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Protein

Glutamine synthetase

Gene

GLUL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.By similarity1 Publication

Catalytic activityi

ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine.
L-glutamate = 4-aminobutanoate + CO2.

Cofactori

Protein has several cofactor binding sites:

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLigase, Lyase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS06066-MONOMER.
BRENDAi6.3.1.2. 2681.
ReactomeiR-HSA-210455. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
R-HSA-70614. Amino acid synthesis and interconversion (transamination).
SABIO-RKiP15104.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamine synthetase (EC:6.3.1.2)
Short name:
GS
Alternative name(s):
Glutamate decarboxylase (EC:4.1.1.15)
Glutamate--ammonia ligase
Gene namesi
Name:GLUL
Synonyms:GLNS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000135821.16.
HGNCiHGNC:4341. GLUL.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Congenital systemic glutamine deficiency (CSGD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine is largely absent from affected patients serum, urine and cerebrospinal fluid.
See also OMIM:610015
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026560324R → C in CSGD; reduced glutamine synthetase activity. 1 PublicationCorresponds to variant dbSNP:rs80358214Ensembl.1
Natural variantiVAR_026561341R → C in CSGD; suggests reduced glutamine synthetase activity. 1 PublicationCorresponds to variant dbSNP:rs80358215Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2752.
MalaCardsiGLUL.
MIMi610015. phenotype.
OpenTargetsiENSG00000135821.
Orphaneti71278. Congenital brain dysgenesis due to glutamine synthetase deficiency.
PharmGKBiPA28743.

Chemistry databases

ChEMBLiCHEMBL4612.
DrugBankiDB06774. Capsaicin.
DB01212. Ceftriaxone.
DB01119. Diazoxide.
DB08794. Ethyl biscoumacetate.
DB00142. L-Glutamic Acid.
DB00130. L-Glutamine.
DB00134. L-Methionine.
DB00082. Pegvisomant.
DB00466. Picrotoxin.

Polymorphism and mutation databases

BioMutaiGLUL.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001531392 – 373Glutamine synthetaseAdd BLAST372

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei104PhosphotyrosineBy similarity1
Modified residuei343PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated by ZNRF1.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP15104.
MaxQBiP15104.
PaxDbiP15104.
PeptideAtlasiP15104.
PRIDEiP15104.

2D gel databases

REPRODUCTION-2DPAGEiIPI00010130.
UCD-2DPAGEiP15104.

PTM databases

iPTMnetiP15104.
PhosphoSitePlusiP15104.

Expressioni

Developmental stagei

Expressed during early fetal stages.1 Publication

Inductioni

By glucocorticoids. Vitamin D and the Wnt signaling pathway inhibit its expression and activity.1 Publication

Gene expression databases

BgeeiENSG00000135821.
CleanExiHS_GLUL.
ExpressionAtlasiP15104. baseline and differential.
GenevisibleiP15104. HS.

Organism-specific databases

HPAiCAB008636.
HPA007316.
HPA007571.

Interactioni

Subunit structurei

Homooctamer and homotetramer. Interacts with PALMD (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • dynein light chain binding Source: Ensembl
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi109014. 35 interactors.
DIPiDIP-308N.
IntActiP15104. 25 interactors.
MINTiMINT-1183856.
STRINGi9606.ENSP00000307900.

Chemistry databases

BindingDBiP15104.

Structurei

Secondary structure

1373
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 8Combined sources4
Helixi11 – 18Combined sources8
Beta strandi26 – 33Combined sources8
Beta strandi40 – 49Combined sources10
Helixi54 – 56Combined sources3
Beta strandi60 – 63Combined sources4
Turni64 – 68Combined sources5
Beta strandi69 – 71Combined sources3
Helixi72 – 74Combined sources3
Beta strandi76 – 86Combined sources11
Turni88 – 90Combined sources3
Beta strandi95 – 102Combined sources8
Beta strandi106 – 108Combined sources3
Helixi114 – 123Combined sources10
Helixi124 – 127Combined sources4
Beta strandi130 – 140Combined sources11
Beta strandi144 – 146Combined sources3
Beta strandi158 – 160Combined sources3
Turni167 – 169Combined sources3
Helixi173 – 186Combined sources14
Beta strandi190 – 195Combined sources6
Beta strandi201 – 210Combined sources10
Helixi213 – 232Combined sources20
Beta strandi235 – 237Combined sources3
Beta strandi245 – 247Combined sources3
Beta strandi251 – 257Combined sources7
Helixi259 – 262Combined sources4
Turni264 – 266Combined sources3
Helixi267 – 278Combined sources12
Helixi281 – 287Combined sources7
Turni290 – 295Combined sources6
Helixi296 – 298Combined sources3
Beta strandi314 – 316Combined sources3
Beta strandi321 – 325Combined sources5
Helixi327 – 332Combined sources6
Beta strandi337 – 339Combined sources3
Helixi348 – 359Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OJWX-ray2.05A/B/C/D/E5-365[»]
2QC8X-ray2.60A/B/C/D/E/F/G/H/I/J5-365[»]
ProteinModelPortaliP15104.
SMRiP15104.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15104.

