P15104 (GLNA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	373 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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
Involvement in disease	Defects in GLUL are the cause of congenital systemic glutamine deficiency (CSGD) [MIM:610015]. CSGD is a 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. Ref.12
Sequence similarities	Belongs to the glutamine synthetase family.

Ontologies

Keywords
Cellular component	Cytoplasm Mitochondrion
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase Lyase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Inferred from direct assay Ref.9. Source: UniProtKB glutamine biosynthetic process Inferred from electronic annotation. Source: InterPro neurotransmitter uptake Traceable author statement. Source: Reactome
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW glutamate decarboxylase activity Inferred from electronic annotation. Source: EC glutamate-ammonia ligase activity Inferred from experiment. Source: Reactome identical protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-746653,EBI-746653

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 373

372

Glutamine synthetase

PRO_0000153139

Amino acid modifications

Modified residue

2

1

N-acetylthreonine By similarity

Modified residue

104

1

Phosphotyrosine By similarity

Modified residue

180

1

Phosphotyrosine By similarity

Natural variations

Natural variant

324

1

R → C in CSGD; reduced glutamine synthetase activity. Ref.12

VAR_026560

Natural variant

341

1

R → C in CSGD; suggests reduced glutamine synthetase activity. Ref.12

VAR_026561

Experimental info

Sequence conflict

7

1

S → Y in AAH31964. Ref.7

Sequence conflict

154

1

F → L in CAD97626. Ref.5

Sequence conflict

155

1

P → T in AAH31964. Ref.7

Sequence conflict

314

1

A → G in CAA68457. Ref.1

Sequence conflict

322 – 323

2

SI → RL in CAA42495. Ref.2

Sequence conflict

347

1

D → E in CAA42495. Ref.2

Secondary structure

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373

Helix Strand Turn

Details...

Helix

5 – 8

4

Helix

11 – 18

8

Beta strand

26 – 33

8

Beta strand

40 – 49

10

Helix

54 – 56

3

Beta strand

60 – 63

4

Turn

64 – 68

5

Beta strand

69 – 71

3

Beta strand

76 – 86

11

Turn

88 – 90

3

Beta strand

95 – 102

8

Helix

114 – 123

10

Helix

124 – 127

4

Beta strand

130 – 140

11

Beta strand

158 – 160

3

Turn

167 – 169

3

Helix

173 – 186

14

Beta strand

190 – 195

6

Beta strand

201 – 210

10

Helix

213 – 232

20

Beta strand

235 – 237

3

Beta strand

245 – 247

3

Beta strand

251 – 257

7

Helix

259 – 262

4

Turn

264 – 266

3

Helix

267 – 278

12

Helix

281 – 287

7

Turn

290 – 295

6

Helix

296 – 298

3

Beta strand

314 – 316

3

Beta strand

321 – 325

5

Helix

327 – 332

6

Beta strand

337 – 339

3

Helix

348 – 359

12

Sequences

	Sequence		Length	Mass (Da)
	P15104 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 45390C100924FAF3	FASTA	373	42,064
	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

References

	« Hide 'large scale' referencesShow '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: 2888076] [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: 1681907] [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: 7909780] [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: 17974005] [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. , 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: 16710414] [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: 15489334] [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. Biokhimiia 67:1012-1020(2002) [PubMed: 12387715] [Abstract] Cited for: MASS SPECTROMETRY, SUBUNIT. 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: 18662667] [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: 18555765] [Abstract] Cited for: INDUCTION.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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: 16267323] [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.

IPI

IPI00010130.

PIR

AJHUQ. S18455.

RefSeq

NP_001028216.1. NM_001033044.2.
NP_001028228.1. NM_001033056.2.
NP_002056.2. NM_002065.5.

UniGene

Hs.518525.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2OJW	X-ray	2.05	A/B/C/D/E	5-364	[»]
2QC8	X-ray	2.60	A/B/C/D/E/F/G/H/I/J	5-365	[»]

ProteinModelPortal

P15104.

SMR

P15104. Positions 10-365.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-308N.

IntAct

P15104. 19 interactions.

MINT

MINT-1183856.

STRING

P15104.

PTM databases

PhosphoSite

P15104.

Polymorphism databases

DMDM

1169929.

2D gel databases

REPRODUCTION-2DPAGE

IPI00010130.

UCD-2DPAGE

P15104.

Proteomic databases

PeptideAtlas

P15104.

PRIDE

P15104.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000311223; ENSP00000307900; ENSG00000135821.
ENST00000331872; ENSP00000356537; ENSG00000135821.
ENST00000339526; ENSP00000344958; ENSG00000135821.
ENST00000417584; ENSP00000398320; ENSG00000135821.

GeneID

2752.

KEGG

hsa:2752.

UCSC

uc001gpa.1. human.

Organism-specific databases

CTD

2752.

GeneCards

GC01M182350.

H-InvDB

HIX0001400.

HGNC

HGNC:4341. GLUL.

HPA

CAB008636.
HPA007316.
HPA007571.

MIM

138290. gene.
610015. phenotype.

neXtProt

NX_P15104.

Orphanet

71278. Congenital brain dysgenesis due to glutamine synthetase deficiency.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG299709.

HOVERGEN

HBG005847.

InParanoid

P15104.

OMA

RLSKRHQ.

OrthoDB

EOG444KKD.

PhylomeDB

P15104.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-13155.

Reactome

REACT_111217. Metabolism.
REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

P15104.

Bgee

P15104.

CleanEx

HS_GLUL.

Genevestigator

P15104.

GermOnline

ENSG00000135821. Homo sapiens.

Family and domain databases

InterPro

IPR008147. Gln_synt_beta.
IPR014746. Gln_synth/guanido_kin_cat_dom.
IPR008146. Gln_synth_cat_dom.
[Graphical view]

Gene3D

G3DSA:3.30.590.10. ATP-gua_Ptrans. 1 hit.
G3DSA:3.10.20.70. G3DSA:3.10.20.70. 1 hit.

KO

K01915.

Pfam

PF00120. Gln-synt_C. 1 hit.
PF03951. Gln-synt_N. 1 hit.
[Graphical view]

SUPFAM

SSF54368. Gln_synt_beta. 1 hit.

PROSITE

PS00180. GLNA_1. 1 hit.
PS00181. GLNA_ATP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00023. Asparaginase.
DB00142. L-Glutamic Acid.
DB00130. L-Glutamine.
DB00134. L-Methionine.

NextBio

10840.

SOURCE

Search...

Entry information

Entry name

GLNA_HUMAN

Accession

Primary (citable) accession number: P15104
Secondary accession number(s): Q499Y9 , Q5T9Z1, Q7Z3W4, Q8IZ17

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 136 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.