3.4.17.21: Glutamate carboxypeptidase II

This is an abbreviated version!
For detailed information about Glutamate carboxypeptidase II, go to the full flat file.

Reaction

release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates =

Synonyms

100 kDa ileum brush border membrane protein, Acetylaspartylglutamate dipeptidase, altered meristem program1, AMP1, Dipeptidase, acetylaspartylglutamate, EC 3.4.19.8, FGCP, folate hydrolase, folate hydrolase 1, FOLH1, Folylpoly-gamma-glutamate carboxypeptidase, folylpoly-gamma-glutamate carboxypeptidase II, GCP II, GCPII, GCPIII, glutamate carboxypeptidase, glutamate carboxypeptidase II, glutamate carboxypeptidase III, GPCPII, I100, Ileal dipeptidylpeptidase, Membrane glutamate carboxypeptidase, mGCP, More, N-acetyl-alpha-linked acidic dipeptidase, N-acetyl-alpha-linked acidic dipeptidase I, N-acetylaspartylglutamate peptidase, N-acetylated alpha-linked acid dipeptidase, N-Acetylated alpha-linked acidic dipeptidase, N-Acetylated-alpha-linked acidic dipeptidase, N-acetylated-alpha-linked acidic dipeptidase 2, N-acetylated-alpha-linked acidic dipeptidase II, N-Acetylated-alpha-linked-acidic dipeptidase, N-acetylated-alpha-linked-acidic-dipeptidase, N-Acetylated-alpha-linked-amino dipeptidase, NAADLADase, NAADLADse, NAAG degradation enzyme, NAAG peptidase, NAAG peptidase II, NAAG-hydrolyzing activity, NAALA dipeptidase, NAALADase, Naaladase I, NAALADase II, NLD I, PMSA, prostate specific membrane antigen, Prostate-specific membrane antigen, Prostate-specific membrane antigen homolog, prostate-specificmembrane antigen, Prostrate-specific membrane antigen, PSM, PSM antigen, PSMA, Pteroylpoly-gamma-glutamate carboxypeptidase, Rat NAAG peptidase

ECTree

     3 Hydrolases

         3.4 Acting on peptide bonds (peptidases)

             3.4.17 Metallocarboxypeptidases

                3.4.17.21 Glutamate carboxypeptidase II

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Results	in table
1	Activating Compound
189	AA Sequence
40	Application
1	CAS Registry Number
25	Cloned(Commentary)
12	Crystallization (Commentary)
7461	Disease/ Diagnostics
5	Expression
9	General Information
3	General Stability
121	IC50 Value
374	Inhibitors
4	kcat/KM [mM/s]
108	Ki Value [mM]
15	KM Value [mM]
83	Localization
41	Metals/Ions
8	Molecular Weight [Da]
62	Natural Substrates/ Products (Substrates)
128	Organism
2	Pathway
90	PDB ID
15	pH Optimum
2	pH Range
17	Posttranslational Modification
37	Protein Variants
14	Purification (Commentary)
4	Reaction
7	Reaction Type
126	Reference
230	Source Tissue
10	Specific Activity [micromol/min/mg]
144	Substrates and Products (Substrate)
10	Subunits
261	Synonyms
14	Temperature Optimum [°C]
1	Temperature Range [°C]
6	Turnover Number [1/s]

Natural Substrates Products

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Natural Substrates Products on EC 3.4.17.21 - Glutamate carboxypeptidase II

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NATURAL SUBSTRATE

NATURAL PRODUCT

REACTION DIAGRAM

ORGANISM

UNIPROT

COMMENTARY
(Substrate)

LITERATURE
(Substrate)

COMMENTARY
(Product)

LITERATURE
(Product)

REVERSIBILITY
r=reversible
ir=irreversible
?=not specified

folyl-poly-gamma-glutamate + H2O

?

Homo sapiens

-

cleavage of the C-terminal glutamate

683948

-

-

?

