Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Proprotein convertase subtilisin/kexin type 4 (PACE4) is a human subtilisin-like serine protease.
• Previous research identified PACE4, but its various isoforms and their functions remain incompletely understood.

Purpose of the Study:

• To isolate and characterize novel complementary DNA (cDNA) sequences encoding PACE4 isoforms.
• To investigate the structural differences between these novel isoforms and the previously identified PACE4.
• To determine the presence of these isoforms in other species.

Main Methods:

• Isolation of cDNA clones from human placenta and rat pituitary cDNA libraries.
• Sequence analysis of isolated cDNAs to deduce protein sequences.
• Comparison of deduced protein sequences with known PACE4 sequences.

Main Results:

• Two novel PACE4 isoforms, PACE4C and PACE4D, were isolated from human placenta.
• PACE4C protein (652 amino acids) lacks the carboxy-terminal cysteine-rich region found in PACE4.
• PACE4D protein (497 amino acids) lacks a signal peptide, propeptide, and cysteine-rich region.
• Homologous cDNAs for these isoforms were also found in the rat pituitary library.

Conclusions:

• The discovery of PACE4C and PACE4D reveals new structural variations of the PACE4 protease.
• These structural differences, particularly the absence of specific domains, suggest that PACE4C and PACE4D may possess distinct enzymatic activities or cellular localizations.
• The presence of these isoforms in both human and rat suggests conserved biological roles.