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. 1996 Jul 1;317(Pt 1):45–50. doi: 10.1042/bj3170045

Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types.

L Howard 1, X Lu 1, S Mitchell 1, S Griffiths 1, P Glynn 1
PMCID: PMC1217484  PMID: 8694785

Abstract

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.

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Selected References

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  1. Bjarnason J. B., Fox J. W. Snake venom metalloendopeptidases: reprolysins. Methods Enzymol. 1995;248:345–368. doi: 10.1016/0076-6879(95)48023-4. [DOI] [PubMed] [Google Scholar]
  2. Blobel C. P., Myles D. G., Primakoff P., White J. M. Proteolytic processing of a protein involved in sperm-egg fusion correlates with acquisition of fertilization competence. J Cell Biol. 1990 Jul;111(1):69–78. doi: 10.1083/jcb.111.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blobel C. P., Wolfsberg T. G., Turck C. W., Myles D. G., Primakoff P., White J. M. A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature. 1992 Mar 19;356(6366):248–252. doi: 10.1038/356248a0. [DOI] [PubMed] [Google Scholar]
  4. Bode W., Gomis-Rüth F. X., Stöckler W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the 'metzincins'. FEBS Lett. 1993 Sep 27;331(1-2):134–140. doi: 10.1016/0014-5793(93)80312-i. [DOI] [PubMed] [Google Scholar]
  5. Chantry A., Earl C., Groome N., Glynn P. Metalloendoprotease cleavage of 18.2- and 14.1-kilodalton basic proteins dissociating from rodent myelin membranes generates 10.0- and 5.9-kilodalton C-terminal fragments. J Neurochem. 1988 Mar;50(3):688–694. doi: 10.1111/j.1471-4159.1988.tb02968.x. [DOI] [PubMed] [Google Scholar]
  6. Chantry A., Glynn P. A novel metalloproteinase originally isolated from brain myelin membranes is present in many tissues. Biochem J. 1990 May 15;268(1):245–248. doi: 10.1042/bj2680245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chantry A., Gregson N. A., Glynn P. A novel metalloproteinase associated with brain myelin membranes. Isolation and characterization. J Biol Chem. 1989 Dec 25;264(36):21603–21607. [PubMed] [Google Scholar]
  8. Dumermuth E., Sterchi E. E., Jiang W. P., Wolz R. L., Bond J. S., Flannery A. V., Beynon R. J. The astacin family of metalloendopeptidases. J Biol Chem. 1991 Nov 15;266(32):21381–21385. [PubMed] [Google Scholar]
  9. Emi M., Katagiri T., Harada Y., Saito H., Inazawa J., Ito I., Kasumi F., Nakamura Y. A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers. Nat Genet. 1993 Oct;5(2):151–157. doi: 10.1038/ng1093-151. [DOI] [PubMed] [Google Scholar]
  10. Grams F., Huber R., Kress L. F., Moroder L., Bode W. Activation of snake venom metalloproteinases by a cysteine switch-like mechanism. FEBS Lett. 1993 Nov 29;335(1):76–80. doi: 10.1016/0014-5793(93)80443-x. [DOI] [PubMed] [Google Scholar]
  11. Halban P. A., Irminger J. C. Sorting and processing of secretory proteins. Biochem J. 1994 Apr 1;299(Pt 1):1–18. doi: 10.1042/bj2990001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jackson A. P., Seow H. F., Holmes N., Drickamer K., Parham P. Clathrin light chains contain brain-specific insertion sequences and a region of homology with intermediate filaments. Nature. 1987 Mar 12;326(6109):154–159. doi: 10.1038/326154a0. [DOI] [PubMed] [Google Scholar]
  13. Jiang W., Bond J. S. Families of metalloendopeptidases and their relationships. FEBS Lett. 1992 Nov 9;312(2-3):110–114. doi: 10.1016/0014-5793(92)80916-5. [DOI] [PubMed] [Google Scholar]
  14. Jiang W., Gorbea C. M., Flannery A. V., Beynon R. J., Grant G. A., Bond J. S. The alpha subunit of meprin A. Molecular cloning and sequencing, differential expression in inbred mouse strains, and evidence for divergent evolution of the alpha and beta subunits. J Biol Chem. 1992 May 5;267(13):9185–9193. [PubMed] [Google Scholar]
