Carboxypeptidase M (CPM)

Carboxypeptidase M (CPM) is a membrane-bound, zinc-dependent exopeptidase that selectively removes C-terminal basic residues—predominantly arginine and lysine—from a variety of peptide substrates, including peptide hormones, chemokines, kinins (e.g., bradykinin), and other regulatory peptides[1][2][3]. CPM’s activity modulates the biological function of these peptides, affecting processes like inflammation, cell signaling, and hormone regulation[1][2]. It is widely expressed on the surface of multiple cell types—particularly hematopoietic and stromal cells—and can also exist in soluble form in body fluids[2]. CPM plays a critical role in the regulation of the kallikrein–kinin system, contributing to the generation of des-Arg derivatives that are agonists for the kinin B1 receptor. In addition to its enzymatic activity, CPM can act as a positive allosteric modulator of the B1 receptor via direct protein-protein interactions, enhancing receptor signaling even when catalytically inactive[2]. CPM gene expression and polymorphisms have been linked to cancer (notably as a diagnostic marker in well-differentiated liposarcoma), inflammation, and psychiatric disorders such as major depressive disorder[1]. The enzyme is regarded as a potential but not (as of now) a widely exploited therapeutic target in these diseases[1][2][3].

Other names

Carboxypeptidase MCPMrenal carboxypeptidaseurinary carboxypeptidase B

Enzymatic cleavage of C-terminal arginine/lysine from peptide hormones, chemokines, kinins, and other signaling peptides, modifying their activity - Allosteric modulation of the kinin B1 receptor by direct interaction, enhancing or modulating receptor signaling, sometimes independently of enzymatic activity[2]