furin (Paired Basic Amino acid residue-Cleaving Enzyme {PACE}, kexin homolog, paired-basic endopeptidase, prohormone-processing endoprotease, serine proteinase homolog fur)

Function: - ubiquitous endoprotease within constitutive secretory pathways - capable of cleavage at the RX(K/R)R consensus motif - interacts with FLNA (putative) - binds to PACS1 which mediates TGN localization & connection to clathrin adapters - could be inhibited by the not secondly cleaved propeptide; the inhibition peptide, which plays the role of an intramolecular chaperone, is autocatalytically removed in the endoplasmic reticulum (ER) & remains non-covalently bound to furin as a potent autoinhibitor; following transport to the trans Golgi, a second cleavage within the inhibition propeptide results in propeptide dissociation & furin activation - phosphorylation is required for TGN localization of the endoprotease. - in vivo, exists as di-, mono- & non-phosphorylated forms - release of mature proteins from their proproteins by cleavage of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid & Yaa is Arg or Lys - releases albumin, complement component C3 & von Willebrand factor from their respective precursors Cofactor: Ca⁺² Structure: - contains a cytoplasmic domain responsible for its TGN localization & recycling from the cell surface - belongs to the peptidase S8 family, Furin subfamily - contains 1 homo B/P domain Compartment: - Golgi, trans-Golgi network membrane - cell membrane - shuttles between the trans-Golgi network & the cell surface - propeptide cleavage is a prerequisite for exit of furin molecules out of the endoplasmic reticulum (ER, a second cleavage within the propeptide occurs in the trans Golgi network (TGN), followed by the release of the propeptide & activation of furin Expression: seems to be expressed ubiquitously

Properties

SIZE: entity length = 794 aa MW = 87 kD COMPARTMENT: plasma membrane golgi MOTIF: signal sequence {1-24} proteolytic site {75-76} proteolytic site {107-108} Ca+2-binding site SITE: 115-115 aspartate residue {D153} Ca+2-binding site SITE: 162-162 histidine residue {H194} Ca+2-binding site SITE: 208-208 cysteine residue {C211} MODIFICATION: cysteine residue {C360} Ca+2-binding site SITE: 258-258 Ca+2-binding site SITE: 301-301 cysteine residue {C303} MODIFICATION: cysteine residue {C333} Ca+2-binding site SITE: 331-331 cysteine residue {C333} MODIFICATION: cysteine residue {C303} cysteine residue {C360} MODIFICATION: cysteine residue {C211} serine residue {S368} N-glycosylation site {N387} N-glycosylation site {N440} cysteine residue {C450} MODIFICATION: cysteine residue {C474} cysteine residue {C474} MODIFICATION: cysteine residue {C450} Cell attachment site {498-500} N-glycosylation site {N553} cysteine-rich region {556-705} transmembrane domain {716-738} Cell surface signal {759-762} Trans Golgi network signal {773-779} MOTIF: Ser phosphorylation site {S773} Ser phosphorylation site {S775}

Database Correlations

OMIM 136950 UniProt P09958 PFAM correlations Kegg hsa:5045 ENZYME 3.4.21.75