ID GLNA_CRIGR Reviewed; 373 AA. AC P04773; Q9EQP8; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 04-NOV-2026, entry version 135. DE RecName: Full=Glutamine synthetase {ECO:0000303|PubMed:2868445}; DE Short=GS {ECO:0000303|PubMed:2868445}; DE EC=6.3.1.2 {ECO:0000250|UniProtKB:P15104}; DE AltName: Full=Glutamate--ammonia ligase {ECO:0000305}; DE AltName: Full=Palmitoyltransferase GLUL {ECO:0000305}; DE EC=2.3.1.225 {ECO:0000250|UniProtKB:P15104}; GN Name=GLUL {ECO:0000250|UniProtKB:P15104}; OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; OC Cricetidae; Cricetinae; Cricetulus. OX NCBI_TaxID=10029; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Ovary; RX PubMed=2868445; DOI=10.1093/nar/14.2.999; RA Hayward B.E., Hussain A., Wilson R.H., Lyons A., Woodcock V., McIntosh B., RA Harris T.J.R.; RT "The cloning and nucleotide sequence of cDNA for an amplified glutamine RT synthetase gene from the Chinese hamster."; RL Nucleic Acids Res. 14:999-1008(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Tong Y., Wang H.; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Glutamine synthetase that catalyzes the ATP-dependent CC conversion of glutamate and ammonia to glutamine. Its role depends on CC tissue localization: in the brain, it regulates the levels of toxic CC ammonia and converts neurotoxic glutamate to harmless glutamine, CC whereas in the liver, it is one of the enzymes responsible for the CC removal of ammonia. Plays a key role in ammonium detoxification during CC erythropoiesis: the glutamine synthetase activity is required to remove CC ammonium generated by porphobilinogen deaminase (HMBS) during heme CC biosynthesis to prevent ammonium accumulation and oxidative stress (By CC similarity). Essential for proliferation of fetal skin fibroblasts (By CC similarity). Independently of its glutamine synthetase activity, CC required for endothelial cell migration during vascular development (By CC similarity). Involved in angiogenesis by regulating membrane CC localization and activation of the GTPase RHOJ, possibly by promoting CC RHOJ palmitoylation. May act as a palmitoyltransferase for RHOJ: able CC to autopalmitoylate and then transfer the palmitoyl group to RHOJ. CC Plays a role in ribosomal 40S subunit biogenesis. Through the CC interaction with BEST2, inhibits BEST2 channel activity by affecting CC the gating at the aperture in the absence of intracellular L-glutamate, CC but sensitizes BEST2 to intracellular L-glutamate, which promotes the CC opening of BEST2 and thus relieves its inhibitory effect on BEST2 (By CC similarity). {ECO:0000250|UniProtKB:P15104, CC ECO:0000250|UniProtKB:P15105}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-glutamate + NH4(+) + ATP = L-glutamine + ADP + phosphate + CC H(+); Xref=Rhea:RHEA:16169, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.1.2; CC Evidence={ECO:0000250|UniProtKB:P15104}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-cysteinyl-[protein] + hexadecanoyl-CoA = S-hexadecanoyl-L- CC cysteinyl-[protein] + CoA; 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:0000250|UniProtKB:P15104}; 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:0000250|UniProtKB:P15104}; CC -!- ACTIVITY REGULATION: Glutamine synthetase activity is inhibited by CC methionine sulfoximine (MSO). {ECO:0000250|UniProtKB:P15104}. CC -!- SUBUNIT: Decamer; composed of two pentamers (By similarity). Interacts CC with PALMD (By similarity). Interacts with RHOJ (By similarity). CC Interacts with BEST2; this interaction tethers a fraction of GLUL to CC the membrane, causing a decrease of cytosolic glutamine synthase (GS) CC activity and inhibits the chloride channel activity of BEST2 by CC affecting the gating at the aperture in the absence of intracellular CC glutamate (By similarity). {ECO:0000250|UniProtKB:P15104, CC ECO:0000250|UniProtKB:P15105}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P15104}. Microsome CC {ECO:0000250|UniProtKB:P09606}. Mitochondrion CC {ECO:0000250|UniProtKB:P09606}. Cell membrane CC {ECO:0000250|UniProtKB:P15104}; Lipid-anchor CC {ECO:0000250|UniProtKB:P15104}. Note=Mainly localizes in the cytosol, CC with a fraction associated with the cell membrane. CC {ECO:0000250|UniProtKB:P15104}. CC -!- PTM: Palmitoylated; undergoes autopalmitoylation. CC {ECO:0000250|UniProtKB:P15104}. CC -!- PTM: Acetylated by EP300/p300; acetylation is stimulated by increased CC glutamine levels and promotes ubiquitin-mediated proteasomal CC degradation. {ECO:0000250|UniProtKB:P15104}. CC -!- PTM: Ubiquitinated by ZNRF1 (By similarity). Ubiquitinated by the DCX CC (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CC CRL4(CRBN), leading to proteasomal degradation (By similarity). CC {ECO:0000250|UniProtKB:P15104, ECO:0000250|UniProtKB:P15105}. CC -!- SIMILARITY: Belongs to the glutamine synthetase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X03495; CAA27211.1; -; mRNA. DR EMBL; AF150961; AAG43362.1; -; mRNA. DR AlphaFoldDB; P04773; -. DR SMR; P04773; -. DR GeneID; 100689337; -. DR KEGG; cge:100689337; -. DR eggNOG; KOG0683; Eukaryota. DR OMA; AADEMWM; -. DR OrthoDB; 1936100at2759; -. DR Proteomes; UP001108280; Chromosome 1. