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Details on Person UniProt:O94925-1 GLS
| Class:Id | ReferenceIsoform:402077 |
|---|---|
| _chainChangeLog | transit peptide:1-16 added on Fri February 6 2015;chain:17-669 added on Fri February 6 2015;transit peptide:1-16 for 402077 removed on Fri August 9 2019;chain:17-669 for 402077 removed on Fri August 9 2019;transit peptide:1-54 for 402077 added on Fri August 9 2019;chain:55-669 for 402077 added on Fri August 9 2019;chain:73-669 for 402077 added on Fri August 9 2019 |
| _displayName | UniProt:O94925-1 GLS |
| _timestamp | 2025-02-21 19:28:12 |
| chain | transit peptide:1-54 chain:55-669 chain:73-669 |
| checksum | 4E5E63505E84E0B7 |
| comment | 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).FUNCTION Lacks catalytic activity.CATALYTIC ACTIVITY L-glutamine + H2O = L-glutamate + NH4(+)ACTIVITY REGULATION Isoform 1 and isoform 3 are activated by phosphate. Inhibited by BPTES. BPTES binds between subunits and favors dissociation of the tetramer into dimers (PubMed:22049910). Inhibited by 6-diazo-5-oxo-L-norleucine (DON) (PubMed:24451979). Enzyme activity is stimulated by phosphorylation (PubMed:22538822).BIOPHYSICOCHEMICAL PROPERTIES Homotetramer, dimer of dimers (PubMed:22538822, PubMed:26988803, PubMed:28526749, PubMed:29317493). The tetramers can assemble into rod-like oligomers (in vitro), but the physiological significance of this is not clear (By similarity). Interacts with RAF1 and MAP2K2 (PubMed:22538822). Interacts with ATCAY; the interaction is direct and may control GLS localization, negatively regulating its activity.SUBCELLULAR LOCATION 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.SUBCELLULAR LOCATION Produced by the proteolytic processing of the 74-kDa cytosolic precursor.SUBCELLULAR LOCATION Produced by the proteolytic processing of the 74-kDa cytosolic precursor.ALTERNATIVE PRODUCTS 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.DOMAIN The C-terminal ANK repeats prevent the assembly of the supra-tetrameric filaments.DOMAIN A highly mobile activation loop at the dimer-dimer interface is important for enzyme activity.PTM 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the glutaminase family.CAUTION Isoform 3 is predicted to be expressed at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Contrary to expectations, it has been shown to be well expressed, and the encoded protein is detected in mitochondria (PubMed:11015561, PubMed:17940881, PubMed:22228304).SEQUENCE CAUTION Extended N-terminus. |
| created | [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 |
| description | recommendedName: Glutaminase kidney isoform, mitochondrial shortName: GLS ecNumber evidence="7 9 10 11 12 13"3.5.1.2 alternativeName: K-glutaminase alternativeName: L-glutamine amidohydrolase component recommendedName: fullName evidence="2"Glutaminase kidney isoform, mitochondrial 68 kDa chain /component component recommendedName: fullName evidence="2"Glutaminase kidney isoform, mitochondrial 65 kDa chain /component |
| geneName | GLS GLS1 KIAA0838 |
| identifier | O94925 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing ANK repeat Cataract Cytoplasm Direct protein sequencing Disease variant Epilepsy Hydrolase Mitochondrion Phosphoprotein Proteomics identification Reference proteome Repeat Transit peptide |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | GLS |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8996591] ENSEMBL:ENSG00000115419 GLS [Homo sapiens] |
| secondaryIdentifier | GLSK_HUMAN Q9UL05 Q9UL06 Q9UL07 Q9UN40 |
| sequenceLength | 669 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | O94925-1 |
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No pathways have been reviewed or authored by UniProt:O94925-1 GLS (402077)
