Domain

Peptidase M13, C-terminal domain (IPR018497)

Short name: Peptidase_M13_C

Domain relationships

None.

Description

This entry represents the C-terminal domain of M13 peptidases.

This group of metallopeptidases belong to the MEROPS peptidase family M13 (neprilysin family, clan MA(E)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH [PMID: 7674922].

M13 peptidases are well-studied proteases found in a wide range of organisms including mammals and bacteria. In mammals they participate in processes such as cardiovascular development, blood-pressure regulation, nervous control of respiration, and regulation of the function of neuropeptides in the central nervous system. In bacteria they may be used for digestion of milk [PMID: 11223883, PMID: 7674922]. The family includes eukaryotic and prokaryotic oligopeptidases, as well as some of the proteins responsible for the molecular basis of the blood group antigens e.g. Kell [PMID: 7674922].

Neprilysin (EC:3.4.24.11), is another member of this group, it is variously known as common acute lymphoblastic leukemia antigen (CALLA), enkephalinase (gp100) and neutral endopeptidase metalloendopeptidase (NEP). It is a plasma membrane-bound mammalian enzyme that is able to digest biologically-active peptides, including enkephalins [PMID: 7674922]. The zinc ligands of neprilysin are known and are analogous to those in thermolysin, a related peptidase [PMID: 7674922, PMID: 8099556]. Neprilysins, like thermolysin, are inhibited by phosphoramidon, which appears to selectively inhibit this family in mammals. The enzymes are all oligopeptidases, digesting oligo- and polypeptides, but not proteins [PMID: 7674922]. Neprilysin consists of a short cytoplasmic domain, a membrane-spanning region and a large extracellular domain. The cytoplasmic domain contains a conformationally-restrained octapeptide, which is thought to act as a stop transfer sequence that prevents proteolysis and secretion [PMID: 7674922, PMID: 3555489].

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0004222 metalloendopeptidase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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