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 of the Ly‐6/uPAR domain that is defined by a distinct disulfide bonding pattern between 8 or 10 cysteine residues. The Ly‐6/uPAR protein family can be divided into two subfamilies. One comprises GPI‐anchored glycoprotein receptors with 10 cysteine residues. The other subfamily includes the secreted single‐domain snake and frog cytotoxins, and differs significantly in that its members generally possess only eight cysteines and no GPI‐anchoring signal sequence. We report the purification and structural characterization of human SLURP‐1 (secreted mammalian Ly‐6/uPAR related protein 1) from blood and 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 family lacking a GPI‐anchoring signal sequence. A phylogenetic analysis based on the SLURP‐1 primary protein structure revealed a closer relationship to the subfamily of cytotoxins. Since the SLURP‐1 gene maps to the same chromosomal region as several members of the Ly‐6/uPAR subfamily of glycoprotein receptors, it is suggested that both biologically distinct subfamilies might have co‐evolved from local chromosomal duplication events.

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