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

Published online by Cambridge University Press:  01 April 1999

KNUT ADERMANN ,
FRANK WATTLER ,
SIGRID WATTLER ,
GABRIELE HEINE ,
MARKUS MEYER ,
WOLF-GEORG FORSSMANN  and
MICHAEL NEHLS
KNUT ADERMANN
Affiliation:
Lower Saxony Institute for Peptide Research (IPF), Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany
FRANK WATTLER
Affiliation:
Lexicon Genetics Inc., 4000 Research Forest Drive, The Woodlands, Texas 77381
SIGRID WATTLER
Affiliation:
Lower Saxony Institute for Peptide Research (IPF), Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany Lexicon Genetics Inc., 4000 Research Forest Drive, The Woodlands, Texas 77381
GABRIELE HEINE
Affiliation:
Lower Saxony Institute for Peptide Research (IPF), Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany
MARKUS MEYER
Affiliation:
Lower Saxony Institute for Peptide Research (IPF), Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany
WOLF-GEORG FORSSMANN
Affiliation:
Lower Saxony Institute for Peptide Research (IPF), Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany
MICHAEL NEHLS
Affiliation:
Lower Saxony Institute for Peptide Research (IPF), Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany Lexicon Genetics Inc., 4000 Research Forest Drive, The Woodlands, Texas 77381
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Abstract

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.

Keywords

CD59disulfide bondsfrog toxingene locusLy-6 antigensecretionsnake toxinurokinase-type plasminogen activator receptor (uPAR)
Type
Research Article
Information
Protein Science , Volume 8 , Issue 4 , April 1999 , pp. 810 - 819
Copyright
© 1999 The Protein Society

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