Glutamine synthetase (GLUL)

The protein contains 373 amino acids for an estimated molecular weight of 42064 Da.

 

Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:30158707, PubMed:16267323). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351). (updated: May 8, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 21

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VariantDescription
CSGD
CSGD

The reference OMIM entry for this protein is 138290

Glutamate-ammonia ligase; glul
Glutamine synthetase; glns glutamate-ammonia ligase-like 1, included; glull1, included
Glutamate-ammonia ligase-like 2, included; glull2, included
Glutamate-ammonia ligase-like 3, included; glull3, included

DESCRIPTION

Glutamine is a main source of energy and is involved in cell proliferation, inhibition of apoptosis, and cell signaling (Haberle et al., 2005). Fetal glutamine requirements are very high and depend largely on active glutamine synthesis and the release of glutamine into the fetal circulation by the placenta. Glutamine synthetase (EC 6.3.1.2), also called glutamate-ammonia ligase (GLUL), is expressed throughout the body and plays an important role in controlling body pH and in removing ammonia from the circulation. The enzyme clears L-glutamate, the major neurotransmitter in the central nervous system, from neuronal synapses (see references in Clancy et al., 1996).

CLONING

Gibbs et al. (1987) reported the complete 1,119-bp coding sequence of glutamine synthetase, which they determined from a liver-derived cDNA. Haberle et al. (2005) found that the glutamine synthetase mRNA consists of 1,122 basepairs encoding a 374-amino acid protein with an estimated molecular mass of 42 kD.

GENE STRUCTURE

Haberle et al. (2005) determined that the GLUL gene consists of 6 exons.

GENE FUNCTION

Pesole et al. (1991) suggested that glutamine synthetase is a good molecular clock for determining times of divergence even as great as that which occurred between eukaryotes and prokaryotes. One conclusion reached by Pesole et al. (1991) was that organelle-specific enzymes, such as those of the mitochondria, may have originated from a duplication of nuclear genes. The endosymbiotic hypothesis suggests that a transfer of prokaryotic genes to nuclei occurred during the evolution of the primitive eukaryotic cell. In some cases, it is likely that the old prokaryotic gene could not be active in the new nuclear genome environment and was totally lost because its function in the organelle could be dispensed with. Subsequently, a new organelle-specific enzyme could have originated to serve specialized metabolic functions. The presence of glutamine synthetase in mitochondria is linked to the nitrogen metabolism of the species, and in particular to the need for glutamine as a source of ammonia and for particular biochemical pathways for ammonia detoxification. Gunnersen and Haley (1992) found that the 42-kD ATP-binding protein present in the cerebrospinal fluid of Alzheimer disease (AD) patients is glutamine synthetase. It was detected in 38 of 39 AD CSF samples and in only 1 of 44 control samples. In brain, glutamine synthetase plays a key role in elimination of free ammonia and also converts the neurotransmitter and excitotoxic amino acid glutamate to glutamine, which is not neurotoxic.

MAPPING

Clancy et al. (1996) localized the GLUL gene to chromosome 1 by PCR analysis of a human/rodent somatic cell hybrid panel. They also localized a pseudogene to chromosome 9. Further localization of the functional gene to 1q23 was accomplished by fluorescence in situ hybridization. The glutamine synthetase gene was mapped to 5 CEPH mega-YACs between the polymorphic PCR markers D1S117 and D1S466 by analysis of the Whitehead Institute chromosome 1 contig map. By fluorescence in situ hybridization, Helou et al. (1997) placed the GLUL gene at 1q31. Wang et al. (1996) screened a bacterial artificial chromosome (BAC) library with a GLUL probe and isolated 18 clones. Southern blotting of human genomic DNA revealed that all bands could be accounted for by 5 loci, suggesting that humans have a family of 5 glutamine synthetase gen ... More on the omim web site

Subscribe to this protein entry history

May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 138290 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed