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Literature summary for 3.4.24.B10 extracted from

  • Loechel, F.; Overgaard, M.T.; Oxvig, C.; Albrechtsen, R.; Wewer, U.M.
    Regulation of human ADAM 12 protease by the prodomain. Evidence for a functional cysteine switch (1999), J. Biol. Chem., 274, 13427-13433.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
transient expression in COS-7 cells of the enzyme mutants, secretion to the medium Homo sapiens

Protein Variants

Protein Variants Comment Organism
C179A site-directed mutagenesis, exchange of the cysteine-switch residue of the prodomain, still active in complex formation with alpha2-macroglobulin Homo sapiens
C179H site-directed mutagenesis, exchange of the cysteine-switch residue of the prodomain, still active in complex formation with alpha2-macroglobulin Homo sapiens
C179H/E351Q site-directed mutagenesis, exchange of the cysteine-switch residue of the prodomain results in a no longer latent but inactive zymogen Homo sapiens
C179S site-directed mutagenesis, exchange of the cysteine-switch residue of the prodomain the glutamic acid residue and of the zinc binding domain involved in catalytic activity, inactive to form complexes with alpha2-macroglobulin, results in a no longer latent but inactive zymogen Homo sapiens
additional information KR207NG mutation prevents cleavage of the prodomain by furin, construction of enzyme mutants where the prodomain or the metalloprotease domain or both are eliminated or exchanged for an Ig kappa-chain leader sequence, secretion to the medium, inactive mutant Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1,10-phenanthroline
-
Homo sapiens
hydroxamate inhibitor BB-94 slight inhibition Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ metalloprotease domain is the catalytically active site Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens enzyme complexes alpha2-macroglobulin ?
-
?
protein + H2O Homo sapiens
-
peptides
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens O43184
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein degylcosylation with endoglycosidase H Homo sapiens
proteolytic modification the cysteine-switch of the prodomain maintaines the zymogen in a latent state, enzyme is synthesized as a catalytically inactive zymogen, in vivo cleavage by a furin-like endopeptidase, autoactivation is possible with N-ethylmaleimide Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information enzyme complexes alpha2-macroglobulin Homo sapiens ?
-
?
protein + H2O
-
Homo sapiens peptides
-
?

Synonyms

Synonyms Comment Organism
a disintegrin and metalloproteinase domain 12
-
Homo sapiens
ADAM12
-
Homo sapiens
M12.212 Merops-ID Homo sapiens
meltrin alpha
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens