This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]
Function:
Likely to represent an endoprotease activity within the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues and capable of cleavage at the RX(K/R)R consensus motif.
Subcellular Location:
Secreted; Endomembrane system. Retained intracellularly probably through a hydrophobic cluster in their SLCterminus and Endoplasmic reticulum. Not secreted, remains probably in zymogen form in endoplasmic reticulum.
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.
Post-translational modifications:
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.
Similarity:
Belongs to the peptidase S8 family.
Contains 1 homo B/P domain.
Contains 1 PLAC domain.
SWISS:
P29122
Gene ID:
5046
Database links:
Entrez Gene: 524684 Cow
Entrez Gene: 488703 Dog
Entrez Gene: 100673009 Elephant
Entrez Gene: 100057677 Horse
Entrez Gene: 5046 Human
Entrez Gene: 100405129 Marmoset (common)
Entrez Gene: 18553 Mouse
Entrez Gene: 100020955 Opossum
Entrez Gene: 100152144 Pig
Entrez Gene: 25507 Rat
Omim: 167405 Human
SwissProt: P29122 Human
SwissProt: Q63415 Rat
Unigene: 498494 Human
Unigene: 665989 Human
Unigene: 950 Rat
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Sample:Cerebrum(Mouse)Lysate at 40 ug
Primary: Anti-PACE4(SL19997R)at 1/300 dilution
Secondary: IRDye800CW Goat Anti-RabbitIgG at 1/20000 dilution
Predicted band size: 91kD
Observed band size: 91kD
Sample:Heart (Mouse)Lysate at 40 ug
Primary: Anti-PACE4(SL19997R)at 1/300 dilution
Secondary: IRDye800CW Goat Anti-RabbitIgG at 1/20000 dilution
Predicted band size: 91kD
Observed band size: 91kD
Paraformaldehyde-fixed, paraffin embedded (Rat brain); Antigen retrieval by boiling in sodium citrate buffer (pH6.0) for 15min; Block endogenous peroxidase by 3% hydrogen peroxide for 20 minutes; Blocking buffer (normal goat serum) at 37°C for 30min; Antibody incubation with (PACE4) Polyclonal Antibody, Unconjugated (SL19997R) at 1:400 overnight at 4°C, followed by operating according to SP Kit(Rabbit) (sp-0023) instructionsand DAB staining.
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