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.
Adermann
K
K
Lower Saxony Institute for Peptide Research (IPF), Hannover, Germany.
Wattler
F
F
Wattler
S
S
Heine
G
G
Meyer
M
M
Forssmann
W G
WG
Nehls
M
M
D000818:Animals; D000950:Antigens, Ly / Q000097:blood / Q000737:chemistry* / Q000652:urine; D001001:Anura; D003603:Cytotoxins / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry; D019151:Peptide Library; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012911:Snakes; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood / Q000737:chemistry* / Q000652:urine
D000950:Antigens, Ly; D003603:Cytotoxins; D019151:Peptide Library; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator