GLUL
entrez
2752
canonical
uniprot
P15104
canonical
ensembl
ENSG00000135821
resolver
ensp
ENSP00000307900
resolver
ensp
ENSP00000356537
resolver
ensp
ENSP00000398320
resolver
enst
ENST00000311223
resolver
enst
ENST00000331872
resolver
enst
ENST00000417584
resolver
genesymbol
GLUL
resolver
genesymbol
PIG59
resolver
genesymbol_syn
GLNS
resolver
genesymbol_syn
GLUL
resolver
hgnc
HGNC:4341
resolver
uniprot
A0A024R956
resolver
uniprot
A8YXX4
resolver
uniprot
Q499Y9
resolver
uniprot
Q5T9Z1
resolver
uniprot
Q7Z3W4
resolver
uniprot
Q8IZ17
resolver
uniprot_entry
A8YXX4_HUMAN
resolver
uniprot_entry
GLNA_HUMAN
resolver
uniprot_sec
A0A024R956
resolver
uniprot_sec
Q499Y9
resolver
uniprot_sec
Q5T9Z1
resolver
uniprot_sec
Q7Z3W4
resolver
uniprot_sec
Q8IZ17
resolver
activity_regulation
ACTIVITY REGULATION: Glutamine synthetase activity is inhibited by methionine sulfoximine (MSO) (PubMed:30158707). {ECO:0000269|PubMed:30158707}.
uniprot
proteins
amino_acid_sequence
MTTSASSHLNKGIKQVYMSLPQGEKVQAMYIWIDGTGEGLRCKTRTLDSEPKCVEELPEWNFDGSSTLQSEGSNSDMYLVPAAMFRDPFRKDPNKLVLCEVFKYNRRPAETNLRHTCKRIMDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADRAYGRDIVEAHYRACLYAGVKIAGTNAEVMPAQWEFQIGPCEGISMGDHLWVARFILHRVCEDFGVIATFDPKPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIEKLSKRHQYHIRAYDPKGGLDNARRLTGFHETSNINDFSAGVANRSASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRTCLLNETGDEPFQYKN
uniprot
proteins
disease_involvement
DISEASE: Glutamine deficiency, congenital (GLND) [MIM:610015]: An autosomal recessive disorder characterized by variable brain malformations, encephalopathy, severe developmental delay, seizures, and decreased glutamine levels in bodily fluids. Death in early infancy may occur. {ECO:0000269|PubMed:16267323, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:38579670}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 116 (DEE116) [MIM:620806]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE116 is autosomal dominant form characterized by severe developmental delay, seizures, and white matter abnormalities. {ECO:0000269|PubMed:38579670}. Note=The disease is caused by variants affecting the gene represented in this entry. DEE116 is caused by variants that disrupt the canonical translation start codon in GLUL resulting in initiation of translation at Met-18 (PubMed:38579670). The resulting protein is enzymatically competent but insensitive to negative feedback regulation via glutamine-induced degradation. {ECO:0000269|PubMed:38579670}.
uniprot
proteins
ec_number
2.3.1.225
uniprot
proteins
ec_number
6.3.1.2
uniprot
proteins
function
FUNCTION: Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:16267323, PubMed:30158707, PubMed:36289327). 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). Plays a key role in ammonium detoxification during erythropoiesis: the glutamine synthetase activity is required to remove ammonium generated by porphobilinogen deaminase (HMBS) during heme biosynthesis to prevent ammonium accumulation and oxidative stress (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). 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 (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351). 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 (PubMed:36289327). {ECO:0000250|UniProtKB:P15105, ECO:0000269|PubMed:16267323, ECO:0000269|PubMed:18662667, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:30158707, ECO:0000269|PubMed:36289327}.
uniprot
proteins
mass_dalton
42064
uniprot
proteins
mutagenesis
MUTAGEN 2..17; /note="Missing: Is stable in high glutamine conditions and does not undergo glutamine-induced degradation."; /evidence="ECO:0000269|PubMed:38579670"; MUTAGEN 11; /note="K->A: Increased ubiquitination and increased proteasomal degradation; when associated with A-14."; /evidence="ECO:0000269|PubMed:26990986"; MUTAGEN 11; /note="K->R: Decreased glutamine-induced acetylation; when associated with R-14. Decreased ubiquitination and decreased proteasomal degradation; when associated with R-14."; /evidence="ECO:0000269|PubMed:26990986"; MUTAGEN 14; /note="K->A: Increased ubiquitination and increased proteasomal degradation; when associated with A-11."; /evidence="ECO:0000269|PubMed:26990986"; MUTAGEN 14; /note="K->R: Decreased glutamine-induced acetylation; when associated with R-11. Decreased ubiquitination and decreased proteasomal degradation; when associated with R-11."; /evidence="ECO:0000269|PubMed:26990986"; MUTAGEN 209; /note="C->A: Reduced ability to mediate autopalmitoylation."; /evidence="ECO:0000269|PubMed:30158707"; MUTAGEN 299; /note="R->E: Loss of glutamine synthase activity. Does not affect interaction with BEST2."; /evidence="ECO:0000269|PubMed:36289327"; MUTAGEN 324; /note="R->A: Decreases ribosomal 40S subunit synthesis. Loss of nucleolar location of BYSL."; /evidence="ECO:0000269|PubMed:26711351
uniprot
proteins
post_translational_modification
PTM: Acetylated by EP300/p300; acetylation is stimulated by increased glutamine levels and promotes ubiquitin-mediated proteasomal degradation. {ECO:0000269|PubMed:26990986}.; PTM: Palmitoylated; undergoes autopalmitoylation. {ECO:0000305|PubMed:30158707}.; PTM: 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 (PubMed:26990986). {ECO:0000250|UniProtKB:P15105, ECO:0000269|PubMed:26990986}.
uniprot
proteins
protein_family
Glutamine synthetase family
uniprot
proteins
pubmed
12387715
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16267323
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
1681907
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18005987
uniprot
proteins
pubmed
18555765
uniprot
proteins
pubmed
18662667
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26711351
uniprot
proteins
pubmed
26990986
uniprot
proteins
pubmed
2888076
uniprot
proteins
pubmed
30158707
uniprot
proteins
pubmed
36289327
uniprot
proteins
pubmed
38579670
uniprot
proteins
pubmed
7909780
uniprot
proteins
sequence_length
373
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:30158707, ECO:0000269|PubMed:36289327}. Microsome {ECO:0000250|UniProtKB:P09606}. Mitochondrion {ECO:0000250|UniProtKB:P09606}. Cell membrane {ECO:0000269|PubMed:30158707}; Lipid-anchor {ECO:0000269|PubMed:30158707}. Note=Mainly localizes in the cytosol, with a fraction associated with the cell membrane. {ECO:0000269|PubMed:30158707}.
uniprot
proteins