biostudies-literatureYu JNational Natural Science Foundation of ChinaBCJ20253418https://www.ebi.ac.uk/biostudies/studies/S-EPMC12905490biostudies-literatureUnknown483(2)C-X-C motif chemokine ligand 17 (CXCL17) and its receptor G protein-coupled receptor 25 (GPR25) have been identified as a significant pair in regulating immunity, but CXCL17 orthologs have not yet been identified from non-mammalian vertebrates. This study aimed to identify and characterize non-mammalian CXCL17 orthologs based on key features of mammalian CXCL17s, such as a C-terminal Xaa-Pro-Yaa motif, a signal peptide, and six cysteine residues. Two possible CXCL17 paralogs were identified from zebrafish (Danio rerio): Dr-CXCL17 (encoded by zgc:158701) and Dr-CXCL17-like (encoded by si:dkey-112a7.5). Both are previously uncharacterized proteins with unknown functions because they lack overall sequence similarity to known mammalian CXCL17s. For functional characterization, recombinant Dr-CThe Biochemical journalIdentification and functional characterization of two CXCL17 paralogs from zebrafish.PMC1290549031971193Guo ZYLiu YLYu JWang JJXu ZGHu WFfalseIdentification and functional characterization of two CXCL17 paralogs from zebrafish.C-X-C motif chemokine ligand 17 (CXCL17) and its receptor G protein-coupled receptor 25 (GPR25) have been identified as a significant pair in regulating immunity, but CXCL17 orthologs have not yet been identified from non-mammalian vertebrates. This study aimed to identify and characterize non-mammalian CXCL17 orthologs based on key features of mammalian CXCL17s, such as a C-terminal Xaa-Pro-Yaa motif, a signal peptide, and six cysteine residues. Two possible CXCL17 paralogs were identified from zebrafish (Danio rerio): Dr-CXCL17 (encoded by zgc:158701) and Dr-CXCL17-like (encoded by si:dkey-112a7.5). Both are previously uncharacterized proteins with unknown functions because they lack overall sequence similarity to known mammalian CXCL17s. For functional characterization, recombinant Dr-C2026-01-01T00:00:00Z2026 Jan2026-07-15T21:27:38.716Z2026-07-09T10:14:19.148ZS-EPMC129054904152165510.1042/BCJ20253418