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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 669 | 2q32.2 | GLS | glutaminase | |
| Mouse | - | 674 | 1 26.86 cM | Gls | glutaminase | |
| Rat | - | 674 | 9q22 | 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 |
| K-glutaminase | GLS1 | glutaminase 1 | GAC | L-glutamine amidohydrolase | glutaminase kidney isoform | Gls |
| Database Links |
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| Alphafold | O94925 (Hs), D3Z7P3 (Mm), P13264 (Rn) |
| CATH/Gene3D | 1.25.40.20 |
| ChEMBL Target | CHEMBL2146302 (Hs), CHEMBL4523110 (Mm), CHEMBL4523186 (Rn) |
| Ensembl Gene | ENSG00000115419 (Hs), ENSMUSG00000026103 (Mm), ENSRNOG00000056246 (Rn) |
| Entrez Gene | 2744 (Hs), 14660 (Mm), 24398 (Rn) |
| Human Protein Atlas | ENSG00000115419 (Hs) |
| KEGG Gene | hsa:2744 (Hs), mmu:14660 (Mm), rno:24398 (Rn) |
| OMIM | 138280 (Hs) |
| Pharos | O94925 (Hs) |
| RefSeq Nucleotide | NM_014905 (Hs), NM_001256310 (Hs), NM_001113383 (Mm), NM_001081081 (Mm), NM_012569 (Rn), NM_001109968 (Rn) |
| RefSeq Protein | NP_055720 (Hs), NP_001243239 (Hs), NP_001106854 (Mm), NP_00107455 (Mm), NP_036701 (Rn), NP_001103438 (Rn) |
| UniProtKB | O94925 (Hs), D3Z7P3 (Mm), P13264 (Rn) |
| Wikipedia | GLS (Hs) |
Download all structure-activity data for this target as a CSV file 
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| General Comments |
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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]. |
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 USA, 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.
7. Soth MJ, Le K, Di Francesco ME, Hamilton MM, Liu G, Burke JP, Carroll CL, Kovacs JJ, Bardenhagen JP, Bristow CA et al.. (2020) Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties. J Med Chem, 63 (21): 12957-12977. [PMID:33118821]
3.5.1.2 Glutaminases: glutaminase. Last modified on 06/06/2023. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2891.
