|Gene:||GLUL||Accession Number: G-10005 (MetaCyc)|
Species: Homo sapiens
Subunit composition of
glutamine synthetase, type II = [GLUL]8
glutamine synthetase subunit = GLUL
The relative molecular mass of native glutamine synthetase purified from human brain was estimated to be 360-400 kD as determined by native gel electrophoresis, suggesting an octameric subunit structure [Tumani95].
Glutamine synthetase is a key enzyme of nitrogen metabolism found in all domains of life. Phylogenetic analysis of glutamine synthetase genes has suggested that they are among the oldest functioning genes in the history of evolution [Kumada93]. There are three types of glutamine synthetase, differing in relative molecular mass and number of subunits. Glutamine synthetase type I, found mostly in bacteria and archaea, is a well-studied homododecamer with subunits of 44-60 kD. It is built from two back-to-back hexameric rings. Glutamine synthetase type II is found mostly in eukaryotes and some soil bacteria, but has been also described in a halophilic archaeon [MartinezEspinos06]. It is a homooctamer with subunits of 35-50 kD. Type III glutamine synthetase has been described in anaerobic bacteria and cyanobacteria, and is a homohexamer with subunits of approximately 75 kD. The active site residues of all three types of glutamine synthetase are conserved. In [MartinezEspinos06, Amaya05, Llorca06].
The vertebrate enzyme is the product of a single gene, but mitochondrial and cytosolic isozymes are found, depending upon tissue (in [Shin04a]). In humans, this ubiquitous enzyme if found in high concentrations in liver, brain and muscle. In human liver it is localized to a subpopulation of perivenous parenchymal cells; in brain it is mainly found in the cytoplasm of astrocytes; and in skeletal muscle it is expressed in most cells. Mutations in the gene encoding glutamine synthetase have been identified, and are associated with severely reduced enzyme activity and fatality during the neonatal period (reviewed in [Haberle06]).
The relative molecular mass of the glutamine synthetase subunit purified from human brain was determined by SDS-PAGE. On two-dimensional electrophoresis the subunits showed heterogeneity, with isoelectric points of 7.07, 7.12 and 7.2 [Tumani95].
|Map Position: [180,618,292 <- 180,627,573]|
Molecular Weight of Polypeptide: 42.064 kD (from nucleotide sequence), 44 kD (experimental) [Tumani95 ]
Molecular Weight of Multimer: 360 kD (experimental) [Tumani95]
Unification Links: ArrayExpress:P15104 , DIP:DIP-308N , Entrez-gene:2752 , Mint:MINT-1183856 , PhosphoSite:P15104 , Pride:P15104 , Protein Model Portal:P15104 , SMR:P15104 , String:9606.ENSP00000307900 , UniProt:P15104
Relationship Links: InterPro:IN-FAMILY:IPR008146 , InterPro:IN-FAMILY:IPR008147 , InterPro:IN-FAMILY:IPR014746 , InterPro:IN-FAMILY:IPR027302 , InterPro:IN-FAMILY:IPR027303 , PDB:Structure:2OJW , PDB:Structure:2QC8 , Pfam:IN-FAMILY:PF00120 , Pfam:IN-FAMILY:PF03951 , Prosite:IN-FAMILY:PS00180 , Prosite:IN-FAMILY:PS00181
Enzymatic reaction of: glutamine synthetase
Synonyms: GS, glutamate ammonia ligase
EC Number: 22.214.171.124
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is physiologically favored in the direction shown.
Glutamine synthetase catalyzes the biosynthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. The kinetic constants given here are for purified, recombinant human glutamine synthetase expressed in Escherichia coli [Listrom97].
Amaya05: Amaya KR, Kocherginskaya SA, Mackie RI, Cann IK (2005). "Biochemical and mutational analysis of glutamine synthetase type III from the rumen anaerobe Ruminococcus albus 8." J Bacteriol 187(21);7481-91. PMID: 16237031
Haberle06: Haberle J, Gorg B, Toutain A, Rutsch F, Benoist JF, Gelot A, Suc AL, Koch HG, Schliess F, Haussinger D (2006). "Inborn error of amino acid synthesis: human glutamine synthetase deficiency." J Inherit Metab Dis 29(2-3);352-8. PMID: 16763901
Kumada93: Kumada Y, Benson DR, Hillemann D, Hosted TJ, Rochefort DA, Thompson CJ, Wohlleben W, Tateno Y (1993). "Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes." Proc Natl Acad Sci U S A 90(7);3009-13. PMID: 8096645
Listrom97: Listrom CD, Morizono H, Rajagopal BS, McCann MT, Tuchman M, Allewell NM (1997). "Expression, purification, and characterization of recombinant human glutamine synthetase." Biochem J 328 ( Pt 1);159-63. PMID: 9359847
Llorca06: Llorca O, Betti M, Gonzalez JM, Valencia A, Marquez AJ, Valpuesta JM (2006). "The three-dimensional structure of an eukaryotic glutamine synthetase: functional implications of its oligomeric structure." J Struct Biol 156(3);469-79. PMID: 16884924
MartinezEspinos06: Martinez-Espinosa RM, Esclapez J, Bautista V, Bonete MJ (2006). "An octameric prokaryotic glutamine synthetase from the haloarchaeon Haloferax mediterranei." FEMS Microbiol Lett 264(1);110-6. PMID: 17020556
Tumani95: Tumani H, Shen GQ, Peter JB (1995). "Purification and immunocharacterization of human brain glutamine synthetase and its detection in cerebrospinal fluid and serum by a sandwich enzyme immunoassay." J Immunol Methods 188(1);155-63. PMID: 8551033
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