| Activity |
|---|
| Catalytic type | Metallo |
| Peplist | Included in the Peplist with identifier PL00248 |
| NC-IUBMB | Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.17 (Metallocarboxypeptidases) >> Peptidase 3.4.17.21
|
| Enzymology | BRENDA database |
| Activity status | human: active (Carter & Coyle, 2004)
mouse: active (Bacich et al., 2001)
|
| Physiology | Thought to liberate glutamate from Ac-Asp-Glu in brain. Hydrolyses dietary pteroyl-polyglutamate in jejunum. Universally upregulated in the vasculature of solid tumors, and shown to play a role in angiogenesis (Conway et al., 2006). |
| Knockout | A human polymorphism is apparently associated with hyperhomocysteinemia (Devlin et al., 2000). According to one group, mice harbouring a disruption of the gene for glutamate carboxypeptidase II (Folh1) developed normally to adulthood, but were protected from peripheral neuropathy and ischemic brain injury (Bacich et al., 2002; Bacich et al., 2005). However, there is a separate report that homozygous null mice did not survive beyond embryonic day 8 (Tsai et al., 2003). |
| Pharmaceutical relevance | Has use in the diagnosis and assessment of prostatic carcinoma. Inhibitors may serve to target imaging agents or chemotherapeutic drugs to disseminated prostate cancer (Tang et al., 2003). Inhibitors introduced into the spine are reportedly analgesic (Yamamoto et al., 2001). An inhibitor has been found to provide effective neuroprotective treatment in a rat model of transient middle cerebral artery occlusion; given post-injury it reduced brain infarction and ameliorated the pathology associated with focal brain ischemia (Williams et al., 2001). Glutamate carboxypeptidase II inhibition may be of value in the treatment of amyotrophic lateral sclerosis (Ghadge et al., 2003). |
| Pathways |
KEGG | Vitamin digestion and absorption |
|
Other databases
| TREEFAM | http://www.treefam.org/family/TF312981 |
| Cleavage site specificity |
Explanations of how to interpret the
following cleavage site sequence logo and specificity matrix can be found here. |
|---|
| Cleavage pattern | -/-/-/Eda E/-/-/- (based on 10 cleavages) |
