PROSITE documentation PDOC52035
Peptidase family M14 domain profile


Carboxypeptidases (CPs) hydrolyse peptide bonds in target proteins to release C-terminal amino acids. These enzymes have been classified into different families according to sequence similarity, mechanism and function. One of the largest groups, carrying a single catalytic Zn(2+) in the active site, is the M14 family. This is divided into four subfamilies known as M14A, M14B, M14C and M14D. In general, M14A and M14B carboxypeptidases either function within the secretory pathway or are themselves secreted. The members of the M14A subfamily are produced as pro-enzymes that are activated following the cleavage of N-terminal segments. The M14B subfamily are produced as active enzymes with a transthyretin-like domain at the C-terminus. The M14C group consists of bacterial enzymes related to γ-D-glutamyl-(L)-meso-diaminopimelate peptidase I and process components of the bacterial cell wall. Like their M14A relatives, they also carry an N-terminal extension. Members of the M14D subfamily are referred to as cytosolic carboxypeptidases (CCPs) to reflect their cellular location [1,2,3].

The M14 family metallocarboxypeptidase domain displays an α/β/α sandwich structure with a central mixed parallel-antiparallel β sheet flanked on both sides by several helices (see <PDB:2C1C>). The active site is located at the basis of a deep groove and consists of a distorted tetrahedral Zn(2+) coordination site (a pair of histidines, a glutamate, and a coordinated water molecule) surrounded by catalytic residues that stabilize intermediates during hydrolysis. A Glu residue polarizes the nucleophilic water and donates a hydrogen to the leaving amine [1,2,3].

The profile we developed covers the entire peptidase family M14 domain.

Last update:

August 2023 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

PEPTIDASE_M14, PS52035; Peptidase family M14 domain profile  (MATRIX)


1AuthorsOtero A. Rodriguez de la Vega M. Tanco S. Lorenzo J. Aviles F.X. Reverter D.
TitleThe novel structure of a cytosolic M14 metallocarboxypeptidase (CCP) from Pseudomonas aeruginosa: a model for mammalian CCPs.
SourceFASEB. J. 26:3754-3764(2012).
PubMed ID22645247

2AuthorsRimsa V. Eadsforth T.C. Joosten R.P. Hunter W.N.
TitleHigh-resolution structure of the M14-type cytosolic carboxypeptidase from Burkholderia cenocepacia refined exploiting PDB_REDO strategies.
SourceActa Crystallogr. D. Biol. Crystallogr. 70:279-289(2014).
PubMed ID24531462

3AuthorsFeld G.K. El-Etr S. Corzett M.H. Hunter M.S. Belhocine K. Monack D.M. Frank M. Segelke B.W. Rasley A.
TitleStructure and function of REP34 implicates carboxypeptidase activity in Francisella tularensis host cell invasion.
SourceJ. Biol. Chem. 289:30668-30679(2014).
PubMed ID25231992

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