N-acetyl-alpha L-aspartyl-L-glutamate + H2O

N-acetyl-L-aspartate + L-glutamate

Mus musculus

-

-

701258

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

24 entries

N-acetyl-Asp-Glu + H2O

N-acetyl-Asp + Glu

3 entries

N-Acetyl-L-Asp-L-Glu + H2O

?

3 entries

N-acetyl-L-aspartyl-L-glutamate + H2O

L-glutamate + N-acetyl-L-aspartate

3 entries

N-acetyl-L-aspartyl-L-glutamate + H2O

N-acetyl-L-aspartate + L-glutamate

4 entries

poly-gamma-glutamate folate + H2O

?

2 entries

additional information

?

-

7 entries

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Canis lupus familiaris

-

-

670740

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

-

-

656468, 668484, 668866, 669506, 669776, 670397, 670740

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

Q04609

-

670685

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

-

i.e. NAAG, a neurodipeptide, the enzyme acts as membrane-bound receptor being recycled through clathrin coated pits, expression regulation within cells and involvement in prostate cancer and metastasis, overview

669595

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

-

supply of the primary excitatory neurotransmitter glutamate, the enzyme is involved in neurological disorders, and neuropathic and inflammatory pain

670363

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

-

the enzyme is involved in glutamate-mediated neurodegenerative disorders, enzyme inhibition is a mechanism for reduction of excitotoxic glutamate

667114

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

-

the enzyme is involved in suppressing prostate cancer invasiveness

668154

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

-

the enzyme is responsible for cleavage of NAAG to yield free glutamate

670817

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Homo sapiens

Q04609

the essential enzyme is involved in prostate cancer, stroke, amyotrophic lateral sclerosis, and neuropathic pain

668408

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Macaca fascicularis

-

-

670740

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Macaca mulatta

-

-

670740

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Mus musculus

-

-

670406, 670740

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Mus musculus

-

i.e. NAAG, a neurodipeptide, the enzyme acts as membrane-bound receptor being recycled through clathrin coated pits, expression regulation within cells in prostate cancer and metastasis, overview

669595

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Mus musculus

Q9CZR2

the enzyme inactivates the neurotransmitter in the synaptic cleft

669923

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Mus musculus

-

the enzyme is responsible for glutamate supply, enzyme inhibition decreases the glutamate and increases the N-acetyl-alpha-L-aspartyl-L-glutamate concentration in the brain, which can be a method to treat opioid tolerance and diminish effects of morphine withdrawal, overview

670857

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Mus musculus C57/Bl

-

the enzyme is responsible for glutamate supply, enzyme inhibition decreases the glutamate and increases the N-acetyl-alpha-L-aspartyl-L-glutamate concentration in the brain, which can be a method to treat opioid tolerance and diminish effects of morphine withdrawal, overview

670857

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Procambarus clarkii

-

enzyme regulation is mediated by glial glutamate and acetylcholine receptors in the nervous tissue

669932

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Rattus norvegicus

-

-

668484, 668486, 669776, 670406

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Rattus norvegicus

-

enzyme inhibition reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion traumatic brain injury

669962

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Rattus norvegicus

-

i.e. NAAG, a neurodipeptide, the enzyme acts as membrane-bound receptor being recycled through clathrin coated pits, expression regulation within cells in prostate cancer and metastasis, overview

669595

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Rattus norvegicus

-

i.e. NAAG, a presynaptically active endogenous neuropeptide which is cleaved by the enzyme in the extracellular space

669943

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Rattus norvegicus

-

NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats

669962

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Rattus norvegicus

-

supply of the primary excitatory neurotransmitter glutamate

670363

-

-

?

N-acetyl-alpha-L-aspartyl-L-glutamate + H2O

N-acetyl-alpha-L-aspartate + L-glutamate

Rattus norvegicus

-

the enzyme is involved in glutamate-mediated neurodegenerative disorders, enzyme inhibition is a mechanism for reduction of excitotoxic glutamate

667114

-

-

?

N-acetyl-Asp-Glu + H2O

N-acetyl-Asp + Glu

Homo sapiens

-

-

683948

-

-

?

N-acetyl-Asp-Glu + H2O

N-acetyl-Asp + Glu

Rattus norvegicus

-

-

655290, 657162

-

-

?

