GLNA_HUMAN
ID GLNA_HUMAN Reviewed; 373 AA.
AC P15104; Q499Y9; Q5T9Z1; Q7Z3W4; Q8IZ17;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Glutamine synthetase {ECO:0000303|PubMed:2888076, ECO:0000303|PubMed:30158707};
DE Short=GS {ECO:0000303|PubMed:1681907, ECO:0000303|PubMed:30158707};
DE EC=6.3.1.2 {ECO:0000269|PubMed:30158707};
DE AltName: Full=Glutamate--ammonia ligase {ECO:0000305};
DE AltName: Full=Palmitoyltransferase GLUL {ECO:0000305};
DE EC=2.3.1.225 {ECO:0000305|PubMed:30158707};
GN Name=GLUL {ECO:0000303|PubMed:30158707, ECO:0000312|HGNC:HGNC:4341};
GN Synonyms=GLNS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2888076; DOI=10.1093/nar/15.15.6293;
RA Gibbs C.S., Campbell K.E., Wilson R.H.;
RT "Sequence of a human glutamine synthetase cDNA.";
RL Nucleic Acids Res. 15:6293-6293(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1681907; DOI=10.1016/0167-4781(91)90111-x;
RA van den Hoff M.J.B., Geerts W.J.C., Das A.T., Moorman A.F.M., Lamers W.H.;
RT "cDNA sequence of the long mRNA for human glutamine synthase.";
RL Biochim. Biophys. Acta 1090:249-251(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=7909780; DOI=10.1016/0016-5085(94)90024-8;
RA Christa L., Simon M.T., Flinois J.P., Gebhardt R., Brechot C., Lasserre C.;
RT "Overexpression of glutamine synthetase in human primary liver cancer.";
RL Gastroenterology 106:1312-1320(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RA Haberle J., Koch H.G.;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Colon, Eye, Muscle, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain;
RX PubMed=12387715; DOI=10.1023/a:1020574003027;
RA Boksha I.S., Schonfeld H.J., Langen H., Muller F., Tereshkina E.B.,
RA Burbaeva G.S.H.;
RT "Glutamine synthetase isolated from human brain: octameric structure and
RT homology of partial primary structure with human liver glutamine
RT synthetase.";
RL Biochemistry (Mosc.) 67:1012-1020(2002).
RN [9]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18662667; DOI=10.1016/j.abb.2008.07.009;
RA Vermeulen T., Goerg B., Vogl T., Wolf M., Varga G., Toutain A., Paul R.,
RA Schliess F., Haeussinger D., Haeberle J.;
RT "Glutamine synthetase is essential for proliferation of fetal skin
RT fibroblasts.";
RL Arch. Biochem. Biophys. 478:96-102(2008).
RN [10]
RP INDUCTION.
RX PubMed=18555765; DOI=10.1016/j.bone.2008.04.016;
RA Olkku A., Mahonen A.;
RT "Wnt and steroid pathways control glutamate signalling by regulating
RT glutamine synthetase activity in osteoblastic cells.";
RL Bone 43:483-493(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF ARG-324.
RX PubMed=26711351; DOI=10.1016/j.celrep.2015.11.061;
RA Badertscher L., Wild T., Montellese C., Alexander L.T., Bammert L.,
RA Sarazova M., Stebler M., Csucs G., Mayer T.U., Zamboni N., Zemp I.,
RA Horvath P., Kutay U.;
RT "Genome-wide RNAi Screening Identifies Protein Modules Required for 40S
RT Subunit Synthesis in Human Cells.";
RL Cell Rep. 13:2879-2891(2015).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH RHOJ,
RP SUBCELLULAR LOCATION, PALMITOYLATION, TISSUE SPECIFICITY, AND MUTAGENESIS
RP OF CYS-209.
RX PubMed=30158707; DOI=10.1038/s41586-018-0466-7;
RA Eelen G., Dubois C., Cantelmo A.R., Goveia J., Bruening U., DeRan M.,
RA Jarugumilli G., van Rijssel J., Saladino G., Comitani F., Zecchin A.,
RA Rocha S., Chen R., Huang H., Vandekeere S., Kalucka J., Lange C.,
RA Morales-Rodriguez F., Cruys B., Treps L., Ramer L., Vinckier S.,
RA Brepoels K., Wyns S., Souffreau J., Schoonjans L., Lamers W.H., Wu Y.,
RA Haustraete J., Hofkens J., Liekens S., Cubbon R., Ghesquiere B.,
RA Dewerchin M., Gervasio F.L., Li X., van Buul J.D., Wu X., Carmeliet P.;
RT "Role of glutamine synthetase in angiogenesis beyond glutamine synthesis.";
RL Nature 561:63-69(2018).
