Fibrillin C-terminal processing

Stable Identifier
R-HSA-2129357
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Extracellular deposition of fibrillin requires removal of the C-terminus, which can be cleaved in vitro by several furin/PACE family convertases (Raghunath et al. 1999, Ritty et al. 1999) in a process that is inhibited by N-glycosylation and calreticulin (Ashworth et al. 1999). Furin (PACE) is a transmembrane protein, synthesized as a 100 kDa protein, which rapidly undergoes autocatalytic cleavage to a 94 kDa protein in the endoplasmic reticulum (ER). The propeptide remains bound as an auto-inhibitor. Propeptide release occurs in the acidic pH of the trans-golgi-network (TGN)/endosomal compartment, activating furin. Though furin is primarily localized to the TGN a proportion of furin molecules are found on the cell surface (Teuchert et al. 1999). Profibrillin-1 processing does not occur in the TGN, where it is bound by two ER-resident molecular chaperones, BiP and GRP94. Instead activation by furin occurs as profibrillin-1 is secreted, or immediately after secretion (Wallis et al. 2003).
Literature References
PubMed ID Title Journal Year
10198291 Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by PACE/furin-like activity required for incorporation in the matrix

Raghunath, M, Milewicz, DM, Hamstra, D, Rehemtulla, A, Peters, R, Park, ES, Putnam, EA, Ritty, T, Tschödrich-Rotter, M

J Cell Sci 1999
Participants
Participates
Catalyst Activity

serine-type endopeptidase activity of FURIN [plasma membrane]

Orthologous Events
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