N-acetyl-Asp-Glu + H2O

N-acetyl-Asp + Glu

Rattus norvegicus

-

the enzyme converts N-acetylaspartylglutamate from a neuroprotectant to a neurotoxin

656609

-

-

?

N-Acetyl-L-Asp-L-Glu + H2O

?

Homo sapiens

-

functions as a cell surface peptidase, possibly hydrolzing peptides in prostatic fluid

137214

-

-

?

N-Acetyl-L-Asp-L-Glu + H2O

?

Rattus norvegicus

-

may play a role in signaling between non-myelinating Schwann cells and peripheral axons

137221

-

-

?

N-Acetyl-L-Asp-L-Glu + H2O

?

Rattus norvegicus

-

role in synaptic peptide degradation

137228

-

-

?

N-acetyl-L-aspartyl-L-glutamate + H2O

L-glutamate + N-acetyl-L-aspartate

Homo sapiens

-

-

707124, 708479, 710007

-

-

?

N-acetyl-L-aspartyl-L-glutamate + H2O

L-glutamate + N-acetyl-L-aspartate

Homo sapiens

-

NAALADase, a neuropeptidase that produces the neurotransmitter glutamate and N-acetyl-Laspartate throught hydrolysis of N-acetyl-L-aspartyl-L-glutamate

709440

-

-

?

N-acetyl-L-aspartyl-L-glutamate + H2O

L-glutamate + N-acetyl-L-aspartate

Rattus norvegicus

-

-

708400, 709605

-

-

?

N-acetyl-L-aspartyl-L-glutamate + H2O

N-acetyl-L-aspartate + L-glutamate

Homo sapiens

-

-

701206

-

-

?

N-acetyl-L-aspartyl-L-glutamate + H2O

N-acetyl-L-aspartate + L-glutamate

Homo sapiens

Q04609

-

696330, 699452

-

-

?

N-acetyl-L-aspartyl-L-glutamate + H2O

N-acetyl-L-aspartate + L-glutamate

Homo sapiens

-

-

699452

-

-

?

N-acetyl-L-aspartyl-L-glutamate + H2O

N-acetyl-L-aspartate + L-glutamate

Rattus norvegicus

-

-

698502

-

-

?

poly-gamma-glutamate folate + H2O

?

Homo sapiens

-

activity outside of the cell

669595

-

-

?

poly-gamma-glutamate folate + H2O

?

Mus musculus

-

activity outside of the cell

669595

-

-

?

additional information

?

-

Homo sapiens

-

the enzyme interacts with filamin leading to internalization of PMSA into cells in the perinuclear region, overview

669595

-

-

?

additional information

?

-

Homo sapiens

-

intestinal absorption of polyglutamyl folates involves cleavage of the glutamate side chain by FGCP

697394

-

-

?

additional information

?

-

Homo sapiens

-

cross-linking of cell surface PSMA with specific antibodies activates the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 in prostate carcinoma LNCaP cells via NF-kappaB activation, overview. Proliferation of LNCaP cells is inducible by interleukin-6, CCL5 or by cross-linking of PSMA

710358

-

-

?

additional information

?

-

Homo sapiens

-

PSMA is highly homologous to N-acetylated alpha-linked acidic dipeptidase, NAALADase

709440

-

-

?

additional information

?

-

Homo sapiens

-

PSMA-targeted photodynamic therapy on cytoskeletal networks in prostate cancer cells results in rapid disruption of microtubules (alpha-/beta-tubulin), microfilaments (actin), and intermediate filaments (cytokeratin 8/18) in the cytoplasm of LNCaP cells. The collapse of cytoplasmic microtubules and the later nuclear translocation of alpha-/beta-tubulin are the most dramatic alternation, overview

707973

-

-

?

additional information

?

-

Mus musculus

-

the enzyme interacts with filamin leading to internalization of PMSA into cells in the perinuclear region, overview

669595

-

-

?

additional information

?

-

Rattus norvegicus

-

enzyme inhibition depresses mossy fiber-CA3 synaptic transmission

669943

-

-

?