Insect gut carboxypeptidase-like, carboxypeptidase domain (IPR034223)

Short name: IGCP-like_CPD

Overlapping homologous superfamilies


Domain relationships


This entry represents the carboxypeptidase domain found in the insect gut carboxypeptidases that belong to the peptidase family M14, subfamily M14A [PMID: 8439290]. Insect gut carboxypeptidases (IGCP) help digest food proteins and are synthesized as zymogens [PMID: 11676544]. Unusually, IGCP2 releases C-terminal glutamates [PMID: 15128309]. These carboxypeptidases are often from agricultural pests and inhibition is seen as a possible means of pest control, however, an IGCP from tomato fruitworm (Helicoverpa zea) is insensitive to potato carboxypeptidase inhibitor [PMID: 16260742].

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.