Recombinant Human Proprotein convertase subtilisin/kexin type 6 (PCSK6), partial

Function

Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues

Subcellular Location

Secreted

Tissue Specificity

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

Subunit

The PACE4A-I precursor protein seems to exist in the reticulum endoplasmic as both a monomer and a dimer-sized complex whereas mature PACE4A-I exists only as a monomer, suggesting that propeptide cleavage affects its tertiary or quaternary structure. Interacts (immature form including the propeptide) with RCN3; probably involved in the maturation and the secretion of PCSK6 (PubMed:16433634)

• Kiefer M.C. et al. Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15. — DNA Cell Biol. (1991)
• Tsuji A. et al. Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms. — Biochem. Biophys. Res. Commun. (1994)
• Tsuji A. et al. PubMed: 7980617 — Biochem. Biophys. Res. Commun. (1994)
• Mori K. et al. Identification of a novel PACE4 isoform, PACE4E. (SEP-)
• Mori K. et al. A novel human PACE4 isoform, PACE4E is an active processing protease containing a hydrophobic cluster at the carboxy terminus. — J. Biochem. (1997)
• Tsuji A. et al. Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease. — J. Biochem. (1997)
• Zhong M. et al. Functional analysis of human PACE4-A and PACE4-C isoforms: identification of a new PACE4-CS isoform. — FEBS Lett. (1996)
• Sucic J.F. et al. Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain. — Biochem. J. (1999)