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64  structures 7256  species 1  interaction 10084  sequences 39  architectures

Family: Glutaminase (PF04960)

Summary: Glutaminase

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This is the Wikipedia entry entitled "Glutaminase". More...

Glutaminase Edit Wikipedia article

EC number
CAS number 9001-47-2
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
PDB 2osu EBI.jpg
probable glutaminase from bacillus subtilis complexed with 6-diazo-5-oxo-l-norleucine
Symbol Glutaminase
Pfam PF04960
Pfam clan CL0013
InterPro IPR015868
SCOP 1mki

Glutaminase (EC, glutaminase I, L-glutaminase, glutamine aminohydrolase) is an amidohydrolase enzyme that generates glutamate from glutamine. Glutaminase has tissue-specific isoenzymes. Glutaminase has an important role in glial cells.

Glutaminase catalyzes the following reaction:

Glutamine + H2O → Glutamate + NH3

Tissue distribution

Glutaminase is expressed and active in periportal hepatocytes, where it generates NH3 (ammonia) for urea synthesis, as does glutamate dehydrogenase.[2] Glutaminase is also expressed in the epithelial cells of the renal tubules, where the produced ammonia is excreted as ammonium ions. This excretion of ammonium ions is an important mechanism of renal acid-base regulation. During chronic acidosis, glutaminase is induced in the kidney, which leads to an increase in the amount of ammonium ions excreted. Glutaminase can also be found in the intestines, whereby hepatic portal ammonia can reach as high as 0.26 mM (compared to an arterial blood ammonia of 0.02 mM).

One of the most important roles of glutaminase is found in the axonal terminals of neurons in the central nervous system. Glutamate is the most abundantly used excitatory neurotransmitter in the CNS. After being released into the synapse for neurotransmission, glutamate is rapidly taken up by nearby astrocytes, which convert it to glutamine. This glutamine is then supplied to the presynaptic terminals of the neurons, where glutaminases convert it back to glutamate for loading into synaptic vesicles. Although both "kidney-type" (GLS1) and "liver-type" (GLS2) glutaminases are expressed in brain, GLS2 has been reported to exist only in cellular nuclei in CNS neurons.[3]


ADP is the strongest adenine nucleotide activator of glutaminase. Studies have also suggested ADP lowered the K(m) for glutamine and increased the V(max). They found that these effects were increased even more when ATP was present.[4]

Phosphate-activated mitochondrial glutaminase (GLS2) is suggested to be linked with elevated metabolism, decreased intracellular reactive oxygen species (ROS) levels, and overall decreased DNA oxidation in both normal and stressed cells. It is suggested that GLS2’s control of ROS levels facilitates “the ability of p53 to protect cells from accumulation of genomic damage and allows cells to survive after mild and repairable genotoxic stress.”[5]


The structure of Glutaminase has been determined using X-ray diffraction to a resolution of up to 1.73 Ã…. There are 2 chains containing 305 residues that make up the length of this dimeric protein. On each strand, 23% of the amino acid content, or 71 residues, are found in the 8 helices. Twenty-one percent, or 95 residues, make up the 23 beta sheet strands.[1]


Humans express 4 isoforms of glutaminase. GLS1 encodes 2 types of kidney-type glutaminase with a high activity and low Km. GLS2 encodes 2 forms of liver-type glutaminase with a low activity and allosteric regulation.[2]

Symbol GLS1
Entrez 2744
HUGO 4331
OMIM 138280
RefSeq NM_014905
UniProt O94925
Other data
EC number
Locus Chr. 2 q32-q34
glutaminase 2
(liver, mitochondrial)
Symbol GLS2
Entrez 27165
HUGO 29570
OMIM 606365
RefSeq NM_013267
UniProt Q9UI32
Other data
EC number
Locus Chr. 12 q13

Related proteins

Glutaminases belong to a larger family that includes serine-dependent beta-lactamases and penicillin-binding proteins. Many bacteria have two isozymes. This model is based on selected known glutaminases and their homologs within prokaryotes, with the exclusion of highly derived (long-branch) and architecturally varied homologs, so as to achieve conservative assignments. A sharp drop in scores occurs below 250, and cutoffs are set accordingly. The enzyme converts glutamine to glutamate, with the release of ammonia. Members tend to be described as glutaminase A (glsA), where B (glsB) is unknown and may not be homologous (as in Rhizobium etli; some species have two isozymes that may both be designated A (GlsA1 and GlsA2).


