Modularity of the slit protein. Characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactions.
Since our characterization of the slit cDNA sequence, encoding a protein secreted by glial cells and involved in the formation of axonal pathways in Drosophila, we have discovered that the protein contains two additional sequence motifs that are highly conserved in a variety of proteins. A search of the GenPept database with the 73 amino acids at the carboxy terminus of slit revealed that this region contains significant similarity to a carboxy-terminal domain found in six other exported proteins. This observation has allowed us to define a new carboxy-terminal protein motif. In addition, comparisons with a 202 amino acid domain residing between epidermal growth factor (EGF) repeats in slit shows this region to be conserved in laminin, agrin and perlecan and, strikingly, also to lie between EGF repeats in both agrin and perlecan. Our analysis suggests this motif is involved in mediating interactions among extracellular proteins. Consistent with our previous characterization of the slit protein, both new motifs are found only in extracellular proteins. The identification of these two conserved motifs in slit reveals that the entire 1469 amino acids of the protein are made up of modular regions similar to those conserved in other extracellular proteins.
Rothberg
J M
JM
Howard Hughes Medical Institute, Department of Cell Biology, Yale University, New Haven, CT 06511.
Artavanis-Tsakonas
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004330:Drosophila / Q000737:chemistry* / Q000378:metabolism; D029721:Drosophila Proteins; D006801:Humans; D007301:Insect Hormones / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D007301:Insect Hormones; D009419:Nerve Tissue Proteins; D011506:Proteins; C066819:sli protein, Drosophila