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P15104 (GLNA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamine synthetase

Short name=GS
EC=6.3.1.2
Alternative name(s):
Glutamate decarboxylase
EC=4.1.1.15
Glutamate--ammonia ligase
Gene names
Name:GLUL
Synonyms:GLNS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length373 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9

Catalytic activity

ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine.

L-glutamate = 4-aminobutanoate + CO2.

Cofactor

Biotin By similarity.

Magnesium or manganese By similarity.

Subunit structure

Homooctamer and homotetramer. Interacts with PALMD By similarity. Ref.8

Subcellular location

Cytoplasm. Mitochondrion By similarity.

Developmental stage

Expressed during early fetal stages. Ref.9

Induction

By glucocorticoids. Vitamin D and the Wnt signaling pathway inhibit its expression and activity. Ref.10

Post-translational modification

Ubiquitinated by ZNRF1 By similarity.

Involvement in disease

Congenital systemic glutamine deficiency (CSGD) [MIM:610015]: Rare 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Sequence similarities

Belongs to the glutamine synthetase family.

Ontologies

Keywords
   Cellular componentCytoplasm
Mitochondrion
   DiseaseDisease mutation
   LigandATP-binding
Nucleotide-binding
   Molecular functionLigase
Lyase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell proliferation

Inferred from direct assay Ref.9. Source: UniProtKB

cellular amino acid biosynthetic process

Traceable author statement. Source: Reactome

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

glutamate catabolic process

Traceable author statement PubMed 21757002. Source: BHF-UCL

glutamine biosynthetic process

Traceable author statement PubMed 21757002. Source: BHF-UCL

neurotransmitter uptake

Traceable author statement. Source: Reactome

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentaxon terminus

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

perikaryon

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from electronic annotation. Source: Ensembl

rough endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

glutamate binding

Inferred from electronic annotation. Source: Ensembl

glutamate decarboxylase activity

Inferred from electronic annotation. Source: UniProtKB-EC

glutamate-ammonia ligase activity

Inferred from experiment. Source: Reactome

identical protein binding

Inferred from physical interaction PubMed 16189514PubMed 19447967PubMed 21988832. Source: IntAct

magnesium ion binding

Inferred from electronic annotation. Source: Ensembl

manganese ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself3EBI-746653,EBI-746653

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.11
Chain2 – 373372Glutamine synthetase
PRO_0000153139

Amino acid modifications

Modified residue21N-acetylthreonine Ref.11
Modified residue1041Phosphotyrosine By similarity

Natural variations

Natural variant3241R → C in CSGD; reduced glutamine synthetase activity. Ref.13
VAR_026560
Natural variant3411R → C in CSGD; suggests reduced glutamine synthetase activity. Ref.13
VAR_026561

Experimental info

Sequence conflict71S → Y in AAH31964. Ref.7
Sequence conflict1541F → L in CAD97626. Ref.5
Sequence conflict1551P → T in AAH31964. Ref.7
Sequence conflict3141A → G in CAA68457. Ref.1
Sequence conflict322 – 3232SI → RL in CAA42495. Ref.2
Sequence conflict3471D → E in CAA42495. Ref.2

Secondary structure

..................................................................... 373
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P15104 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 45390C100924FAF3

FASTA37342,064
        10         20         30         40         50         60 
MTTSASSHLN KGIKQVYMSL PQGEKVQAMY IWIDGTGEGL RCKTRTLDSE PKCVEELPEW 

        70         80         90        100        110        120 
NFDGSSTLQS EGSNSDMYLV PAAMFRDPFR KDPNKLVLCE VFKYNRRPAE TNLRHTCKRI 

       130        140        150        160        170        180 
MDMVSNQHPW FGMEQEYTLM GTDGHPFGWP SNGFPGPQGP YYCGVGADRA YGRDIVEAHY 

       190        200        210        220        230        240 
RACLYAGVKI AGTNAEVMPA QWEFQIGPCE GISMGDHLWV ARFILHRVCE DFGVIATFDP 

       250        260        270        280        290        300 
KPIPGNWNGA GCHTNFSTKA MREENGLKYI EEAIEKLSKR HQYHIRAYDP KGGLDNARRL 

       310        320        330        340        350        360 
TGFHETSNIN DFSAGVANRS ASIRIPRTVG QEKKGYFEDR RPSANCDPFS VTEALIRTCL 

