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We have isolated a human gastrin gene from a genomic library by employing a human gastrin cDNA clone as a hybridization probe. The total length of the gene is approximately 4.0 kilobase pairs, and the gene is separated into three exons and two introns. A 130-base-pair intron interrupts the coding region and a 3.0-kilobase-pair intron is located in the 5' untranslated region. Nucleotide sequence analysis showed that all of the exon-intron boundaries follow the A-G/G-T consensus sequences. A putative transcription initiation site is assigned to the adenine 60 nucleotides upstream from the exon-intron junction on the basis of S1 nuclease protection mapping. A possible "TATA" equivalent sequence T-T-A-T-A-A is located 28 base pairs upstream from the transcription initiation site. A "CAT box" sequence, C-A-T-T, is located 99 nucleotides upstream of the transcription initiation site. A poly(A)-addition signal, A-A-U-A-A-A, is located 80 base pairs downstream from the termination codon. Comparison of the nucleotide sequences of the human cDNA and the genomic clone revealed that the aspartic acid codon at position 71 of preprogastrin is interrupted by the small intron (130 base pairs). The 3' region of the large intron contains a sequence of 300 nucleotides that is flanked by 15-nucleotide direct repeats. This sequence exhibits a striking homology to the human Alu-type sequence.

Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence.