Property Summary

NCBI Gene PubMed Count 69
PubMed Score 716.88
PubTator Score 146.61

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (35)

Disease log2 FC p
nephrosclerosis -1.036 5.3e-03
gastric cancer 1.100 5.9e-03
malignant mesothelioma -3.500 1.1e-07
astrocytoma -2.700 2.4e-03
ependymoma -3.500 1.2e-24
oligodendroglioma -2.400 3.5e-21
esophageal adenocarcinoma 1.200 2.3e-02
cutaneous lupus erythematosus 1.200 5.2e-04
psoriasis -3.200 1.8e-05
glioblastoma -3.200 8.5e-08
osteosarcoma 3.859 1.4e-05
medulloblastoma -3.100 1.8e-11
atypical teratoid / rhabdoid tumor -3.400 2.0e-12
medulloblastoma, large-cell 3.200 5.2e-06
primitive neuroectodermal tumor -2.400 4.7e-04
autosomal dominant Emery-Dreifuss muscul... 1.058 1.9e-03
juvenile dermatomyositis 1.112 2.2e-09
Atopic dermatitis 1.300 2.5e-04
tuberculosis -1.200 3.6e-06
non-small cell lung cancer -1.322 6.0e-09
lung cancer -3.100 3.8e-05
active Crohn's disease -1.229 8.2e-03
interstitial cystitis 1.200 5.8e-04
pediatric high grade glioma -2.900 3.0e-09
pilocytic astrocytoma -2.800 6.2e-12
aldosterone-producing adenoma -1.509 2.4e-02
subependymal giant cell astrocytoma -2.236 3.3e-02
nasopharyngeal carcinoma 1.600 1.2e-03
lung carcinoma -1.400 2.6e-19
Alzheimer's disease -1.400 3.5e-02
Pick disease -2.500 1.1e-03
ulcerative colitis -1.300 1.3e-03
ovarian cancer -3.600 4.3e-14
pituitary cancer 1.200 7.1e-04
dermatomyositis 1.100 1.1e-02

 GO Function (1)

Protein-protein Interaction (5)

MLP Assay (4)

AID Type Active / Inconclusive / Inactive Description
624146 confirmatory 105 / 173 / 1002 qHTS for Inhibitors of Glutaminase (GLS): LOPAC Validation
624154 summary 0 / 0 / 0 qHTS for Inhibitors of Glutaminase (GLS): Summary
624170 confirmatory 846 / 6744 / 401810 qHTS for Inhibitors of Glutaminase (GLS)
624261 confirmatory 5 / 14 / 17 qHTS for Inhibitors of Glutaminase (GLS): Hit Confirmation

Gene RIF (50)

