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Database: UniProt
Entry: P15104
LinkDB: P15104
Original site: P15104 
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   07-APR-2021, entry version 220.
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   PDBsum; 2OJW; -.
DR   PDBsum; 2QC8; -.
DR   SMR; P15104; -.
DR   BioGRID; 109014; 59.
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; 642 antibodies.
DR   DNASU; 2752; -.
DR   Ensembl; ENST00000311223; ENSP00000307900; ENSG00000135821.
DR   Ensembl; ENST00000331872; ENSP00000356537; ENSG00000135821.
DR   Ensembl; ENST00000339526; ENSP00000344958; ENSG00000135821.
DR   Ensembl; ENST00000417584; ENSP00000398320; ENSG00000135821.
DR   GeneID; 2752; -.
DR   KEGG; hsa:2752; -.
DR   UCSC; uc001gpa.3; human.
DR   CTD; 2752; -.
DR   DisGeNET; 2752; -.
DR   GeneCards; GLUL; -.
DR   HGNC; HGNC:4341; GLUL.
DR   HPA; ENSG00000135821; Low tissue specificity.
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:ENSG00000135821.16; -.
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-MONOMER; -.
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   BioGRID-ORCS; 2752; 30 hits in 996 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 medial globus pallidus and 255 other tissues.
DR   ExpressionAtlas; P15104; baseline and differential.
DR   Genevisible; P15104; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004356; F:glutamate-ammonia ligase activity; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0008283; P:cell population proliferation; IDA:UniProtKB.
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:0009064; P:glutamine family amino acid metabolic process; TAS:Reactome.
DR   GO; GO:0001504; P:neurotransmitter uptake; TAS:Reactome.
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: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.
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   NP_BIND         203..208
FT                   /note="ATP"
FT                   /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT   NP_BIND         255..257
FT                   /note="ATP"
FT                   /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT   NP_BIND         336..338
FT                   /note="ADP"
FT                   /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT   REGION          246..247
FT                   /note="L-glutamate binding"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN39"
FT   METAL           134
FT                   /note="Manganese 1"
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   METAL           136
FT                   /note="Manganese 2"
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   METAL           196
FT                   /note="Manganese 2"
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   METAL           203
FT                   /note="Manganese 2"
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   METAL           253
FT                   /note="Manganese 1; via pros nitrogen"
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   METAL           338
FT                   /note="Manganese 1"
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   BINDING         134
FT                   /note="ATP"
FT                   /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT   BINDING         319
FT                   /note="ATP"
FT                   /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT   BINDING         319
FT                   /note="L-glutamate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN39"
FT   BINDING         324
FT                   /note="ATP"
FT                   /evidence="ECO:0007744|PDB:2OJW, ECO:0007744|PDB:2QC8"
FT   BINDING         340
FT                   /note="L-glutamate"
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:0007744|PDB:2OJW"
FT   HELIX           11..18
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          26..33
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          40..49
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           54..56
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          60..63
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   TURN            64..68
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          69..71
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           72..74
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   STRAND          76..86
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   TURN            88..90
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          95..102
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          106..108
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   HELIX           114..123
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           124..127
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          130..140
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          144..146
FT                   /evidence="ECO:0007744|PDB:2QC8"
FT   STRAND          158..160
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   TURN            167..169
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           173..186
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          190..195
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          201..210
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           213..232
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          235..237
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          245..247
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          251..257
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           259..262
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   TURN            264..266
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           267..278
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           281..287
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   TURN            290..295
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           296..298
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          314..316
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          321..325
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           327..332
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   STRAND          337..339
FT                   /evidence="ECO:0007744|PDB:2OJW"
FT   HELIX           348..359
FT                   /evidence="ECO:0007744|PDB:2OJW"
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
//
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