A gene has been isolated from an activated human T cell cDNA library that encodes a novel, 35 kD phosphorylated GTP-binding protein (designated GEM) that demonstrates approximately 20 percent homology to c-Ha-ras. GEM contains approximately 10 kD of unique ser/thr rich sequence on the amino terminus and 7 kD of unique sequence, rich in basic amino acids, on the carboxy terminus. GEM has been shown to preferentially bind GTP over ATP. GEM expression is highly regulated. GEM RNA and protein are transiently expressed in mid-G1 following mitogenic activation of T cells and fibroblasts. GEM PNA is expressed in several different murine tissues of hematopoietic and non-hematopoietic origins. Transfected and endogenously expressed GEM has been shown to localize to the inner face of the plasma membrane, and to cytoplasmic vesicles in neuronal cells. In addition to the GTP-binding domain, the carboxy but not amino terminus is required for membrane localization. The GTP-binding property of GEM, in addition to its identification as a phosphorylation substrate and membrane-associated protein, suggest a role in signal transduction.