responses (By similarity)..

Function from UniProtKB (Q8N697), read 2026-09-23. CC BY 4.0.