RN [17] {ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 5-365 IN COMPLEX WITH ADP AND
RP MANGANESE, AND SUBUNIT.
RX PubMed=18005987; DOI=10.1016/j.jmb.2007.10.029;
RA Krajewski W.W., Collins R., Holmberg-Schiavone L., Jones T.A., Karlberg T.,
RA Mowbray S.L.;
RT "Crystal structures of mammalian glutamine synthetases illustrate
RT substrate-induced conformational changes and provide opportunities for drug
RT and herbicide design.";
RL J. Mol. Biol. 375:217-228(2008).
RN [18]
RP VARIANTS CSGD CYS-324 AND CYS-341, CHARACTERIZATION OF VARIANTS CSGD
RP CYS-324 AND CYS-341, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16267323; DOI=10.1056/nejmoa050456;
RA Haeberle J., Goerg B., Rutsch F., Schmidt E., Toutain A., Benoist J.-F.,
RA Gelot A., Suc A.-L., Hoehne W., Schliess F., Haeussinger D., Koch H.G.;
RT "Congenital glutamine deficiency with glutamine synthetase mutations.";
RL N. Engl. J. Med. 353:1926-1933(2005).
CC -!- FUNCTION: Glutamine synthetase that catalyzes the ATP-dependent
CC conversion of glutamate and ammonia to glutamine (PubMed:30158707,
CC PubMed:16267323). Its role depends on tissue localization: in the
CC brain, it regulates the levels of toxic ammonia and converts neurotoxic
CC glutamate to harmless glutamine, whereas in the liver, it is one of the
CC enzymes responsible for the removal of ammonia (By similarity).
CC Essential for proliferation of fetal skin fibroblasts
CC (PubMed:18662667). Independently of its glutamine synthetase activity,
CC required for endothelial cell migration during vascular development:
CC acts by regulating membrane localization and activation of the GTPase
CC RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May
CC act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and
CC then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a
CC role in ribosomal 40S subunit biogenesis (PubMed:26711351).
CC {ECO:0000250|UniProtKB:P15105, ECO:0000269|PubMed:16267323,
CC ECO:0000269|PubMed:18662667, ECO:0000269|PubMed:26711351,
CC ECO:0000269|PubMed:30158707}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-glutamate + NH4(+) = ADP + H(+) + L-glutamine +
CC phosphate; Xref=Rhea:RHEA:16169, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.1.2;
CC Evidence={ECO:0000269|PubMed:16267323, ECO:0000269|PubMed:30158707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + L-cysteinyl-[protein] = CoA + S-
CC hexadecanoyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:36683, Rhea:RHEA-
CC COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:74151;
CC EC=2.3.1.225; Evidence={ECO:0000305|PubMed:30158707};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P09606};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:18005987};
CC -!- ACTIVITY REGULATION: Glutamine synthetase activity is inhibited by
CC methionine sulfoximine (MSO). {ECO:0000269|PubMed:30158707}.
CC -!- SUBUNIT: Decamer; composed of two pentamers (PubMed:18005987).
CC Interacts with PALMD (By similarity). Interacts with RHOJ
CC (PubMed:30158707). {ECO:0000250|UniProtKB:P15105,
CC ECO:0000269|PubMed:18005987, ECO:0000269|PubMed:30158707}.
CC -!- INTERACTION:
CC P15104; P15104: GLUL; NbExp=6; IntAct=EBI-746653, EBI-746653;
CC P15104; Q9H4E5: RHOJ; NbExp=2; IntAct=EBI-746653, EBI-6285694;
CC P15104; Q9H4E5-1: RHOJ; NbExp=2; IntAct=EBI-746653, EBI-20738368;
CC P15104; P17735: TAT; NbExp=3; IntAct=EBI-746653, EBI-12046643;
CC P15104; B4URF7: PB2; Xeno; NbExp=2; IntAct=EBI-746653, EBI-6050648;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:30158707}.
CC Microsome {ECO:0000250|UniProtKB:P09606}. Mitochondrion
CC {ECO:0000250|UniProtKB:P09606}. Cell membrane
CC {ECO:0000269|PubMed:30158707}; Lipid-anchor
CC {ECO:0000269|PubMed:30158707}. Note=Mainly localizes in the cytosol,
CC with a fraction associated with the cell membrane.