Family & Domainsi

Sequence similaritiesi

Belongs to the glutamine synthetase family.Curated

Phylogenomic databases

eggNOGiKOG0683. Eukaryota.
COG0174. LUCA.
GeneTreeiENSGT00390000010047.
HOGENOMiHOG000061500.
HOVERGENiHBG005847.
InParanoidiP15104.
KOiK01915.
OMAiMMPDGVT.
OrthoDBiEOG091G07E9.
PhylomeDBiP15104.
TreeFamiTF300491.

Family and domain databases

Gene3Di3.30.590.10. 1 hit.
InterProiView protein in InterPro
IPR008147. Gln_synt_b-grasp.
IPR036651. Gln_synt_N.
IPR014746. Gln_synth/guanido_kin_cat_dom.
IPR008146. Gln_synth_cat_dom.
IPR027303. Gln_synth_gly_rich_site.
IPR027302. Gln_synth_N_conserv_site.
PfamiView protein in Pfam
PF00120. Gln-synt_C. 1 hit.
PF03951. Gln-synt_N. 1 hit.
SMARTiView protein in SMART
SM01230. Gln-synt_C. 1 hit.
SUPFAMiSSF54368. SSF54368. 1 hit.
SSF55931. SSF55931. 1 hit.
PROSITEiView protein in PROSITE
PS00180. GLNA_1. 1 hit.
PS00181. GLNA_ATP. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P15104-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTSASSHLN KGIKQVYMSL PQGEKVQAMY IWIDGTGEGL RCKTRTLDSE
60 70 80 90 100
PKCVEELPEW NFDGSSTLQS EGSNSDMYLV PAAMFRDPFR KDPNKLVLCE
110 120 130 140 150
VFKYNRRPAE TNLRHTCKRI MDMVSNQHPW FGMEQEYTLM GTDGHPFGWP
160 170 180 190 200
SNGFPGPQGP YYCGVGADRA YGRDIVEAHY RACLYAGVKI AGTNAEVMPA
210 220 230 240 250
QWEFQIGPCE GISMGDHLWV ARFILHRVCE DFGVIATFDP KPIPGNWNGA
260 270 280 290 300
GCHTNFSTKA MREENGLKYI EEAIEKLSKR HQYHIRAYDP KGGLDNARRL
310 320 330 340 350
TGFHETSNIN DFSAGVANRS ASIRIPRTVG QEKKGYFEDR RPSANCDPFS
360 370
VTEALIRTCL LNETGDEPFQ YKN
Length:373
Mass (Da):42,064
Last modified:January 23, 2007 - v4
Checksum:i45390C100924FAF3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7S → Y in AAH31964 (PubMed:15489334).Curated1
Sequence conflicti154F → L in CAD97626 (PubMed:17974005).Curated1
Sequence conflicti155P → T in AAH31964 (PubMed:15489334).Curated1
Sequence conflicti314A → G in CAA68457 (PubMed:2888076).Curated1
Sequence conflicti322 – 323SI → RL in CAA42495 (PubMed:1681907).Curated2
Sequence conflicti347D → E in CAA42495 (PubMed:1681907).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026560324R → C in CSGD; reduced glutamine synthetase activity. 1 PublicationCorresponds to variant dbSNP:rs80358214Ensembl.1
Natural variantiVAR_026561341R → C in CSGD; suggests reduced glutamine synthetase activity. 1 PublicationCorresponds to variant dbSNP:rs80358215Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00387 mRNA. Translation: CAA68457.1.
X59834 mRNA. Translation: CAA42495.1.
S70290 mRNA. Translation: AAB30693.1.
AY486122 mRNA. Translation: AAS57904.1.
AY486123 Genomic DNA. Translation: AAS57905.1.
BX537384 mRNA. Translation: CAD97626.1.
AL139344 Genomic DNA. No translation available.
BC010037 mRNA. Translation: AAH10037.1.
BC011700 mRNA. Translation: AAH11700.1.
BC011852 mRNA. Translation: AAH11852.1.
BC018992 mRNA. Translation: AAH18992.1.
BC031964 mRNA. Translation: AAH31964.1.
BC051726 mRNA. Translation: AAH51726.1.
CCDSiCCDS1344.1.
PIRiS18455. AJHUQ.
RefSeqiNP_001028216.1. NM_001033044.3.
NP_001028228.1. NM_001033056.3.
NP_002056.2. NM_002065.6.
XP_006711341.1. XM_006711278.1.
UniGeneiHs.132016.
Hs.518525.

Genome annotation databases

EnsembliENST00000311223; ENSP00000307900; ENSG00000135821.
ENST00000331872; ENSP00000356537; ENSG00000135821.
ENST00000339526; ENSP00000344958; ENSG00000135821.
ENST00000417584; ENSP00000398320; ENSG00000135821.
GeneIDi2752.
KEGGihsa:2752.
UCSCiuc001gpa.3. human.

Similar proteinsi

Entry informationi

Entry nameiGLNA_HUMAN
AccessioniPrimary (citable) accession number: P15104
Secondary accession number(s): Q499Y9
, Q5T9Z1, Q7Z3W4, Q8IZ17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 23, 2007
Last modified: October 25, 2017
This is version 194 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families