Characterization of the cDNA and gene for mouse tumour necrosis factor α converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25

Numerous proteins are cleaved or 'shed' from their membrane-bound form. One such protein, tumour necrosis factor α (TNF-α), is synthesized as a type 2 transmembrane protein. Recently, a human protease responsible for this shedding, the TNF-α converting enzyme (TACE/ ADAM17), was isolated. TACE/ADAM17 is a member of the adamalysin class of zinc-binding metalloproteases or ADAM (a disintegrin and metalloprotease). We report the isolation and characterization of the mouse TACE/ADAM17 cDNA and gene. Mouse TACE/ADAM17 has a 92% amino-acid identity with the human protein and was ubiquitously expressed. A recombinant form of the protease is found to cleave a peptide representing the cleavage site of precursor mouse TNF-α. An alternatively spliced form of mouse TACE/ADAM17 was found that would produce a soluble protein. The gene for TACE/ADAM17 is approximately 50 kb and contains 19 exons. Chromosomal mapping places TACE/ADAM17 on mouse chromosome 12 and human chromosome 2p25.