CC {ECO:0000269|PubMed:30158707}.
CC -!- TISSUE SPECIFICITY: Expressed in endothelial cells.
CC {ECO:0000269|PubMed:30158707}.
CC -!- DEVELOPMENTAL STAGE: Expressed during early fetal stages.
CC {ECO:0000269|PubMed:18662667}.
CC -!- INDUCTION: By glucocorticoids. Vitamin D and the Wnt signaling pathway
CC inhibit its expression and activity. {ECO:0000269|PubMed:18555765}.
CC -!- PTM: Palmitoylated; undergoes autopalmitoylation.
CC {ECO:0000305|PubMed:30158707}.
CC -!- PTM: Ubiquitinated by ZNRF1. {ECO:0000250|UniProtKB:P15105}.
CC -!- DISEASE: Congenital systemic glutamine deficiency (CSGD) [MIM:610015]:
CC Rare developmental disorder with severe brain malformation resulting in
CC multi-organ failure and neonatal death. Glutamine is largely absent
CC from affected patients serum, urine and cerebrospinal fluid.
CC {ECO:0000269|PubMed:16267323}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glutamine synthetase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glutamine synthetase entry;
CC URL="https://en.wikipedia.org/wiki/Glutamine_synthetase";
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DR EMBL; Y00387; CAA68457.1; -; mRNA.
DR EMBL; X59834; CAA42495.1; -; mRNA.
DR EMBL; S70290; AAB30693.1; -; mRNA.
DR EMBL; AY486122; AAS57904.1; -; mRNA.
DR EMBL; AY486123; AAS57905.1; -; Genomic_DNA.
DR EMBL; BX537384; CAD97626.1; -; mRNA.
DR EMBL; AL139344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010037; AAH10037.1; -; mRNA.
DR EMBL; BC011700; AAH11700.1; -; mRNA.
DR EMBL; BC011852; AAH11852.1; -; mRNA.
DR EMBL; BC018992; AAH18992.1; -; mRNA.
DR EMBL; BC031964; AAH31964.1; -; mRNA.
DR EMBL; BC051726; AAH51726.1; -; mRNA.
DR CCDS; CCDS1344.1; -.
DR PIR; S18455; AJHUQ.
DR RefSeq; NP_001028216.1; NM_001033044.3.
DR RefSeq; NP_001028228.1; NM_001033056.3.
DR RefSeq; NP_002056.2; NM_002065.6.
DR RefSeq; XP_006711341.1; XM_006711278.1.
DR PDB; 2OJW; X-ray; 2.05 A; A/B/C/D/E=5-365.
DR PDB; 2QC8; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J=5-365.
DR PDB; 7EVT; X-ray; 2.95 A; A/B/C/D/E/F/G/H/I/J=23-373.
DR PDBsum; 2OJW; -.
DR PDBsum; 2QC8; -.
DR PDBsum; 7EVT; -.
DR AlphaFoldDB; P15104; -.
DR SMR; P15104; -.
DR BioGRID; 109014; 126.
DR DIP; DIP-308N; -.
DR IntAct; P15104; 39.
DR MINT; P15104; -.
DR STRING; 9606.ENSP00000307900; -.
DR BindingDB; P15104; -.
DR ChEMBL; CHEMBL4612; -.
DR DrugBank; DB11118; Ammonia.
DR DrugBank; DB06774; Capsaicin.
DR DrugBank; DB01212; Ceftriaxone.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB08794; Ethyl biscoumacetate.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB00130; L-Glutamine.
DR DrugBank; DB00134; Methionine.
DR DrugBank; DB00082; Pegvisomant.
DR DrugBank; DB00466; Picrotoxin.
DR DrugCentral; P15104; -.
DR iPTMnet; P15104; -.
DR PhosphoSitePlus; P15104; -.
DR BioMuta; GLUL; -.
DR REPRODUCTION-2DPAGE; IPI00010130; -.
DR UCD-2DPAGE; P15104; -.
DR EPD; P15104; -.
DR jPOST; P15104; -.
DR MassIVE; P15104; -.
DR MaxQB; P15104; -.
DR PaxDb; P15104; -.
DR PeptideAtlas; P15104; -.
DR PRIDE; P15104; -.
DR ProteomicsDB; 53107; -.