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0004356; F:glutamine synthetase activity; ISS:UniProtKB. DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; ISS:UniProtKB. DR GO; GO:0097275; P:intracellular ammonium homeostasis; ISS:UniProtKB. DR GO; GO:1901704; P:L-glutamine biosynthetic process; IEA:InterPro. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0018345; P:protein palmitoylation; ISS:UniProtKB. DR GO; GO:0010594; P:regulation of endothelial cell migration; ISS:UniProtKB. DR GO; GO:1903670; P:regulation of sprouting angiogenesis; ISS:UniProtKB. DR FunFam; 3.10.20.70:FF:000004; Glutamine synthetase; 1. DR FunFam; 3.30.590.10:FF:000011; Glutamine synthetase; 1. DR Gene3D; 3.10.20.70; Glutamine synthetase, N-terminal domain; 1. DR Gene3D; 3.30.590.10; Glutamine synthetase/guanido kinase, catalytic domain; 1. DR InterPro; IPR008147; Gln_synt_N. DR InterPro; IPR036651; Gln_synt_N_sf. 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 InterPro; IPR050292; Glutamine_Synthetase. DR PANTHER; PTHR20852; GLUTAMINE SYNTHETASE; 1. DR PANTHER; PTHR20852:SF45; GLUTAMINE SYNTHETASE; 1. DR Pfam; PF00120; Gln-synt_C; 1. DR Pfam; PF03951; Gln-synt_N; 1. DR SMART; SM01230; Gln-synt_C; 1. DR SUPFAM; SSF54368; Glutamine synthetase, N-terminal domain; 1. DR SUPFAM; SSF55931; Glutamine synthetase/guanido kinase; 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 2: Evidence at transcript level; KW Acetylation; Angiogenesis; ATP-binding; Cell membrane; Cytoplasm; KW Endoplasmic reticulum; Ligase; Lipoprotein; Magnesium; Manganese; Membrane; KW Metal-binding; Microsome; Mitochondrion; Nucleotide-binding; Palmitate; KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P15105" FT CHAIN 2..373 FT /note="Glutamine synthetase" FT /id="PRO_0000153138" 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 REGION 2..25 FT /note="Required for glutamine-induced ubiquitination by FT CRL4(CRBN) and proteasomal degradation" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 134 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 134 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 136 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 196 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 203..208 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 203 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15104" 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:0000250|UniProtKB:P15104" FT BINDING 255..257 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 319 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P15104" 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:0000250|UniProtKB:P15104" FT BINDING 336..338 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P15104" FT BINDING 338 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P15104" 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-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P15105" FT MOD_RES 11 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P15104" FT MOD_RES 14 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P15104" FT MOD_RES 104 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P15105" FT MOD_RES 343 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P15104" FT CONFLICT 12 FT /note="G -> N (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 18..19 FT /note="MS -> LC (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 72 FT /note="S -> G (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 91..92 FT /note="KE -> RD (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 106 FT /note="Q -> R (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 116 FT /note="T -> S (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 140 FT /note="L -> M (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 152 FT /note="D -> N (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 160 FT /note="L -> P (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 172 FT /note="R -> G (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 176 FT /note="M -> V (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 194 FT /note="Y -> N (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 198..199 FT /note="KH -> MP (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 230 FT /note="K -> E (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 240 FT /note="S -> P (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 260 FT /note="T -> A (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 271 FT /note="K -> E (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 299 FT /note="R -> G (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 305 FT /note="K -> E (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 318 FT /note="D -> N (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 339..341 FT /note="ARC -> DRR (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" FT CONFLICT 367 FT /note="Q -> E (in Ref. 2; CAA27211)" FT /evidence="ECO:0000305" SQ SEQUENCE 373 AA; 42320 MW; 611D58CE20FB16CF CRC64; MATSASSHLN KGIKQMYMSL PQGEKVQAMY IWVDGTGEGL RCKTRTLDCE PKCVEELPEW NFDGSSTFQS ESSNSDMYLS PVAMFRDPFR KEPNKLVFCE VFKYNQKPAE TNLRHTCKRI MDMVSNQHPW FGMEQEYTLL GTDGHPFGWP SDGFPGPQGL YYCGVGADKA YRRDIMEAHY RACLYAGVKI TGTYAEVKHA QWEFQIGPCE GIRMGDHLWV ARFILHRVCK DFGVIATFDS KPIPGNWNGA GCHTNFSTKT MREENGLKHI KEAIEKLSKR HRYHIRAYDP KGGLDNARRL TGFHKTSNIN DFSAGVADRS ASIRIPRTVG QEKKGYFEAR CPSANCDPFA VTEAIVRTCL LNETGDQPFQ YKN //