Summary for peptidase M28.010: glutamate carboxypeptidase II

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Nameglutamate carboxypeptidase II
Other namesN-acetylated-alpha-linked-acidic dipeptidase, acidic dipeptidase, GCPII, membrane glutamate carboxypeptidase, microsomal gamma-glutamyl carboxypeptidase, NAAG peptidase, pteroylpoly-gamma-glutamate carboxypeptidase, prostate-specific membrane antigen, PSMA, NAALADase
Domain architecture
MEROPS Classification
Classification Clan MH >> Subclan (none) >> Family M28 >> Subfamily B >> M28.010
Holotypeglutamate carboxypeptidase II (Homo sapiens), Uniprot accession Q04609 (peptidase unit: 291-576), MERNUM MER0002104
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00248
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.17 (Metallocarboxypeptidases) >> Peptidase 3.4.17.21
EnzymologyBRENDA database
Activity statushuman: active (Carter & Coyle, 2004)
mouse: active (Bacich et al., 2001)
PhysiologyThought 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).
KnockoutA 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 relevanceHas 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 KEGGVitamin digestion and absorption
Other databases TREEFAMhttp://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-/-/-/EdaScissile bondE/-/-/- (based on 10 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 0 0 0 0 0 0 0 0
Pro 0 0 0 0 0 0 0 0
Ala 0 0 0 2 0 0 0 0
Val 0 0 0 0 0 0 0 0
Leu 0 0 0 0 0 0 0 0
Ile 0 0 0 0 0 0 0 0
Met 0 0 0 0 2 0 0 0
Phe 0 0 0 0 0 0 0 0
Tyr 0 0 0 0 0 0 0 0
Trp 0 0 0 0 0 0 0 0
Ser 0 0 0 0 0 0 0 0
Thr 0 0 0 0 0 0 0 0
Cys 0 0 0 0 0 0 0 0
Asn 0 0 0 0 0 0 0 0
Gln 0 0 0 0 0 0 0 0
Asp 0 0 0 3 0 0 0 0
Glu 0 0 0 5 8 0 0 0
Lys 0 0 0 0 0 0 0 0
Arg 0 0 0 0 0 0 0 0
His 0 0 0 0 0 0 0 0
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
FOLH1 11p11.2 ENSG00000086205 2346 FOLH1 600934
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Folh1 7:D1-D2 ENSMUSG00000001773 53320 MGI:1858193