Complete structure of the gene for human keratin 18

The complete sequence of the human keratin 18 (K18) gene was determined. The K18 gene is 3791 bp in length and the K18 protein is coded for by seven exons. The exon structure of K18 has been conserved compared to that of other keratin genes, with the exception of a single 3' terminal exon that codes for the tail domain of the protein that is represented by two exons in epidermal keratins. The K18 gene contains an unusual AG/GC donor splice site of intron 3 instead of the consensus AG/GT sequence. This variation is not seen in any other intermediate filament genes. The promoter region of the gene contains a TATA box, six potential SP1 binding sites, and 10 copies of CACCC boxes but lacks any CCAAT boxes and is surprisingly different from the immediately 5' flanking region of the homologous mouse Endo B gene. However, both genes contain small CpG islands surrounding the 5' end of exon 1 and, in addition, conserve repetitive Alu potential transcription units approximately 300 nt upstream of the transcriptional start site.