GLS
GeneName
GLS
Summary
GLS, also known as GLS1 or glutaminase, is a 73 kDa enzyme that plays a vital role in the metabolism of glutamine, converting it into glutamate. It is predominantly expressed in the cytosol and mitochondrial matrix of various tissues, including the brain and liver. GLS is involved in several biological processes, such as glutamate biosynthesis and glutamine catabolism, and is critical for maintaining intracellular glutamate homeostasis. Additionally, it participates in chemical synaptic transmission and is implicated in processes like protein homotetramerization and the regulation of respiratory gaseous exchange by the nervous system.
Importance
GLS is relevant to: - Cancer metabolism, as it supports the growth of tumours by providing glutamate for energy production and biosynthesis - Neurological disorders, given its role in glutamate homeostasis which is essential for synaptic function - Metabolic disorders, due to its involvement in amino acid metabolism and energy homeostasis - Suckling behaviour in mammals, highlighting its physiological roles beyond metabolism
Top Products
For researchers investigating GLS, we highly recommend the top-selling recombinant antibody, Anti-Glutaminase antibody [EP7212] (ab156876). This antibody has been validated in knockout models and is particularly effective for Western blotting (WB), making it an excellent choice for those looking to study glutaminase with confidence. With 113 citations, it is well-regarded in the research community, reflecting its reliability and performance in various applications. This product offers the consistency and quality that researchers need for their experiments.
Abcam Product Citation Summary
The data indicates that the Abcam antibody ab156876 is frequently used to study GLS in various human cell lines, particularly in the context of cancer research, drug resistance, and metabolic processes. The antibody has been applied in both Western blotting and immunohistochemistry, highlighting its versatility in detecting GLS across different experimental setups.
Abcam Product Citation Table
Domain
The C-terminal ANK repeats prevent the assembly of the supra-tetrameric filaments.
A highly mobile activation loop at the dimer-dimer interface is important for enzyme activity.
Function
Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate, the main excitatory neurotransmitter in the brain (PubMed:30239721, PubMed:30575854, PubMed:30970188).
Isoform 2
Lacks catalytic activity.
Involvement in disease
Developmental and epileptic encephalopathy 71
DEE71
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE71 is an autosomal recessive form with onset at birth. Death occurs in first weeks of life.
None
The disease is caused by variants affecting the gene represented in this entry.
Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development
CASGID
An autosomal dominant disease characterized by infantile-onset cataract, erythematic subcutaneous nodules, profound developmental delay, self-injurious behavior, and intracerebral glutamate excess. Histopathologic analysis of skin lesions show deep perivascular and periglandular lymphohistiocytic infiltrates and pronounced leukocytoclasia at the surface of the dermis, focal vacuolar alterations, hyperkeratosis, and parakeratosis of the epidermis.
None
The disease is caused by variants affecting the gene represented in this entry.
Global developmental delay, progressive ataxia, and elevated glutamine
GDPAG
An autosomal recessive disease characterized by early-onset delay in motor skills, delayed speech, progressive ataxia, and neurologic deterioration. Plasma glutamine is persistently elevated by a factor of 2.5 despite normal plasma ammonia levels.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Synthesized as a 74-kDa cytosolic precursor which is proteolytically processed by the mitochondrial-processing peptidase (MPP) via a 72-kDa intermediate to yield the mature mitochondrial 68- and 65-kDa subunits.
Sequence Similarities
Belongs to the glutaminase family.
Tissue Specificity
Isoform 1 and isoform 3 are detected in brain cortex. Isoform 3 is highly expressed in astrocytoma, ganglioglioma and ependymoma. Isoform 1 is highly expressed in brain and kidney, but not detected in liver. Isoform 3 is highly expressed in heart and pancreas, detected at lower levels in placenta, lung, pancreas and kidney, but is not detected in liver. Isoform 2 is expressed in cardiac and skeletal muscle.
Cellular localization
- Isoform 1
- Mitochondrion
- Cytoplasm
- Cytosol
- The 74-kDa cytosolic precursor is translocated into the mitochondria and processed via a 72-kDa intermediate to yield the mature 68- and 65-kDa subunits.
- Isoform 3
- Mitochondrion
- Glutaminase kidney isoform, mitochondrial 68 kDa chain
- Mitochondrion matrix
- Produced by the proteolytic processing of the 74-kDa cytosolic precursor.
- Glutaminase kidney isoform, mitochondrial 65 kDa chain
- Mitochondrion matrix
- Produced by the proteolytic processing of the 74-kDa cytosolic precursor.
Alternative names
GLS1, KIAA0838, GLS, K-glutaminase, L-glutamine amidohydrolase
Database links
swissprot:O94925 entrezGene:2744 swissprot:O94925-3 omim:138280