DR Antibodypedia; 1536; 686 antibodies from 42 providers.
DR DNASU; 2752; -.
DR Ensembl; ENST00000311223.9; ENSP00000307900.5; ENSG00000135821.19.
DR Ensembl; ENST00000331872.11; ENSP00000356537.6; ENSG00000135821.19.
DR Ensembl; ENST00000339526.8; ENSP00000344958.4; ENSG00000135821.19.
DR Ensembl; ENST00000417584.6; ENSP00000398320.2; ENSG00000135821.19.
DR GeneID; 2752; -.
DR KEGG; hsa:2752; -.
DR MANE-Select; ENST00000331872.11; ENSP00000356537.6; NM_001033044.4; NP_001028216.1.
DR UCSC; uc001gpa.3; human.
DR CTD; 2752; -.
DR DisGeNET; 2752; -.
DR GeneCards; GLUL; -.
DR HGNC; HGNC:4341; GLUL.
DR HPA; ENSG00000135821; Tissue enhanced (skeletal).
DR MalaCards; GLUL; -.
DR MIM; 138290; gene.
DR MIM; 610015; phenotype.
DR neXtProt; NX_P15104; -.
DR OpenTargets; ENSG00000135821; -.
DR Orphanet; 71278; Congenital brain dysgenesis due to glutamine synthetase deficiency.
DR PharmGKB; PA28743; -.
DR VEuPathDB; HostDB:ENSG00000135821; -.
DR eggNOG; KOG0683; Eukaryota.
DR GeneTree; ENSGT00390000010047; -.
DR HOGENOM; CLU_036762_1_1_1; -.
DR InParanoid; P15104; -.
DR OMA; DRRPNAN; -.
DR OrthoDB; 784869at2759; -.
DR PhylomeDB; P15104; -.
DR TreeFam; TF300491; -.
DR BioCyc; MetaCyc:HS06066-MON; -.
DR BRENDA; 6.3.1.2; 2681.
DR PathwayCommons; P15104; -.
DR Reactome; R-HSA-210455; Astrocytic Glutamate-Glutamine Uptake And Metabolism.
DR Reactome; R-HSA-8964539; Glutamate and glutamine metabolism.
DR SABIO-RK; P15104; -.
DR SignaLink; P15104; -.
DR SIGNOR; P15104; -.
DR BioGRID-ORCS; 2752; 36 hits in 1081 CRISPR screens.
DR ChiTaRS; GLUL; human.
DR EvolutionaryTrace; P15104; -.
DR GenomeRNAi; 2752; -.
DR Pharos; P15104; Tchem.
DR PRO; PR:P15104; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P15104; protein.
DR Bgee; ENSG00000135821; Expressed in endothelial cell and 204 other tissues.
DR ExpressionAtlas; P15104; baseline and differential.
DR Genevisible; P15104; HS.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045503; F:dynein light chain binding; IEA:Ensembl.
DR GO; GO:0016595; F:glutamate binding; IEA:Ensembl.
DR GO; GO:0004356; F:glutamate-ammonia ligase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR GO; GO:0030145; F:manganese ion binding; IEA:Ensembl.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019676; P:ammonia assimilation cycle; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; IDA:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0006538; P:glutamate catabolic process; TAS:BHF-UCL.
DR GO; GO:0006542; P:glutamine biosynthetic process; IBA:GO_Central.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0018345; P:protein palmitoylation; IDA:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; IDA:UniProtKB.
DR GO; GO:1904749; P:regulation of protein localization to nucleolus; IMP:UniProtKB.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; IDA:UniProtKB.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0042254; P:ribosome biogenesis; IMP:UniProtKB.
DR Gene3D; 3.10.20.70; -; 1.
DR InterPro; IPR008147; Gln_synt_b-grasp.
DR InterPro; IPR036651; Gln_synt_N.
DR InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR InterPro; IPR008146; Gln_synth_cat_dom.
DR InterPro; IPR027303; Gln_synth_gly_rich_site.
DR InterPro; IPR027302; Gln_synth_N_conserv_site.
DR Pfam; PF00120; Gln-synt_C; 1.
DR Pfam; PF03951; Gln-synt_N; 1.
DR SMART; SM01230; Gln-synt_C; 1.
DR SUPFAM; SSF54368; SSF54368; 1.
DR SUPFAM; SSF55931; SSF55931; 1.
DR PROSITE; PS00180; GLNA_1; 1.
