Structural and phylogenetic characterization of human SLURP-1, the first secreted mammalian member of the Ly-6/uPAR protein superfamily

Members of the Ly-6/uPAR protein family share one or several repeat units o f the Ly-6/uPAR domain that is defined by a distinct disulfide bonding patt ern between 8 or 10 cysteine residues. The Ly-6/uPAR protein family can be divided into two subfamilies. One comprises GPI-anchored glycoprotein recep tors with 10 cysteine residues. The other subfamily includes the secreted s ingle-domain snake and frog cytotoxins, and differs significantly in that i ts members generally possess only eight cysteines and no GPI-anchoring sign al sequence. We report the purification and structural characterization of human SLURP-1 (secreted mammalian Ly-6/uPAR related protein 1) from blood a nd urine peptide libraries. SLURP-1 is encoded by the ARS (component B)-81/ s locus, and appears to be the first mammalian member of the Ly-6/uPAR fami ly lacking a GPI-anchoring signal sequence. A phylogenetic analysis based o n the SLURP-1 primary protein structure revealed a closer relationship to t he subfamily of cytotoxins. Since the SLURP-1 gene maps to the same chromos omal region as several members of the Ly-6/uPAR subfamily of glycoprotein r eceptors, it is suggested that both biologically distinct subfamilies might have co-evolved from local chromosomal duplication events.