The genomic structure of the gene encoding human pan-leukocyte surface glycoprotein CD53 (a member of the "tetraspan family" of membrane proteins) was determined. The gene consists of eight exons encoding all sequences found in cDNA and is spread over more than 26 kilobases of genomic DNA. The exon-intron organization of the CD53 gene is strikingly similar to the CD63 and TAPA-1 genes, which suggests a close evolutionary relationship between these genes. The 5' end of the gene upstream of the first exon contains at least three close transcription start points (approximately 20 base pairs 5' of the 5' end of the published cDNA). The region upstream of the transcription initiation sites is not G+C rich; it contains potential binding sites for several transcriptional factors but no TATA or CCAAT boxes.