A novel GTP-binding protein which is selectively repressed in SV40 transformed fibroblasts.

We have used a subtractive hybridization procedure to isolate cDNA clones for proteins that are produced by human fibroblasts, but not by their SV40-transformed counterparts. With this technique we found, in addition to fibronectin and collagen VI, a novel GTP-binding protein. Sequencing of overlapping cDNA clones demonstrated that this protein is composed of 364 amino acids with a molecular mass of 41 kDa and a calculated isoelectric point of 9.4. It contains the five sequence motifs G1-G5 that are conserved in all GTP-binding proteins. Apart from these characteristic motifs the amino acid sequence differs substantially from those of the well characterized G-proteins, but it is similar to those of some recently identified proteins from Caenorhabditis elegans, from Schizosaccharomyces pombe, and from an archaebacterium, suggesting the existence of a new subfamily within the superfamily of the GTP-binding proteins. The striking conservation of the primary structure between distantly related species indicates a fundamental function of the new protein. Since it is produced in normal, but not in virally transformed fibroblasts, it may play a role in the expression of the transformed phenotype or in growth control.