Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68.
The gld-1 gene of Caenorhabditis elegans is a germ-line-specific tumor suppressor gene that is essential for oogenesis. We have cloned the gld-1 gene and find that it encodes two proteins that differ by 3 amino acids. The predicted proteins contain a approximately 170-amino-acid region that we term the GSG domain (GRP33/Sam68/GLD-1), on the basis of significant similarity between GLD-1, GRP33 from shrimp, and the Src-associated protein Sam68 from mouse (also described as GAPap62 from humans). A conserved structural motif called the KH domain is found within the larger GSG domain, suggesting a biochemical function for GLD-1 protein in binding RNA. The importance of the GSG domain to the function of gld-1 in vivo is revealed by mutations that affect 5 different conserved GSG domain residues. These include missense mutations in an absolutely conserved residue of the KH domain that eliminate the tumor suppressor function of gld-1.
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Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002107:Caenorhabditis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000737:chemistry*; D012734:Disorders of Sex Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D016147:Genes, Tumor Suppressor; D015801:Helminth Proteins / Q000235:genetics* / Q000502:physiology; D007301:Insect Hormones / Q000737:chemistry; D019476:Insect Proteins; D008297:Male; D008938:Mitosis / Q000235:genetics; D008969:Molecular Sequence Data; D009866:Oogenesis / Q000235:genetics; D010750:Phosphoproteins / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013091:Spermatogenesis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D014960:X Chromosome
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C489561:Dok1 protein, mouse; C074561:GAP-associated protein p62; C094448:GLD-1 protein, C elegans; C053819:GRP33 protein, Artemia salina; D015801:Helminth Proteins; D007301:Insect Hormones; D019476:Insect Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins