GLNA_CANLF
ID GLNA_CANLF Reviewed; 373 AA.
AC Q8HZM5; Q8HZM4;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Glutamine synthetase {ECO:0000303|PubMed:12749766};
DE Short=GS {ECO:0000303|PubMed:12749766};
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=12749766; DOI=10.1042/bj20030132;
RA Shin D., Park S., Park C.;
RT "A splice variant acquiring an extra transcript leader region decreases the
RT translation of glutamine synthetase gene.";
RL Biochem. J. 374:175-184(2003).
RN [2] {ECO:0007744|PDB:2UU7}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH MAGNESIUM, AND
RP 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).
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:0000269|PubMed:18005987};
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 (PubMed:18005987).
CC Interacts with PALMD (By similarity). Interacts with RHOJ (By
CC similarity). {ECO:0000250|UniProtKB:P15104,
CC ECO:0000250|UniProtKB:P15105, ECO:0000269|PubMed:18005987}.
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; AF544242; AAN41001.1; -; mRNA.
DR EMBL; AF544243; AAN41002.1; -; Genomic_DNA.
DR RefSeq; NP_001002965.2; NM_001002965.2.
DR RefSeq; NP_001280153.1; NM_001293224.1.
DR PDB; 2UU7; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=2-373.
DR PDBsum; 2UU7; -.
DR AlphaFoldDB; Q8HZM5; -.
DR SMR; Q8HZM5; -.
DR STRING; 9612.ENSCAFP00000032533; -.
DR PaxDb; Q8HZM5; -.
DR PRIDE; Q8HZM5; -.
DR GeneID; 403443; -.
DR KEGG; cfa:403443; -.
DR CTD; 2752; -.
DR eggNOG; KOG0683; Eukaryota.
DR HOGENOM; CLU_036762_1_1_1; -.
DR InParanoid; Q8HZM5; -.
DR OrthoDB; 784869at2759; -.
DR BRENDA; 6.3.1.2; 1153.
DR SABIO-RK; Q8HZM5; -.
DR EvolutionaryTrace; Q8HZM5; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:glutamate-ammonia ligase 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; IBA:GO_Central.
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; -; 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; Endoplasmic reticulum; Ligase; Lipoprotein; Magnesium;
KW 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_0000153137"
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:0000269|PubMed:18005987,
FT ECO:0007744|PDB:2UU7"
FT BINDING 196
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18005987,
FT ECO:0007744|PDB:2UU7"
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:0000269|PubMed:18005987,
FT ECO:0007744|PDB:2UU7"
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 HELIX 6..8
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 11..18
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 40..49
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 64..67
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 76..86
FT /evidence="ECO:0007829|PDB:2UU7"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 114..122
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 123..127
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 130..140
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:2UU7"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 173..186
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 213..232
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 251..257
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:2UU7"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 267..278
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 281..287
FT /evidence="ECO:0007829|PDB:2UU7"
FT TURN 290..295
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:2UU7"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 321..325
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 327..332
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:2UU7"
FT HELIX 348..359
FT /evidence="ECO:0007829|PDB:2UU7"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:2UU7"
SQ SEQUENCE 373 AA; 42028 MW; E5AD18AEED3F0C52 CRC64;
MATSASSHLN KGIKQVYMSL PQGEKVQAMY IWIDGTGEGL RCKTRTLDSE PKGVEELPEW
NFDGSSTFQS EGSNSDMYLV PAAMFRDPFR KDPNKLVFCE VFKYNRKPAE TNLRHTCKRI
MDMVSNQHPW FGMEQEYTLM GTDGHPFGWP SNGFPGPQGP YYCGVGADKA YGRDIVEAHY
RACLYAGIKI AGTNAEVMPA QWEFQIGPCE GIDMGDHLWV ARFILHRVCE DFGVIATFDP
KPIPGNWNGA GCHTNFSTKA MREENGLKYI EESIEKLSKR HQYHIRAYDP KGGLDNARRL
TGFHETSNIN DFSAGVANRG ASIRIPRTVG QEKKGYFEDR RPSANCDPFS VTEALIRTCL
LNETGDEPFQ YKN
