We isolated and characterized human genomic clones encompassing the gene for the a-subunit of Giz, a GTP-binding signal transduction protein abundantly expressed in myeloid cells. The gene is divided into 9 exons and spans 23.5 kb. Exons 2, 6 and 7 encode putative guanine nucleotide-binding domains that are highly conserved among GTP-binding proteins. A polyadenylation signal located within exon 9 predicts an mRNA size (_ 2.3 kb) several hundred bases longer than that of published cDNAs, and consistent with the size seen on RNA blot hybridization. Primer extension and S, nuclease analysis determined a major and several minor transcriptional start sites. The first exon and 5' flanking region are highly G + C rich, contain several GC boxes (SPl transcription factor binding sites), a CAAT box, and lack a TATA box. The presumptive promoter region is thus similar to that of rap and other widely expressed genes.