Paired Basic Amino acid residue-Cleaving Enzyme-4 (PACE4, proprotein convertase subtilisin/kexin type 6, PCSK6, subtilisin-like proprotein convertase 4, SPC4)

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Function

endoprotease activity within the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine & non-neuroendocrine tissues
capable of cleavage at the RX(K/R)R consensus motif
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

propeptide domain acts as an intramolecular chaperone assisting folding of zymogen within the endoplasmic reticulum
isoform PACE4D lacks the propeptide domain belongs to the peptidase S8 family
PACE4A-I precursor protein seems to exist in the endoplasmic reticulum as both a monomer & a dimer
mature PACE4A-I exists only as a monomer, suggesting that propeptide cleavage affects its tertiary or quaternary structure
contains 1 homo B/P domain
contains 1 PLAC domain

isoform PACE4A-I, PACE4A-II, PACE4B: secreted
isoform PACE4C, PACE4CS: endoplasmic reticulum not secreted, remains probably in zymogen form in endoplasmic reticulum
isoform PACE4E-I, PACE4E-II: intracytoplasmic membrane retained intracellularly probably through a hydrophobic cluster in their C-terminus

PACE4B, PACE4C, PACE4CS, PACE4D probably enzymatically inactive

each PACE4 isoform exhibits a unique restricted distribution
PACE4A-I is expressed in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, but at comparatively higher levels in the liver
PACE4A-II is at least expressed in placenta
PACE4B was only found in the embryonic kidney cell line from which it was isolated
PACE4C & PACE4D are expressed in placenta
PACE4E-I is expressed in cerebellum, placenta & pituitary
PACE4E-II is at least present in cerebellum