GLNA_RAT
ID GLNA_RAT Reviewed; 373 AA.
AC P09606; Q6P7Q9;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Glutamine synthetase {ECO:0000303|PubMed:2901064};
DE Short=GS {ECO:0000303|PubMed:2901064};
DE EC=6.3.1.2 {ECO:0000269|PubMed:28323};
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:0000312|RGD:2710}; Synonyms=Glns;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=2901064; DOI=10.1093/nar/16.15.7726;
RA van de Zande L., Labruyere W., Smaling M., Moorman A., Wilson R.H.,
RA Charles R., Lamers W.H.;
RT "Nucleotide sequence of rat glutamine synthetase mRNA.";
RL Nucleic Acids Res. 16:7726-7726(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=1970548; DOI=10.1016/0378-1119(90)90306-c;
RA van de Zande L., Labruyere W.T., Arnberg A.C., Wilson R.H.,
RA van de Bogaert A.J.W., Das A.T., van Oorschot D.A.J., Frijters C.,
RA Charles R., Moorman A.F.M., Lamers W.H.;
RT "Isolation and characterization of the rat glutamine synthetase-encoding
RT gene.";
RL Gene 87:225-232(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1674354; DOI=10.1016/0169-328x(91)90003-g;
RA Mill J.F., Mearow K.M., Purohit H.J., Haleem-Smith H., King R., Freese E.;
RT "Cloning and functional characterization of the rat glutamine synthetase
RT gene.";
RL Brain Res. Mol. Brain Res. 9:197-207(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Brown Norway; TISSUE=Heart, and Pituitary;
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 [5]
RP PROTEIN SEQUENCE OF 15-41; 92-103; 190-213; 299-319 AND 341-357, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=4403443; DOI=10.1016/s0021-9258(20)81106-5;
RA Tate S.S., Leu F.Y., Meister A.;
RT "Rat liver glutamine synthetase. Preparation, properties, and mechanism of
RT inhibition by carbamyl phosphate.";
RL J. Biol. Chem. 247:5312-5321(1972).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28323; DOI=10.1016/s0021-9258(17)34587-8;
RA Deuel T.F., Louie M., Lerner A.;
RT "Glutamine synthetase from rat liver. Purification, properties, and
RT preparation of specific antisera.";
RL J. Biol. Chem. 253:6111-6118(1978).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=6138251; DOI=10.1002/j.1460-2075.1983.tb01464.x;
RA Gebhardt R., Mecke D.;
RT "Heterogeneous distribution of glutamine synthetase among rat liver
RT parenchymal cells in situ and in primary culture.";
RL EMBO J. 2:567-570(1983).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=7638749; DOI=10.1016/s0039-6060(05)80341-1;
RA Abcouwer S.F., Lukascewicz G.C., Ryan U.S., Souba W.W.;
RT "Molecular regulation of lung endothelial glutamine synthetase
RT expression.";
RL Surgery 118:325-334(1995).
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).
CC -!- FUNCTION: Glutamine synthetase that catalyzes the ATP-dependent
CC conversion of glutamate and ammonia to glutamine (PubMed:28323). Its
CC role depends on tissue localization: in the brain, it regulates the
CC levels of toxic ammonia and converts neurotoxic glutamate to harmless
CC glutamine, whereas in the liver, it is one of the enzymes responsible
CC for the removal of ammonia (By similarity). Essential for proliferation
CC of fetal skin fibroblasts. Independently of its glutamine synthetase
CC activity, required for endothelial cell migration during vascular
CC development: acts by regulating membrane localization and activation of
CC the GTPase RHOJ, possibly by promoting RHOJ palmitoylation. May act as
CC a palmitoyltransferase for RHOJ: able to autopalmitoylate and then
CC transfer the palmitoyl group to RHOJ (By similarity). Plays a role in
CC ribosomal 40S subunit biogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P15104, ECO:0000250|UniProtKB:P15105,
CC ECO:0000269|PubMed:28323}.
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:28323};
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:0000250|UniProtKB:P15104};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:28323};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:28323};
CC -!- ACTIVITY REGULATION: Glutamine synthetase activity is inhibited by
CC methionine sulfoximine (MSO). {ECO:0000269|PubMed:4403443}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 mM for L-glutamate (with 2 mM of Mn(2+))
CC {ECO:0000269|PubMed:28323};
CC KM=0.3 mM for L-glutamate (with 8 mM of Mn(2+))
CC {ECO:0000269|PubMed:28323};
CC KM=1.6 mM for L-glutamate (with 50 mM of Mg(2+))
CC {ECO:0000269|PubMed:28323};
CC KM=5.0 mM for L-glutamate (with 10 mM of Mg(2+))
CC {ECO:0000269|PubMed:28323};
CC KM=0.3 mM for NH(3) {ECO:0000269|PubMed:28323};
CC -!- SUBUNIT: Decamer; composed of two pentamers (By similarity). Interacts
CC with PALMD (By similarity). Interacts with RHOJ (By similarity).
CC {ECO:0000250|UniProtKB:P15104, ECO:0000250|UniProtKB:P15105}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:28323}.
CC Microsome {ECO:0000305|PubMed:28323}. Mitochondrion
CC {ECO:0000305|PubMed:28323}. 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 -!- TISSUE SPECIFICITY: In the adult liver, expression is restricted to a
CC small population of hepatocytes which form only a small rim of one to
CC three hepatocytes around the central veins (PubMed:6138251). Expressed
CC in lung microvascular endothelial cells (PubMed:7638749).
CC {ECO:0000269|PubMed:6138251, ECO:0000269|PubMed:7638749}.
