AEBP1/CPX, carboxypeptidase domain (IPR034243)

Short name: AEBP1/CPX_M14_CPD

Overlapping homologous superfamilies


Domain relationships


This entry represents the carboxypeptidase domain found in non-peptidase homologues of the metallocarboxypeptidase (MCP) family M14, subfamily M14B (N/E subfamily) [PMID: 7674922], including the misnamed carboxypeptidases X (CPX, MEROPS identifiers M14.952; M14.953; M14.954) [PMID: 10073577, PMID: 9809751] and adipocyte-enhancer binding protein 1 (AEBP1; M14.951).

CPX-1,CPX-2 and AEBP1/ACLP are inactive towards standard MCP substrates because they lack one or more critical active site and substrate-binding residues that are necessary for activity [PMID: 10073577, PMID: 11766880]. They may function as binding proteins rather than as active MCPs or display catalytic activity toward other substrates. They also contain an N-terminal discoidin domain [PMID: 16538615].

AEBP1 is a truncated form of aortic carboxypeptidase-like protein (ACLP), which may arise from alternative splicing of the gene. The MCP domain is important for the function of AEBP1 as a transcriptional repressor [PMID: 16538615]. AEBP1 is involved in several biological processes including adipogenesis, macrophage cholesterol homeostasis, and inflammation. In macrophages, AEBP1 promotes the expression of IL-6, TNF-alpha, MCP-1, and iNOS whose expression is tightly regulated by NF-kappaB activity. ACLP, a secreted protein that associates with the extracellular matrix, is essential for abdominal wall development and contributes to dermal wound healing [PMID: 12660896, PMID: 16538615].

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.