       370 
LNETGDEPFQ YKN 

« Hide

References

« Hide 'large scale' references
[1]"Sequence of a human glutamine synthetase cDNA."
Gibbs C.S., Campbell K.E., Wilson R.H.
Nucleic Acids Res. 15:6293-6293(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"cDNA sequence of the long mRNA for human glutamine synthase."
van den Hoff M.J.B., Geerts W.J.C., Das A.T., Moorman A.F.M., Lamers W.H.
Biochim. Biophys. Acta 1090:249-251(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Overexpression of glutamine synthetase in human primary liver cancer."
Christa L., Simon M.T., Flinois J.P., Gebhardt R., Brechot C., Lasserre C.
Gastroenterology 106:1312-1320(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[4]Haberle J., Koch H.G.
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Retina.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain, Colon, Eye, Muscle and Testis.
[8]"Glutamine synthetase isolated from human brain: octameric structure and homology of partial primary structure with human liver glutamine synthetase."
Boksha I.S., Schonfeld H.J., Langen H., Muller F., Tereshkina E.B., Burbaeva G.S.H.
Biochemistry (Mosc.) 67:1012-1020(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain.
[9]"Glutamine synthetase is essential for proliferation of fetal skin fibroblasts."
Vermeulen T., Goerg B., Vogl T., Wolf M., Varga G., Toutain A., Paul R., Schliess F., Haeussinger D., Haeberle J.
Arch. Biochem. Biophys. 478:96-102(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[10]"Wnt and steroid pathways control glutamate signalling by regulating glutamine synthetase activity in osteoblastic cells."
Olkku A., Mahonen A.
Bone 43:483-493(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Congenital glutamine deficiency with glutamine synthetase mutations."
Haeberle J., Goerg B., Rutsch F., Schmidt E., Toutain A., Benoist J.-F., Gelot A., Suc A.-L., Hoehne W., Schliess F., Haeussinger D., Koch H.G.
N. Engl. J. Med. 353:1926-1933(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CSGD CYS-324 AND CYS-341, CHARACTERIZATION OF VARIANTS CSGD CYS-324 AND CYS-341.
+Additional computationally mapped references.

Web resources

Wikipedia

Glutamine synthetase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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. Translation: CAI19842.1.
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.
PIRAJHUQ. S18455.
RefSeqNP_001028216.1. NM_001033044.2.
NP_001028228.1. NM_001033056.2.
NP_002056.2. NM_002065.5.
UniGeneHs.518525.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2OJWX-ray2.05A/B/C/D/E5-364[»]
2QC8X-ray2.60A/B/C/D/E/F/G/H/I/J5-365[»]
ProteinModelPortalP15104.
SMRP15104. Positions 10-365.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109014. 20 interactions.
DIPDIP-308N.
IntActP15104. 18 interactions.
MINTMINT-1183856.
STRING9606.ENSP00000307900.

Chemistry

BindingDBP15104.
ChEMBLCHEMBL4612.
DrugBankDB00023. Asparaginase.
DB00142. L-Glutamic Acid.
DB00130. L-Glutamine.
DB00134. L-Methionine.

PTM databases

PhosphoSiteP15104.

2D gel databases

REPRODUCTION-2DPAGEIPI00010130.
UCD-2DPAGEP15104.

Proteomic databases

PaxDbP15104.
PeptideAtlasP15104.
PRIDEP15104.

Protocols and materials databases

DNASU2752.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311223; ENSP00000307900; ENSG00000135821.
ENST00000331872; ENSP00000356537; ENSG00000135821.
ENST00000339526; ENSP00000344958; ENSG00000135821.
ENST00000417584; ENSP00000398320; ENSG00000135821.
GeneID2752.
KEGGhsa:2752.
UCSCuc001gpa.2. human.

Organism-specific databases

CTD2752.
GeneCardsGC01M182350.
HGNCHGNC:4341. GLUL.
HPACAB008636.
HPA007316.
HPA007571.
MIM138290. gene.
610015. phenotype.
neXtProtNX_P15104.
Orphanet71278. Congenital brain dysgenesis due to glutamine synthetase deficiency.
PharmGKBPA28743.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0174.
HOGENOMHOG000061500.
HOVERGENHBG005847.
InParanoidP15104.
KOK01915.
OMAYGIDIEF.
OrthoDBEOG7CZK5G.
PhylomeDBP15104.
TreeFamTF300491.

Enzyme and pathway databases

BioCycMetaCyc:HS06066-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_13685. Neuronal System.
SABIO-RKP15104.

Gene expression databases

ArrayExpressP15104.
BgeeP15104.
CleanExHS_GLUL.
GenevestigatorP15104.

Family and domain databases

Gene3D3.30.590.10. 1 hit.
InterProIPR008147. Gln_synt_beta.
IPR014746. Gln_synth/guanido_kin_cat_dom.
IPR008146. Gln_synth_cat_dom.
IPR027303. Gln_synth_gly_rich_site.
IPR027302. Gln_synth_N_conserv_site.
[Graphical view]
PfamPF00120. Gln-synt_C. 1 hit.
PF03951. Gln-synt_N. 1 hit.
[Graphical view]
SUPFAMSSF54368. SSF54368. 1 hit.
PROSITEPS00180. GLNA_1. 1 hit.
PS00181. GLNA_ATP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGLUL. human.
EvolutionaryTraceP15104.
GenomeRNAi2752.
NextBio10840.
PROP15104.
SOURCESearch...

Entry information

Entry nameGLNA_HUMAN
AccessionPrimary (citable) accession number: P15104
Secondary accession number(s): Q499Y9 expand/collapse secondary AC list , Q5T9Z1, Q7Z3W4, Q8IZ17
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 157 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM