Characterization of the cDNA and gene for mouse tumour necrosis factor alpha 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 alpha (TNF-alpha), is synthesized as a type 2 transmembrane protein. Recently, a human protease responsible for this shedding, the TNF-alpha converting enzyme (TACE/ADAM17), was isolated. TACE/ADAM17 is a member of the adamalysin class of zinc-binding metallopro teases or ADAM (a disintegrin and metalloprotease). We report the isolation and characterization of the mouse TACE/ADAM17 cDNA and gene, Mouse TACE/AD AM17 has a 92% amino-acid identity with the human protein and was ubiquitou sly expressed. A recombinant form of the protease is found to cleave a pept ide representing the cleavage site of precursor mouse TNF-alpha.An alternat ively spliced form of mouse TACE/ADAM17 was found that would produce a solu ble protein. The gene for TACE/ADAM17 is approximately 50 kb and contains 1 9 exons, Chromosomal mapping places TACE/ADAM17 on mouse chromosome 12 and human chromosome 2p25. (C) 1999 Academic Press.