Metargidin, a membrane-anchored metalloprotease-disintegrin protein with an RGD integrin binding sequence.
Cellular disintegrins are a family of membrane-anchored proteins with structural homology to snake venom metalloproteases and disintegrins. We report here the cDNA cloning and initial biochemical characterization of the first cellular disintegrin protein with an RGD sequence in its disintegrin domain, which we propose to name metargidin (for metalloprotease-RGD-disintegrin protein). The domain organization of metargidin is identical with that of previously reported members of the cellular disintegrin family, comprising (i) a pro- and a metalloprotease domain including a zinc-binding consensus motif, (ii) a disintegrin domain containing the RGD motif, (iii) a cysteine-rich domain, (iv) an epidermal growth factor-like domain, (v) a hydrophobic transmembrane domain, and (vi) a cytoplasmic tail with proline-rich sequences that could act as potential SH3 ligands. Antibodies raised against the cytoplasmic tail of metargidin recognize a glycoprotein of 110 kDa in MDA-MB-468 mammary epithelial carcinoma cells, which can be cell surface-biotinylated, indicating its localization in the plasma membrane. A second protein of 56 kDa co-immunoprecipitates with metargidin, suggesting that it is part of a protein complex. These features are consistent with a model in which metargidin is an integrin ligand which, as a transmembrane protein, might function in cell-cell adhesion and/or signaling.
Krätzschmar
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Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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D051722:ADAM Proteins; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D018076:DNA, Complementary; D019483:Disintegrins; D005260:Female; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000302:isolation & purification; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000737:chemistry* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009842:Oligopeptides; D009928:Organ Specificity; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D018076:DNA, Complementary; D019483:Disintegrins; D008024:Ligands; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid; D051722:ADAM Proteins; C098660:ADAM15 protein, human; D008666:Metalloendopeptidases