| Activity |
| Catalytic type | Metallo |
| Peplist | Included in the Peplist with identifier PL00213 |
| NC-IUBMB | Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.17 (Metallocarboxypeptidases) >> Peptidase 3.4.17.20
|
| Enzymology | BRENDA database |
| Activity | A carboxypeptidase. |
| Proteolytic events | CutDB database (3 cleavages) |
| Activity status | human: active (Hendriks, 2004) mouse: active (Marx et al., 2000)
|
| Physiology | Has anti-fibrinolytic activity, removing C-terminal lysine residues of partially degraded fibrin that are important in plasmin formation mediated by t-plasminogen activator (S01.232) (Marx, 2004). May also degradate bioactive peptides in the circulation. A splice variant of carboxypeptidase U has been termed 'brain carboxypeptidase B' and attributed a physiological role in the degradation of beta-amyloid 1-42 (Matsumoto et al., 2000). It is reported that the Thr325Ile dimorphism in carboxypeptidase U affects the outcome of meningococcal disease (Kremer Hovinga et al., 2004). Genetic variation in carboxypeptidase U reported to be associated with the risk of splanchnic vein thrombosis (de Bruijne et al., 2007). |
| Knockout | Mice deficient in carboxypeptidase U (termed carboxypeptidase R) showed increased sensitivity to a combined challenge with lipopolysaccharide and cobra venom factor that wild-type mice were able to survive (Asai et al., 2004). |
| Pharmaceutical relevance | Inhibitors of carboxypeptidase U have been reported to enhance endogenous fibrinolysis and reduce thrombi in a tissue factor-induced microthrombosis model (Muto et al., 2003). Such inhibitors therefore have potential use in antithrombotic and thrombolytic therapy (Barrow et al., 2003). |
| Pathways |
KEGG | Complement and coagulation cascades |
|
KEGG | Pancreatic secretion |
|
KEGG | Protein digestion and absorption |
|
Other databases
| TREEFAM | http://www.treefam.org/family/TF317197 |
| Cleavage site specificity |
Explanations of how to interpret the
following cleavage site sequence logo and specificity matrix can be found here. |
| Cleavage pattern | -/-/l/- KR/-/-/- (based on 19 cleavages) |