CLONING AND CHARACTERIZATION OF THE HUMAN TARTRATE-RESISTANT ACID-PHOSPHATASE (TRAP) GENE

The expression and protein structure of the tartrate-resistant acid ph osphatase (TRAP), an iron-containing lysosomal glycoprotein in cells o f the mononuclear phagocyte system, have been analyzed extensively in the past. In some diseases, like hairy cell leukemia and Gaucher's dis ease, cytochemically detected TRAP expression is used as a disease-ass ociated marker. In this paper we describe the isolation of a genomic c osmid clone of the human TRAP gene. Restriction mapping revealed a 22- kb insert and the complete genomic structure of the TRAP gene. A 6-kb HindIII-fragment harboring the entire TRAP gene was subcloned and the 5'-flanking region of 3026 bp was sequenced. Analysis of the sequence data showed the presence of potential transcription factor binding sit es. Two transcriptional start sites were identified in the untranslate d exon 1 at positions -349 and -347 bp relative to the translational s tart codon. Linked to a luciferase-encoding reporter gene the 5'-flank ing region was sufficient to direct transcription in the heterologous cell line BHK-21. Treatment of the transfected cells with different mo dulators of the intracellular iron content showed that regulation of T RAP expression is dependent on iron. In summary, these data imply a po ssible functional role of the TRAP gene product either in the storage or the transport of iron.