PMID Text
27089238 Findings indicate a role for transcription factor c-Jun as a driver of cancer cell metabolic reprogramming, and suggest that cancers overexpressing JUN may be especially sensitive to glutaminase (GLS)-targeted therapies.
26710269 GLS1 was identified as a potential downstream target of the miR-192/-204-HOTTIP axis in hepatocellular carcinoma.
26575584 Data suggest that glutaminase C (GAC) inhibition maybe a potential treatment strategy for acquired erlotinib-resistant non-small cell lung cancer (NSCLC).
26134042 In the present study it was determined whether three key enzymes for glycolysis, glutaminolysis and de novo synthesis of FAs, hexokinase-2, glutaminase and fatty acid synthase
25915584 studies demonstrate that GLS is required for tumorigenesis and support small molecule and genetic inhibition of GLS as potential approaches for targeting the tumor cell-autonomous dependence on GLS for cancer therapy.
25880019 Our findings support the role of the GLS long microsatellite in the development of HE; this could be important for identifying susceptible patients and for the prevention of this condition.
25482439 GLS1 has a key role in coupling glutaminolysis of the TCA cycle with elevated glucose uptake and consequently the growth of prostate cancer cells
25297978 GABAergic neurons and astrocytes express Gls and Gls2 isoenzymes in nucleus and mitochondria, in addition to glutamatergic neurons
24755074 The rate of Glu decarboxylation into GABA by Glnase is an order of magnitude lower than that of Glutamate decarboxylase. Potential impact on the mechanistic aspects of Gln-Glu shuttle in neuroscience and glutaminolysis in tumors, is discussed.
24696726 These results suggest that the expression of GLS1 is upregulated and correlates with clinicopathological factors in colorectal cancer.
24333121 Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations.
24276018 Silencing GLS or overexpressing GLS2 induces growth inhibition in glioma cell lines.
24122876 our data indicate that ErbB2 activation promotes GLS1 expression via a PI3K-Akt-independent NF-kappaB pathway in breast cancer cells, identifying another oncogenic signaling pathway which stimulates GLS1 expression
24086752 STAT1 regulates human glutaminase 1 promoter activity
23935106 activated glutaminase C (GAC) self-assembles into a helical, fiber-like double-stranded oligomer and propose a molecular model consisting of seven tetramer copies per turn per strand interacting via the N-terminal domains
23722553 A glutaminase inhibitor reduced conversion of (13)C-pyruvate to alanine.
23636801 stromal expression of the glutamine-metabolism-related proteins GLS1, GDH, ASCT2 increases with worsening histological phyllodes tumor grade.
23578284 neuronal glutaminase is a potential component of neurotoxicity during inflammation and modulation of glutaminase may provide therapeutic avenues for neurodegenerative diseases.
23507704 HER2- type breast cancer had the highest expression of stromal GLS1, tumoral GDH, stromal GDH, and tumoral ASCT, while TNBC had the lowest tumoral GDH expression.
22892846 NSCLC cell lines depend on Gln for glutaminolysis to a varying degree, in which the GLS1 splice variant GAC plays an essential role and is a potential target for cancer metabolism-directed therapy.
22538822 KGA activity in cells is stimulated by EGF, and KGA associates with all three kinase components of the Raf-1/Mek2/Erk signaling module.
22479354 Data indicate that both HIV-1 infection and IFN-alpha treatment increase glutaminase 1 (GLS1) expression through STAT1 phosphorylation and by binding to the GLS1 promoter.
22360420 A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration.
22326218 Inhibition of Gls1 kills lung cancer cells that overexpress MYC and catabolize glutamine.
22106309 GLS1 differs from PFKFB3 in that its recognition by APC/C-Cdh1 during S phase requires the presence of both a Lys-Glu-Asn box (KEN box) and a destruction box (D box) rather than a KEN box alone.
22049910 first report of full-length crystal structure of a splice variant of GLS1 in presence/absence of BPTES, an allosteric inhibitor: 2 BPTES molecules bind at interface of GLS1 tetramer; appear to lock GLS1 tetramer into nonproductive conformation
21852960 Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia
21457947 This studt demonistrated that the genetic variation in the glutaminase gene GLS1 is related the glutamine/glutamate ratio in brain.
21234284 Glutaminase: a hot spot for regulation of cancer cell metabolism.
21045145 Data show that the ability to selectively slow growth in cells with IDH1 mutations by inhibiting glutaminase suggesting a unique reprogramming of intermediary metabolism and a potential therapeutic strategy.
20877624 Observational study of gene-disease association. (HuGE Navigator)
20820037 This study identifies mutations in the gene sequence for glutaminase that are associated with development of hepatic encephalopathy in patients with cirrhosis
20820037 Observational study of gene-disease association. (HuGE Navigator)
20659789 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
20438785 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20406964 Observational study of gene-disease association. (HuGE Navigator)
19500843 GA mRNA and protein expression was not different between normal and fetal growth restriction pregnancy
19428810 Multiple transcripts for glutaminase genes and simultaneous expression of glutaminase isoforms have been reported in mammalian tissues and cells--REVIEW
19428809 this brief review summarizes available data on the expression profiles and activities of glutaminase isoenzymes in different neoplastic tissues--REVIEW
19428808 Glutaminase is considered as the main glutamate-producer enzyme in brain--REVIEW
19423540 Observational study of gene-disease association. (HuGE Navigator)
19222703 Release of glutaminase from dysfunctional macrophages is a possible mechanism of glutaminase-mediated production of excitotoxic glutamate during the pathogenic process of human immunodeficiency virus (HIV)-1 associated dementia.
19219026 c-Myc transcriptionally represses miR-23a and miR-23b, resulting in greater expression of their target protein, mitochondrial glutaminase, in human P-493 B lymphoma cells and PC3 prostate cancer cells
19156168 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17669570 Observational study of gene-disease association. (HuGE Navigator)
15642443 Observational study of gene-disease association. (HuGE Navigator)
15496140 K glutaminase isoform is up-regulated with increased rates of proliferation in cancer cells, whereas prevalence of the L isoform seems to be related with resting or quiescent cell states
15246207 possible role for intestinal glutaminase in the pathogenesis of hepatic encephalopathy
14722097 human neutrophils appeared to utilize glutamine and posess the appropriate glutaminase enzyme for metabolizing glutamine.
12579526 Data suggest that glutaminase is an important factor in melanoma cell proliferation.

