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G-protein coupled receptor ligand 15 GPR15 is an orphan G protein-coupled receptor (GPCR) that is found in lymphocytes. It functions as a co-receptor of simian immunodeficiency virus and HIV-2 and plays a role in the trafficking of T cells to the lamina propria in the colon and to the skin. An activating ligand named GPR15L is shown to bind GPR15 and attract GPR15-expressing T cells including lymphocytes in colon-draining lymph nodes and thymic precursors of dermal epithelial T cell. This 9kDa CC-motif containing cationic polypeptide has been previously described as the 57 amino acid antimicrobial peptide AP-57, and as a Sushi Containing Domain-2 (SUSD2)-binding factor (CSBF), capable of inhibiting the growth of intestinal epithelial cancer cell lines. The chemokine is expressed by epithelial cells in gastrointestinal and genitourinary mucosae and in the skin. In humans GPR15L, is encoded by the gene C10ORF99 and has some features similar to the CC family of chemokines. However, it lacks significant homology to classic CC and CXC chemokines, yet shares many features with them, including a cationic domain predicted to comprise two disulfide bonds and a highly conserved GPCR-activating terminal peptide. Furthermore, the activating peptides of CC chemokines are typically located at the N-terminus, while that of GPR15L is C-terminal, a feature that it shares with some other GPCR ligands like chemerin and apela. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",