  15. Katagiri T., Harada Y., Emi M., Nakamura Y. Human metalloprotease/disintegrin-like (MDC) gene: exon-intron organization and alternative splicing. Cytogenet Cell Genet. 1995;68(1-2):39–44. doi: 10.1159/000133884. [DOI] [PubMed] [Google Scholar]
  16. Kini R. M., Evans H. J. Structural domains in venom proteins: evidence that metalloproteinases and nonenzymatic platelet aggregation inhibitors (disintegrins) from snake venoms are derived by proteolysis from a common precursor. Toxicon. 1992 Mar;30(3):265–293. doi: 10.1016/0041-0101(92)90869-7. [DOI] [PubMed] [Google Scholar]
  17. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  18. Matrisian L. M. The matrix-degrading metalloproteinases. Bioessays. 1992 Jul;14(7):455–463. doi: 10.1002/bies.950140705. [DOI] [PubMed] [Google Scholar]
  19. Paine M. J., Desmond H. P., Theakston R. D., Crampton J. M. Purification, cloning, and molecular characterization of a high molecular weight hemorrhagic metalloprotease, jararhagin, from Bothrops jararaca venom. Insights into the disintegrin gene family. J Biol Chem. 1992 Nov 15;267(32):22869–22876. [PubMed] [Google Scholar]
  20. Pei D., Weiss S. J. Furin-dependent intracellular activation of the human stromelysin-3 zymogen. Nature. 1995 May 18;375(6528):244–247. doi: 10.1038/375244a0. [DOI] [PubMed] [Google Scholar]
  21. Perry A. C., Jones R., Barker P. J., Hall L. A mammalian epididymal protein with remarkable sequence similarity to snake venom haemorrhagic peptides. Biochem J. 1992 Sep 15;286(Pt 3):671–675. doi: 10.1042/bj2860671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rawlings N. D., Barrett A. J. Evolutionary families of metallopeptidases. Methods Enzymol. 1995;248:183–228. doi: 10.1016/0076-6879(95)48015-3. [DOI] [PubMed] [Google Scholar]
  23. Roques B. P., Noble F., Daugé V., Fournié-Zaluski M. C., Beaumont A. Neutral endopeptidase 24.11: structure, inhibition, and experimental and clinical pharmacology. Pharmacol Rev. 1993 Mar;45(1):87–146. [PubMed] [Google Scholar]
  24. Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., Seiki M. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994 Jul 7;370(6484):61–65. doi: 10.1038/370061a0. [DOI] [PubMed] [Google Scholar]
  25. Sheets M. D., Ogg S. C., Wickens M. P. Point mutations in AAUAAA and the poly (A) addition site: effects on the accuracy and efficiency of cleavage and polyadenylation in vitro. Nucleic Acids Res. 1990 Oct 11;18(19):5799–5805. doi: 10.1093/nar/18.19.5799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shimada K., Takahashi M., Tanzawa K. Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells. J Biol Chem. 1994 Jul 15;269(28):18275–18278. [PubMed] [Google Scholar]
  27. Smeekens S. P. Processing of protein precursors by a novel family of subtilisin-related mammalian endoproteases. Biotechnology (N Y) 1993 Feb;11(2):182–186. doi: 10.1038/nbt0293-182. [DOI] [PubMed] [Google Scholar]
  28. Van Wart H. E., Birkedal-Hansen H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5578–5582. doi: 10.1073/pnas.87.14.5578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wolfsberg T. G., Bazan J. F., Blobel C. P., Myles D. G., Primakoff P., White J. M. The precursor region of a protein active in sperm-egg fusion contains a metalloprotease and a disintegrin domain: structural, functional, and evolutionary implications. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10783–10787. doi: 10.1073/pnas.90.22.10783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yagami-Hiromasa T., Sato T., Kurisaki T., Kamijo K., Nabeshima Y., Fujisawa-Sehara A. A metalloprotease-disintegrin participating in myoblast fusion. Nature. 1995 Oct 19;377(6550):652–656. doi: 10.1038/377652a0. [DOI] [PubMed] [Google Scholar]
  31. Yoshida S., Setoguchi M., Higuchi Y., Akizuki S., Yamamoto S. Molecular cloning of cDNA encoding MS2 antigen, a novel cell surface antigen strongly expressed in murine monocytic lineage. Int Immunol. 1990;2(6):585–591. doi: 10.1093/intimm/2.6.585. [DOI] [PubMed] [Google Scholar]

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