glutaminase | Glutaminases | IUPHAR/BPS Guide to PHARMACOLOGY

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Target not currently curated in GtoImmuPdb

Target id: 2891

Nomenclature: glutaminase

Family: Glutaminases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 669 2q32-q34 GLS glutaminase
Mouse - 674 1 C1.1 Gls glutaminase
Rat - 674 9q31-q32 Gls glutaminase
Gene and Protein Information Comments
The table above provides details of human isoform 1. hGLS isoform 2 is shorter (598aa) and has a distinct C-terminus, compared to isoform 1. We also show the longer isoforms of the rat and mouse Gls proteins.
Previous and Unofficial Names
GLS1 | glutaminase 1 | GAC | L-glutamine amidohydrolase | glutaminase kidney isoform | K-glutaminase | Gls
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
telaglenastat Hs Inhibition 8.3 pIC50 6
pIC50 8.3 (IC50 5x10-9 M) [6]
General Comments
Glutaminase is the first enzyme in the glutaminolysis pathway. GLS gene products are expressed in the kidney (where it is involved in maintaining acid-base balance), in the brain (where it is essential for synthesizing the brain neurotransmitter glutamate), in cardiac muscle, skeletal muscle and pancreas but is NOT expressed in the liver. Glutaminase C (GAC) and kidney-type glutaminase (KGA) are splice variants of the GLS gene, produced by tissue-specific alternative splicing of a single pre-mRNA [1,3].

Glutaminase activity is being targeted for pharmacological inhibition as a potential anti-cancer treatment [2,4-5], based in part on the discovery that the GAC isoform is the predominant isoform expressed by breast cancer cells which are highly dependent on glutaminolysis for growth and survival [1].


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1. Cassago A, Ferreira AP, Ferreira IM, Fornezari C, Gomes ER, Greene KS, Pereira HM, Garratt RC, Dias SM, Ambrosio AL. (2012) Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism. Proc. Natl. Acad. Sci. U.S.A., 109 (4): 1092-7. [PMID:22228304]

2. Chakrabarti G, Moore ZR, Luo X, Ilcheva M, Ali A, Padanad M, Zhou Y, Xie Y, Burma S, Scaglioni PP et al.. (2015) Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ß-lapachone. Cancer Metab, 3: 12. [PMID:26462257]

3. Elgadi KM, Meguid RA, Qian M, Souba WW, Abcouwer SF. (1999) Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing. Physiol. Genomics, 1 (2): 51-62. [PMID:11015561]

4. Gross MI, Demo SD, Dennison JB, Chen L, Chernov-Rogan T, Goyal B, Janes JR, Laidig GJ, Lewis ER, Li J et al.. (2014) Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol. Cancer Ther., 13 (4): 890-901. [PMID:24523301]

5. Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, Saland E, Decroocq J, Maciel TT, Lambert M et al.. (2015) Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood, 126 (11): 1346-56. [PMID:26186940]

6. Li J, Chen L, Goyal B, Laidig G, Stanton TF, Sjogren EB. (2013) Heterocyclic inhibitors of glutaminase. Patent number: US 8604016 B2. Assignee: Calithera Biosciences Inc.. Priority date: 21/11/2011. Publication date: 10/12/2013.

How to cite this page Glutaminases: glutaminase. Last modified on 02/03/2016. Accessed on 11/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY,