ID   GLNA_MACFA              Reviewed;         374 AA.
AC   Q4R7U3;
DT   16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   24-JAN-2024, entry version 85.
DE   RecName: Full=Glutamine synthetase {ECO:0000250|UniProtKB:P15104};
DE            Short=GS {ECO:0000250|UniProtKB:P09606};
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};
GN   ORFNames=QtsA-14381 {ECO:0000303|Ref.1};
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Glutamine synthetase that catalyzes the ATP-dependent
CC       conversion of glutamate and ammonia to glutamine (By similarity). 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   -!- 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:0000250|UniProtKB:P15104};
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: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       {ECO:0000250|UniProtKB:P15104, 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: Ubiquitinated by ZNRF1. {ECO:0000250|UniProtKB:P15105}.
CC   -!- SIMILARITY: Belongs to the glutamine synthetase family. {ECO:0000305}.
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DR   EMBL; AB168719; BAE00829.1; -; mRNA.
DR   RefSeq; NP_001270340.1; NM_001283411.1.
DR   AlphaFoldDB; Q4R7U3; -.
DR   SMR; Q4R7U3; -.
DR   STRING; 9541.ENSMFAP00000001626; -.
DR   eggNOG; KOG0683; Eukaryota.
DR   OrthoDB; 1115057at2759; -.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004356; F:glutamine synthetase activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0006542; P:glutamine biosynthetic process; IEA:InterPro.
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   Gene3D; 3.10.20.70; Glutamine synthetase, N-terminal domain; 1.
DR   Gene3D; 3.30.590.10; Glutamine synthetase/guanido kinase, catalytic domain; 2.
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   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   Angiogenesis; ATP-binding; Cell membrane; Cytoplasm; Endoplasmic reticulum;
KW   Ligase; Lipoprotein; Magnesium; Manganese; Membrane; Metal-binding;
KW   Microsome; Mitochondrion; Nucleotide-binding; Palmitate; Phosphoprotein;
KW   Reference proteome; Transferase; Ubl conjugation.
FT   CHAIN           1..374
FT                   /note="Glutamine synthetase"
FT                   /id="PRO_0000153140"
FT   DOMAIN          24..106
FT                   /note="GS beta-grasp"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01330"
FT   DOMAIN          114..374
FT                   /note="GS catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01331"
FT   BINDING         135
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         135
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         137
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         197
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         204..209
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         204
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         247..248
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN39"
FT   BINDING         254
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         256..258
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         320
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         320
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN39"
FT   BINDING         325
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         337..339
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         339
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
FT   BINDING         341
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN39"
FT   MOD_RES         344
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P15104"
SQ   SEQUENCE   374 AA;  42023 MW;  6F2A0035CA38C68A CRC64;
     MTTSASSHLN KGIKQVYMSL PQGEKVQAMY IWIDGTGEGL RCKTRTLDSE PKCVEELPEW
     NFDGSSTLQS EGSNSDMYLV PAAMFRDPFR KDPNKLVLCE SFQVQFEGPA ETNLRHTCKR
     IMDMVSNQHP WFGMEQEYTL MGTDGHPFGW PSNGFPGPQG PYYCGVGADR AYGRDIVEAH
     YRACLYAGVK IAGTNAEVMP AQWEFQIGPC EGISMGDHLW VARFILHRVC EDFGVIATFD
     PKPIPGNWNG AGCHTNFSTK AMREENGLKY IEEAIEKLSK RHQYHIRAYD PKGGLDNARR
     LTGFHETSNI NDFSAGVANR SASIRIPRTV GQEKKGYFED RRPSANCDPF SVTEALIRTC
     LLNETGDEPF QYKN
//