PACE4

Domain

The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum. Isoform PACE4D lacks the propeptide domain.

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.

Sequence similarities

Belongs to the peptidase S8 family.

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.

Cellular localization

• Isoform PACE4A-I
• Secreted
• Isoform PACE4A-II
• Secreted
• Isoform PACE4C
• Endoplasmic reticulum
• Not secreted, remains probably in zymogen form in endoplasmic reticulum.
• Isoform PACE4CS
• Endoplasmic reticulum
• Not secreted, remains probably in zymogen form in endoplasmic reticulum.
• Isoform PACE4E-I
• Endomembrane system
• Peripheral membrane protein
• Retained intracellularly probably through a hydrophobic cluster in their C-terminus.
• Isoform PACE4E-II
• Endomembrane system
• Peripheral membrane protein
• Retained intracellularly probably through a hydrophobic cluster in their C-terminus.
• Isoform PACE4B
• Secreted

Alternative names

• Proprotein convertase subtilisin/kexin type 6
• Paired basic amino acid cleaving enzyme 4
• Subtilisin-like proprotein convertase 4
• Subtilisin/kexin-like protease PACE4
• SPC4
• PACE4
• PCSK6

Database links

• entrezGene:5046
• omim:167405
• swissprot:P29122

Target type

Proteins

Molecular weight

106420Da