Domain

Carboxypeptidase B, carboxypeptidase domain (IPR034253)

Short name: CPB_M14_CPD

Overlapping homologous superfamilies

None.

Domain relationships

Description

This entry represents the carboxypeptidase domain found in carboxypeptidase B-like peptidases. Carboxypeptidase B (CPB; MEROPS identifier M14.003) belongs to subfamily M14A (A/B subfamily) of the M14 family of metallocarboxypeptidases (MCPs) [PMID: 7674922]. Carboxypeptidase B (CPB) releases the basic residues lysine or arginine [PMID: 507824]. A/B subfamily enzymes are normally synthesized as inactive precursors containing a signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases [PMID: 1989878]. Procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs where it is activated by trypsin [PMID: 2018774]. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients [PMID: 11167870].

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.
CDD