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57  structures 1760  species 1  interaction 2528  sequences 25  architectures

Family: Glutaminase (PF04960)

Summary: Glutaminase

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Glutaminase Edit Wikipedia article

glutaminase
Glutaminase.png
Identifiers
EC number 3.5.1.2
CAS number 9001-47-2
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Glutaminase
PDB 2osu EBI.jpg
probable glutaminase from bacillus subtilis complexed with 6-diazo-5-oxo-l-norleucine
Identifiers
Symbol Glutaminase
Pfam PF04960
Pfam clan CL0013
InterPro IPR015868
SCOP 1mki
SUPERFAMILY 1mki

Glutaminase (EC 3.5.1.2, 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[edit]

Glutaminase is expressed in periportal hepatocytes, where it generates NH3 (ammonia) for urea synthesis, as does glutamate dehydrogenase. 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.[2]

Regulation[edit]

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.[3]

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.”[4]

Structure[edit]

The structure of Glutaminase was determined using X-ray diffraction. The resolution of this protein is 1.73 Å. Resolution measures the quality of the data that has been collected on the crystal containing the protein. There are 2 chains containing 305 residues that make up the length of this dimeric protein. On each strand, 23% of Glutaminase, or 71 residues, are found in the 8 helices. Twenty-one percent, or 95 residues, construct the 23 beta sheet strands.[1]

Isozymes[edit]

Humans express the following two glutaminase isozymes:

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

Related proteins[edit]

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).

References[edit]

  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. ^ 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. 
  3. ^ 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/j.abb.2010.09.002. PMID 20831857. 
  4. ^ 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. 

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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:3.5.1.2.

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 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).

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 7 members:

Beta-lactamase Beta-lactamase2 DAP_B Glutaminase Peptidase_S11 Peptidase_S13 Transpeptidase

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(17)
Full
(2528)
Representative proteomes NCBI
(1601)
Meta
(173)
RP15
(146)
RP35
(287)
RP55
(427)
RP75
(544)
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  Seed
(17)
Full
(2528)
Representative proteomes NCBI
(1601)
Meta
(173)
RP15
(146)
RP35
(287)
RP55
(427)
RP75
(544)
Alignment:
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  Seed
(17)
Full
(2528)
Representative proteomes NCBI
(1601)
Meta
(173)
RP15
(146)
RP35
(287)
RP55
(427)
RP75
(544)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

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

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: COG2066
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 17
Number in full: 2528
Average length of the domain: 277.00 aa
Average identity of full alignment: 43 %
Average coverage of the sequence by the domain: 80.87 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -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 19.3
Model length: 286
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Interactions

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Glutaminase

Structures

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 57 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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