CC -!- INDUCTION: By glucocorticoids (PubMed:18555765). Stimulated by the N-
CC methyl-D-aspartate (NMDA) type glutamate receptor antagonist MK801
CC (PubMed:18555765). Vitamin D and the Wnt signaling pathway inhibit its
CC expression and activity (PubMed:18555765). Down-regulated during
CC osteoblast mineralization (PubMed:18555765).
CC {ECO:0000269|PubMed:18555765}.
CC -!- PTM: Palmitoylated; undergoes autopalmitoylation.
CC {ECO:0000250|UniProtKB:P15104}.
CC -!- PTM: Ubiquitinated by ZNRF1. {ECO:0000250|UniProtKB:P15105}.
CC -!- SIMILARITY: Belongs to the glutamine synthetase family. {ECO:0000305}.
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DR EMBL; X07921; CAA30754.1; -; mRNA.
DR EMBL; M29599; AAA65096.1; -; Genomic_DNA.
DR EMBL; M29595; AAA65096.1; JOINED; Genomic_DNA.
DR EMBL; M29596; AAA65096.1; JOINED; Genomic_DNA.
DR EMBL; M29597; AAA65096.1; JOINED; Genomic_DNA.
DR EMBL; M29598; AAA65096.1; JOINED; Genomic_DNA.
DR EMBL; M29579; AAA65095.1; -; mRNA.
DR EMBL; M91652; AAC42038.1; -; mRNA.
DR EMBL; BC061559; AAH61559.1; -; mRNA.
DR EMBL; BC072694; AAH72694.1; -; mRNA.
DR PIR; S01242; AJRTQ.
DR RefSeq; NP_058769.4; NM_017073.3.
DR AlphaFoldDB; P09606; -.
DR SMR; P09606; -.
DR BioGRID; 247058; 4.
DR IntAct; P09606; 3.
DR MINT; P09606; -.
DR STRING; 10116.ENSRNOP00000065890; -.
DR CarbonylDB; P09606; -.
DR iPTMnet; P09606; -.
DR PhosphoSitePlus; P09606; -.
DR SwissPalm; P09606; -.
DR World-2DPAGE; 0004:P09606; -.
DR PaxDb; P09606; -.
DR PRIDE; P09606; -.
DR GeneID; 24957; -.
DR KEGG; rno:24957; -.
DR CTD; 2752; -.
DR RGD; 2710; Glul.
DR VEuPathDB; HostDB:ENSRNOG00000049560; -.
DR eggNOG; KOG0683; Eukaryota.
DR HOGENOM; CLU_036762_1_1_1; -.
DR InParanoid; P09606; -.
DR OMA; DRRPNAN; -.
DR OrthoDB; 784869at2759; -.
DR PhylomeDB; P09606; -.
DR BRENDA; 6.3.1.2; 5301.
DR Reactome; R-RNO-210455; Astrocytic Glutamate-Glutamine Uptake And Metabolism.
DR Reactome; R-RNO-8964539; Glutamate and glutamine metabolism.
DR PRO; PR:P09606; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000049560; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; P09606; RN.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0044297; C:cell body; ISO:RGD.
DR GO; GO:0042995; C:cell projection; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0043209; C:myelin sheath; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0045503; F:dynein light chain binding; IPI:RGD.
DR GO; GO:0016595; F:glutamate binding; IDA:RGD.
DR GO; GO:0004356; F:glutamate-ammonia ligase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0000287; F:magnesium ion binding; IDA:RGD.
DR GO; GO:0030145; F:manganese ion binding; IDA:RGD.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; ISS:UniProtKB.
DR GO; GO:0019676; P:ammonia assimilation cycle; IDA:RGD.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
DR GO; GO:0006536; P:glutamate metabolic process; IDA:RGD.
DR GO; GO:0006542; P:glutamine biosynthetic process; IDA:RGD.
DR GO; GO:0042133; P:neurotransmitter metabolic process; TAS:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:RGD.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IMP:RGD.
DR GO; GO:0018345; P:protein palmitoylation; ISS:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:1904749; P:regulation of protein localization to nucleolus; ISO:RGD.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0009749; P:response to glucose; ISO:RGD.
DR GO; GO:0042254; P:ribosome biogenesis; ISO:RGD.
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 Acetylation; Angiogenesis; ATP-binding; Cell membrane; Cytoplasm;
KW Direct protein sequencing; 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:0000250|UniProtKB:P15105"
FT CHAIN 2..373
FT /note="Glutamine synthetase"
FT /id="PRO_0000153143"
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: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 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 74
FT /note="N -> D (in Ref. 4; AAH61559)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="H -> R (in Ref. 3; AAC42038)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 42268 MW; A7C12D9C5959BCA1 CRC64;
MATSASSHLN KGIKQMYMNL PQGEKIQLMY IWVDGTGEGL RCKTRTLDCD PKCVEELPEW
NFDGSSTFQS EGSNSDMYLH PVAMFRDPFR RDPNKLVFCE VFKYNRKPAE TNLRHSCKRI
MDMVSSQHPW FGMEQEYTLM GTDGHPFGWP SNGFPGPQGP YYCGVGADKA YGRDIVEAHY
RACLYAGIKI TGTNAEVMPA QWEFQIGPCE GIRMGDHLWV ARFILHRVCE DFGVIATFDP
KPIPGNWNGA GCHTNFSTKA MREENGLRCI EEAIDKLSKR HQYHIRAYDP KGGLDNARRL
TGFHETSNIN DFSAGVANRS ASIRIPRIVG QEKKGYFEDR RPSANCDPYA VTEAIVRTCL
LNETGDEPFQ YKN