AA Sequence

MMRLRGSGMLRDLLLRSPAGVSATLRRAQPLVTLCRRPRGGGRPAAGPAAAARLHPWWGGGGWPAEPLAR      1 - 70
GLSSSPSEILQELGKGSTHPQPGVSPPAAPAAPGPKDGPGETDAFGNSEGKELVASGENKIKQGLLPSLE     71 - 140
DLLFYTIAEGQEKIPVHKFITALKSTGLRTSDPRLKECMDMLRLTLQTTSDGVMLDKDLFKKCVQSNIVL    141 - 210
LTQAFRRKFVIPDFMSFTSHIDELYESAKKQSGGKVADYIPQLAKFSPDLWGVSVCTVDGQRHSTGDTKV    211 - 280
PFCLQSCVKPLKYAIAVNDLGTEYVHRYVGKEPSGLRFNKLFLNEDDKPHNPMVNAGAIVVTSLIKQGVN    281 - 350
NAEKFDYVMQFLNKMAGNEYVGFSNATFQSERESGDRNFAIGYYLKEKKCFPEGTDMVGILDFYFQLCSI    351 - 420
EVTCESASVMAATLANGGFCPITGERVLSPEAVRNTLSLMHSCGMYDFSGQFAFHVGLPAKSGVAGGILL    421 - 490
VVPNVMGMMCWSPPLDKMGNSVKGIHFCHDLVSLCNFHNYDNLRHFAKKLDPRREGGDQRVKSVINLLFA    491 - 560
AYTGDVSALRRFALSAMDMEQRDYDSRTALHVAAAEGHVEVVKFLLEACKVNPFPKDRWNNTPMDEALHF    561 - 630
GHHDVFKILQEYQVQYTPQGDSDNGKENQTVHKNLDGLL                                   631 - 669
//

Text Mined References (76)