DR PROSITE; PS00181; GLNA_ATP; 1.
DR PROSITE; PS51986; GS_BETA_GRASP; 1.
DR PROSITE; PS51987; GS_CATALYTIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Angiogenesis; ATP-binding; Cell membrane;
KW Cytoplasm; Disease variant; Endoplasmic reticulum; Ligase; Lipoprotein;
KW Magnesium; Manganese; Membrane; Metal-binding; Microsome; Mitochondrion;
KW Nucleotide-binding; Palmitate; Phosphoprotein; Reference proteome;
KW Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..373
FT /note="Glutamine synthetase"
FT /id="PRO_0000153139"
FT DOMAIN 24..106
FT /note="GS beta-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01330"
FT DOMAIN 113..373
FT /note="GS catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01331"
FT BINDING 134
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT BINDING 134
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:2QC8"
FT BINDING 136
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:2QC8"
FT BINDING 196
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:2QC8"
FT BINDING 203..208
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT BINDING 203
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:2QC8"
FT BINDING 246..247
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P9WN39"
FT BINDING 253
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:2QC8"
FT BINDING 255..257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT BINDING 319
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT BINDING 319
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P9WN39"
FT BINDING 324
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT BINDING 336..338
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT BINDING 338
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:2QC8"
FT BINDING 340
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P9WN39"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 104
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15105"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VARIANT 324
FT /note="R -> C (in CSGD; reduced glutamine synthetase
FT activity; dbSNP:rs80358214)"
FT /evidence="ECO:0000269|PubMed:16267323"
FT /id="VAR_026560"
FT VARIANT 341
FT /note="R -> C (in CSGD; suggests reduced glutamine
FT synthetase activity; dbSNP:rs80358215)"
FT /evidence="ECO:0000269|PubMed:16267323"
FT /id="VAR_026561"
FT MUTAGEN 209
FT /note="C->A: Reduced ability to mediate
FT autopalmitoylation."
FT /evidence="ECO:0000269|PubMed:30158707"
FT MUTAGEN 324
FT /note="R->A,C: Decreases ribolosomal 40S subunit synthesis.
FT Loss of nucleolar location of BYSL."
FT /evidence="ECO:0000269|PubMed:26711351"
FT CONFLICT 7
FT /note="S -> Y (in Ref. 7; AAH31964)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="F -> L (in Ref. 5; CAD97626)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="P -> T (in Ref. 7; AAH31964)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="A -> G (in Ref. 1; CAA68457)"
FT /evidence="ECO:0000305"
FT CONFLICT 322..323
FT /note="SI -> RL (in Ref. 2; CAA42495)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="D -> E (in Ref. 2; CAA42495)"
FT /evidence="ECO:0000305"
FT HELIX 5..8
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 11..18
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 40..49
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:2OJW"
FT TURN 64..68
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:2QC8"
FT STRAND 76..86
FT /evidence="ECO:0007829|PDB:2OJW"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:2QC8"
FT HELIX 114..123
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 124..127
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 130..140
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:2QC8"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:2OJW"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 173..186
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 213..232
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:7EVT"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 251..257
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:2OJW"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 267..278
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 281..287
FT /evidence="ECO:0007829|PDB:2OJW"
FT TURN 290..295
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:7EVT"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 321..325
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 327..332
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:2OJW"
FT HELIX 348..359
FT /evidence="ECO:0007829|PDB:2OJW"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:7EVT"
SQ SEQUENCE 373 AA; 42064 MW; 45390C100924FAF3 CRC64;
MTTSASSHLN KGIKQVYMSL PQGEKVQAMY IWIDGTGEGL RCKTRTLDSE PKCVEELPEW
NFDGSSTLQS EGSNSDMYLV PAAMFRDPFR KDPNKLVLCE VFKYNRRPAE TNLRHTCKRI
MDMVSNQHPW FGMEQEYTLM GTDGHPFGWP SNGFPGPQGP YYCGVGADRA YGRDIVEAHY
RACLYAGVKI AGTNAEVMPA QWEFQIGPCE GISMGDHLWV ARFILHRVCE DFGVIATFDP
KPIPGNWNGA GCHTNFSTKA MREENGLKYI EEAIEKLSKR HQYHIRAYDP KGGLDNARRL
TGFHETSNIN DFSAGVANRS ASIRIPRTVG QEKKGYFEDR RPSANCDPFS VTEALIRTCL
LNETGDEPFQ YKN
