Metallocarboxypeptidase Z, carboxypeptidase domain (IPR034239)

Short name: M14_CPZ_CPD

Overlapping homologous superfamilies


Domain relationships


This entry represents the carboxypeptidase domain (CPD) found in carboxypeptidase Z. Carboxypeptidase Z (CPZ; MEROPS identifier M14.012) belongs to subfamily M14B (N/E subfamily) of the M14 family of metallocarboxypeptidases (MCPs) [PMID: 7674922]. CPZ is a secreted Zn-dependent enzyme whose biological function is largely unknown. Unlike other members of the N/E subfamily, CPZ has a bipartite structure, which consists of an N-terminal cysteine-rich domain (CRD) whose sequence is similar to Wnt-binding proteins, and a C-terminal CP catalytic domain that removes C-terminal Arg residues from substrates. CPZ is enriched in the extracellular matrix and is widely distributed during early embryogenesis [PMID: 11287206, PMID: 10671522]. That the CRD of CPZ can bind to Wnt4 suggests that CPZ plays a role in Wnt signaling [PMID: 11766880, PMID: 12944424].

The carboxypeptidase A family can be divided into four subfamilies: M14A (carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) [PMID: 7674922, PMID: 17244818]. Members of subfamily M14B have longer C-termini than those of subfamily M14A [PMID: 1449602], and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble [PMID: 7674922]. The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif [PMID: 7674922, PMID: 6887246]. Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended alpha-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts [PMID: 7674922, PMID: 1548696].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.