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. 2001 Mar 15;354(Pt 3):689–695. doi: 10.1042/0264-6021:3540689

'Shed' furin: mapping of the cleavage determinants and identification of its C-terminus.

B Plaimauer 1, G Mohr 1, W Wernhart 1, M Himmelspach 1, F Dorner 1, U Schlokat 1
PMCID: PMC1221701  PMID: 11237874

Abstract

The human endoprotease furin is involved in the proteolytic maturation of the precursor molecules of a wide variety of bioactive proteins. Despite its localization in the membranes of the trans-Golgi system by means of a transmembrane domain, it has repeatedly been reported to form a C-terminally truncated, naturally secreted form referred to as 'shed' furin. In order to identify the cleavage site, internal deletion mutants of increasing size, N-terminal to Leu(708), and subsequently individual amino acid substitutions were introduced, and Arg(683) was identified as the prime determinant for shedding. MS analysis determined Ser(682) as the C-terminus of shed furin, suggesting that monobasic cleavage may occur N-terminal to Arg(683). Alteration of Arg(683) directs the shedding mechanism to alternative cleaving sites previously unused.

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Selected References

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