Q9QY94 · GLNA_ACOCA
- ProteinGlutamine synthetase
- GeneGLUL
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids373 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (By similarity).
Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity).
Essential for proliferation of fetal skin fibroblasts. Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation. May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (By similarity).
Through the interaction with BEST2, inhibits BEST2 channel activity by affecting the gating at the aperture in the absence of intracellular L-glutamate, but sensitizes BEST2 to intracellular L-glutamate, which promotes the opening of BEST2 and thus relieves its inhibitory effect on BEST2 (By similarity).
Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity).
Essential for proliferation of fetal skin fibroblasts. Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation. May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (By similarity).
Through the interaction with BEST2, inhibits BEST2 channel activity by affecting the gating at the aperture in the absence of intracellular L-glutamate, but sensitizes BEST2 to intracellular L-glutamate, which promotes the opening of BEST2 and thus relieves its inhibitory effect on BEST2 (By similarity).
Catalytic activity
- ATP + L-glutamate + NH4+ = ADP + H+ + L-glutamine + phosphate
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Activity regulation
Glutamine synthetase activity is inhibited by methionine sulfoximine (MSO).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 134 | ATP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 134 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 136 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 196 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 203 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 203-208 | ATP (UniProtKB | ChEBI) | ||||
Sequence: EFQIGP | ||||||
Binding site | 246-247 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: NW | ||||||
Binding site | 253 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 255-257 | ATP (UniProtKB | ChEBI) | ||||
Sequence: NFS | ||||||
Binding site | 319 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 319 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 324 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 336-338 | ADP (UniProtKB | ChEBI) | ||||
Sequence: YFE | ||||||
Binding site | 338 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 340 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | mitochondrion | |
Cellular Component | plasma membrane | |
Molecular Function | ATP binding | |
Molecular Function | glutamine synthetase activity | |
Molecular Function | metal ion binding | |
Molecular Function | protein-cysteine S-palmitoyltransferase activity | |
Biological Process | angiogenesis | |
Biological Process | glutamine biosynthetic process | |
Biological Process | protein palmitoylation | |
Biological Process | regulation of endothelial cell migration | |
Biological Process | regulation of sprouting angiogenesis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGlutamine synthetase
- EC number
- Short namesGS
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Deomyinae > Acomys
Accessions
- Primary accessionQ9QY94
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Lipid-anchor
Note: Mainly localizes in the cytosol, with a fraction associated with the cell membrane.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000153135 | 2-373 | Glutamine synthetase | |||
Sequence: ATSASSHLNKGIKQMYMSLPQGEKVQAMYIWVDGTGEGLRCKTRTLDCEPKCVEELPEWNFDGSSTFQSEGSNSDMYLSPVAMFRDPFRKEPNKLVFCEVFKYNRKPAETNLRHSCKRIMDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADKAYGRDIVEAHYRACLYAGVKITGTNAEVMPAQWEFQIGPCEGIRMGDHLWVARFILHRVCEDFGVIATFDPKPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIDKLSKRHQYHIRAYDPKGGLDNARRLTGFHETSNINDFSAGVANRGASIRIPRTVGQEKRGYFEDRRPSANCDPYAVTEAIVRTCLLNETGNEPFQYKN | ||||||
Modified residue | 11 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 14 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 104 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 343 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Palmitoylated; undergoes autopalmitoylation.
Acetylated by EP300/p300; acetylation is stimulated by increased glutamine levels and promotes ubiquitin-mediated proteasomal degradation.
Ubiquitinated by ZNRF1 (By similarity).
Ubiquitinated by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(CRBN), leading to proteasomal degradation (By similarity).
Ubiquitinated by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(CRBN), leading to proteasomal degradation (By similarity).
Keywords
- PTM
Interaction
Subunit
Decamer; composed of two pentamers (By similarity).
Interacts with PALMD (By similarity).
Interacts with RHOJ (By similarity).
Interacts with BEST2; this interaction tethers a fraction of GLUL to the membrane, causing a decrease of cytosolic glutamine synthase (GS) activity and inhibits the chloride channel activity of BEST2 by affecting the gating at the aperture in the absence of intracellular glutamate (By similarity).
Interacts with PALMD (By similarity).
Interacts with RHOJ (By similarity).
Interacts with BEST2; this interaction tethers a fraction of GLUL to the membrane, causing a decrease of cytosolic glutamine synthase (GS) activity and inhibits the chloride channel activity of BEST2 by affecting the gating at the aperture in the absence of intracellular glutamate (By similarity).
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-25 | Required for glutamine-induced ubiquitination by CRL4(CRBN) and proteasomal degradation | ||||
Sequence: ATSASSHLNKGIKQMYMSLPQGEK | ||||||
Domain | 24-106 | GS beta-grasp | ||||
Sequence: EKVQAMYIWVDGTGEGLRCKTRTLDCEPKCVEELPEWNFDGSSTFQSEGSNSDMYLSPVAMFRDPFRKEPNKLVFCEVFKYNR | ||||||
Domain | 113-373 | GS catalytic | ||||
Sequence: LRHSCKRIMDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADKAYGRDIVEAHYRACLYAGVKITGTNAEVMPAQWEFQIGPCEGIRMGDHLWVARFILHRVCEDFGVIATFDPKPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIDKLSKRHQYHIRAYDPKGGLDNARRLTGFHETSNINDFSAGVANRGASIRIPRTVGQEKRGYFEDRRPSANCDPYAVTEAIVRTCLLNETGNEPFQYKN |
Sequence similarities
Belongs to the glutamine synthetase family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length373
- Mass (Da)42,165
- Last updated2007-01-23 v3
- Checksum51BAD0B2EBA18AB6