The human gene for diamine oxidase, an amiloride binding protein. Molecular cloning, sequencing, and characterization of the promoter.

The amiloride binding protein (ABP) is detected in many epithelium-rich and/or hematopoietic tissues (Lingueglia, E., Renard, S., Voilley, N., Waldmann, R., Chassande, O., Lazdunski, M., and Barbry, P. (1993) Eur. J. Biochem. 216, 679-687). The protein binds amiloride and some of its derivatives, such as phenamil, benzamil, and ethylpropylamiloride. These properties have previously suggested that ABP might be associated with an amiloride-sensitive Na+ channel. It corresponds in fact to an amiloride-sensitive diamine oxidase (DAO) that catalyzes the degradation of compounds such as putrescine or histamine. The analysis of the organization of the sequence of the human ABP/DAO gene reveals that the 2.4-kilobase messenger RNA is transcribed from two close origins identifying the proximal promoter. After sequencing, some corrections within the initial cDNA sequence have been made. Human ABP/DAO corresponds to a 751-residue polypeptide. The promoter activity of 1800 base pairs upstream of the transcription start sites of the long form has been analyzed. Two bulks of cis-activating sequences have been identified. One of them constitutes the proximal promoter. It contains a palindromic sequence previously described as E-PAL. This motif is essential for the full activity of the promoter and behaves like a composite element. This first molecular cloning of a human gene coding for a diamine oxidase will allow us to further understand its regulation during cell growth and/or embryonic development.