PMID Year Title
27089238 2016 The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy.
26710269 2015 MiRNA-192 [corrected] and miRNA-204 Directly Suppress lncRNA HOTTIP and Interrupt GLS1-Mediated Glutaminolysis in Hepatocellular Carcinoma.
26575584 2016 Inhibition of mitochondrial glutaminase activity reverses acquired erlotinib resistance in non-small cell lung cancer.
26134042 2015 Antitumor effects of a drug combination targeting glycolysis, glutaminolysis and de novo synthesis of fatty acids.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25915584 2015 Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis.
25880019 2015 A genetic variant in the promoter of phosphate-activated glutaminase is associated with hepatic encephalopathy.
25482439 2015 Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer.
25297978 2015 Expression of Gls and Gls2 glutaminase isoforms in astrocytes.
24755074 2014 Glutaminase catalyzes reaction of glutamate to GABA.
24696726 2014 Expression of glutaminase is upregulated in colorectal cancer and of clinical significance.
24333121 2014 Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations.
24276018 2014 Both GLS silencing and GLS2 overexpression synergize with oxidative stress against proliferation of glioma cells.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24122876 2014 ErbB2 activation upregulates glutaminase 1 expression which promotes breast cancer cell proliferation.
24086752 2013 STAT1 regulates human glutaminase 1 promoter activity through multiple binding sites in HIV-1 infected macrophages.
23935106 2013 Active glutaminase C self-assembles into a supratetrameric oligomer that can be disrupted by an allosteric inhibitor.
23722553 2013 Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors.
23636801 2013 The expression of glutamine-metabolism-related proteins in breast phyllodes tumors.
23578284 2013 IL-1? and TNF-? induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase.
23507704 2013 Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer.
22892846 2012 Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth.
22538822 2012 Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism.
22479354 2012 Interferon-? regulates glutaminase 1 promoter through STAT1 phosphorylation: relevance to HIV-1 associated neurocognitive disorders.
22360420 2012 Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.
22326218 2012 The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type.
22228304 2012 Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism.
22106309 2011 Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells.
22049910 2011 Full-length human glutaminase in complex with an allosteric inhibitor.
21852960 2011 Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia.
21757002 2011 The nuclear receptor FXR regulates hepatic transport and metabolism of glutamine and glutamate.
21457947 2011 Relationship between genetic variation in the glutaminase gene GLS1 and brain glutamine/glutamate ratio measured in vivo.
21269460 2011 Initial characterization of the human central proteome.
21234284 2010 Glutaminase: a hot spot for regulation of cancer cell metabolism?
21045145 2010 Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20820037 2010 Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study.
20659789 2010 Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data.
20438785 2010 Polymorphisms in innate immunity genes and risk of childhood leukemia.
20406964 2010 Risk of meningioma and common variation in genes related to innate immunity.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19500843 2009 Expression of enzymes regulating placental ammonia homeostasis in human fetal growth restricted pregnancies.
19428810 A novel glutaminase isoform in mammalian tissues.
19428809 Glutamine in neoplastic cells: focus on the expression and roles of glutaminases.
19428808 New insights into brain glutaminases: beyond their role on glutamatergic transmission.
19423540 2009 Common variation in genes related to innate immunity and risk of adult glioma.
19222703 2009 In vitro glutaminase regulation and mechanisms of glutamate generation in HIV-1-infected macrophage.
19219026 2009 c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism.
19156168 2009 Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
19139490 2009 A strategy for precise and large scale identification of core fucosylated glycoproteins.
17940881 2008 Relative expression of mRNAS coding for glutaminase isoforms in CNS tissues and CNS tumors.
17669570 2007 Increased plasma glutamate by antipsychotic medication and its relationship to glutaminase 1 and 2 genotypes in schizophrenia -- Juntendo University Schizophrenia Projects (JUSP).
16899818 2006 Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to neurite terminals and reduces glutamate levels.
15642443 2005 An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia.
15496140 2005 Co-expression of glutaminase K and L isoenzymes in human tumour cells.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15246207 2004 Intestinal glutaminase activity is increased in liver cirrhosis and correlates with minimal hepatic encephalopathy.
14759258 2004 An unappreciated role for RNA surveillance.
14722097 2004 Granule localization of glutaminase in human neutrophils and the consequence of glutamine utilization for neutrophil activity.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12579526 2003 Human cutaneous melanoma expresses a significant phosphate-dependent glutaminase activity: a comparison with the surrounding skin of the same patient.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11163757 2001 The C-terminus of human glutaminase L mediates association with PDZ domain-containing proteins.
11130979 2000 Identification of two human glutaminase loci and tissue-specific expression of the two related genes.
11059811 2000 Phosphate-activated glutaminase and mitochondrial glutamine transport in the brain.
11015561 1999 Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing.
10719215 2000 Isolation, characterization and expression of a human brain mitochondrial glutaminase cDNA.
10620514 2000 Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase.
10048485 1998 Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.
8896557 1996 Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats.
8499480 1993 Phosphate-dependent glutaminase of rat skeletal muscle. Some properties and possible role in glutamine metabolism.
6825316 1983 Glutaminase in human platelets.
6682827 1983 Genetic control of platelet glutaminase: a twin study.
3531404 1986 Phosphate-activated glutaminase in the crude mitochondrial fraction (P2 fraction) from human brain cortex.
2571577 1989 A glutaminase (gis) gene maps to mouse chromosome 1, rat chromosome 9, and human chromosome 2.
1680606 1991 Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization.