Summary: Glutaminase
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Glutaminase Edit Wikipedia article
| glutaminase | |||||||||
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| Crystallographic structure of dimeric protein-glutaminase from Chryseobacterium proteolyticum.[1] | |||||||||
| 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 | ||||||||
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| Glutaminase | |||||||||
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| 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 | ||||||||
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Glutaminase is an amidohydrolase enzyme which generates glutamate from glutamine. Glutaminase has tissue-specific isoenzymes. Importantly, glutaminase is found in glial cells.
Glutaminase catalyzes the following reaction:
Glutamine + H2O â Glutamate + NH3
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[edit] Tissue distribution
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]
[edit] Regulation
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 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 GLS2âs control of ROS levels facilitate âthe ability of p53 to protect cells from accumulation of genomic damage and allows cells to survive after mild and repairable genotoxic stress.â[4]
[edit] Structure
The structure of Glutaminase was determined using X-ray diffraction. The resolution of this protein is 1.73Ã . 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. 21%, or 95 residues, construct the 23 beta sheet strands.[1]
[edit] Isozymes
Humans express the following two glutaminase isozymes:
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[edit] 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).
[edit] References
- ^ 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.
- ^ 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): 38939â38944. PMID 12163477.
- ^ 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): 197â203. doi:10.1016/j.abb.2010.09.002. PMID 20831857.
- ^ 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): 7461â6. doi:10.1073/pnas.1002459107. PMC 2867754. PMID 20351271. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2867754/.
[edit] External links
- Glutaminase at the US National Library of Medicine Medical Subject Headings (MeSH)
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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
| PANDIT: | PF04960 |
| Pseudofam: | PF04960 |
| SCOP: | 1mki |
| SYSTERS: | Glutaminase |
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.
| Molecular function | glutaminase activity (GO:0004359) |
| Biological process | glutamine metabolic process (GO:0006541) |
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 contains the following 7 members:
Beta-lactamase Beta-lactamase2 DAP_B Glutaminase Peptidase_S11 Peptidase_S13 TranspeptidaseAlignments
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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| Seed (17) |
Full (2528) |
Representative proteomes | NCBI (1601) |
Meta (173) |
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| RP15 (146) |
RP35 (287) |
RP55 (427) |
RP75 (544) |
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| Jalview | ||||||||
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| PP/heatmap | 1 | |||||||
| Pfam viewer | ||||||||
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
| Seed (17) |
Full (2528) |
Representative proteomes | NCBI (1601) |
Meta (173) |
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| RP15 (146) |
RP35 (287) |
RP55 (427) |
RP75 (544) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
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.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
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
| 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
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 286 | ||||||||||||
| Family (HMM) version: | 10 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
GlutaminaseStructures
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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