Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types.
A peptide sequence of a metalloprotease purified from bovine brain [Chantry, Gregson and Glynn (1989) J. Biol. Chem. 264, 21603-21607] was used to design an oligonucleotide probe for screening a bovine brain cDNA library. A contig of the two overlapping cDNA clones that were isolated encoded a 748-amino-acid polypeptide with similarity to the disintegrin-metalloprotease precursor proteins of haemorrhagic snake venom. The bovine protein has been named MADM, for mammalian disintegrin-metalloprotease. The predicted mature protein has 534 amino acids arrayed as extracellular metallo-protease and disintegrin (potential integrin-binding) domains, a transmembrane helix and a basic/proline-rich cytoplasmic C-terminus. Highly conserved homologues of bovine MADM were found in cDNA libraries of rat brain and a human U937 histiocytic lymphoma cell line. A wide variety of mammalian cell lines expressed low levels of MADM mRNA (4.5 and 3.2 kb transcripts) and mature polypeptide (M(r) 62000), as assessed by Northern analysis and Western blotting with an antiserum raised to a peptide within the disintegrin domain. MADM appears to be a rather distantly related member of the reprolysin protein family, which includes both the snake venom disintegrin-metalloproteases and a number of predicted cell-surface disintegrin-containing mammalian proteins.
Howard
L
L
Medical Research Council Toxicology Unit, University of Leicester, U.K.
Lu
X
X
Mitchell
S
S
Griffiths
S
S
Glynn
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002417:Cattle; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D019483:Disintegrins; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D019483:Disintegrins; D010455:Peptides; D011498:Protein Precursors; D008666:Metalloendopeptidases