  1. ^ a b PDB 3A56; Hashizume R, Mizutani K, Takahashi N, Matsubara H, Matsunaga A, Yamaguchi S, Mikami B (2010). "Crystal structure of protein-glutaminase". to be published. doi:10.2210/pdb3a56/pdb. 
  2. ^ a b Van Noorden, Botman (August 2014). "Determination of Phosphate-activated Glutaminase Activity and Its Kinetics in Mouse Tissues using Metabolic Mapping (Quantitative Enzyme Histochemistry)" (PDF). Journal of Histochemistry & Cytochemistry 62: 813–26. doi:10.1369/0022155414551177. PMID 25163927. Retrieved 26 September 2014. 
  3. ^ Olalla L, Gutiérrez A, Campos JA, Khan ZU, Alonso FJ, Segura JA, Márquez J, Aledo JC (Aug 2002). "Nuclear localization of L-type glutaminase in mammalian brain". J. Biol. Chem. 277 (41): 38939–38944. doi:10.1074/jbc.C200373200. PMID 12163477. 
  4. ^ Masola B, Ngubane NP (December 2010). "The activity of phosphate-dependent glutaminase from the rat small intestine is modulated by ADP and is dependent on integrity of mitochondria". Arch. Biochem. Biophys. 504 (2): 197–203. doi:10.1016/ PMID 20831857. 
  5. ^ Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I, Prives C (April 2010). "Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species". Proc. Natl. Acad. Sci. U.S.A. 107 (16): 7461–6. doi:10.1073/pnas.1002459107. PMC 2867754. PMID 20351271. 

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Glutaminase Provide feedback

This family of enzymes deaminates glutamine to glutamate EC:

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR015868

Glutaminases (EC) deaminate glutamine to glutamate. In Bacillus subtilis, glutaminase is encoded by glnA, which is part of an operon, glnA-glnT (formerly ybgJ-ybgH), where glnT encodes a glutamine transporter. The glnA-glnT operon is regulated by the 2-component system GlnK-GlnL in response to glutamine [PUBMED:15995196]. This entry represents the core structural motif of a family of glutaminases that include GlnA, which are characterised by their beta-lactamase-like topology, containing a cluster of alpha-helices and an alpha/beta sandwich.

This family describes the enzyme glutaminase, from a larger family that includes serine-dependent beta-lactamases and penicillin-binding proteins. Many bacteria have two isozymes. This model is based on selected known glutaminases and their homologues within prokaryotes, with the exclusion of highly-derived (long branch) and architecturally varied homologues, so as to achieve conservative assignments. A sharp drop in scores occurs below 250, and cutoffs are set accordingly. The enzyme converts glutamine to glutamate, with the release of ammonia. Members tend to be described as glutaminase A (glsA), where B (glsB) is unknown and may not be homologous (as in Rhizobium etli. Some species have two isozymes that may both be designated A (GlsA1 and GlsA2).

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Beta-lactamase (CL0013), which has the following description:

This superfamily contains proteins that have a beta-lactamase fold. This includes beta-lactamases as well as Dala-Dala carboxypeptidases and glutaminases.

The clan contains the following 6 members:

Beta-lactamase Beta-lactamase2 Glutaminase Peptidase_S11 Peptidase_S13 Transpeptidase


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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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Curation and family details

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Seed source: COG2066
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 326
Number in full: 10084
Average length of the domain: 278.70 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 84.99 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.8 19.8
Trusted cut-off 19.8 19.8
Noise cut-off 19.7 19.7
Model length: 286
Family (HMM) version: 11
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Species distribution

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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Glutaminase domain has been found. There are 64 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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