Glul glutamate-ammonia ligase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Glulprovided by MGI
Official Full Name: glutamate-ammonia ligaseprovided by MGI
Primary source: MGI:MGI:95739
See related: Ensembl:ENSMUSG00000026473 AllianceGenome:MGI:95739
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: GS; Glns
Summary: Predicted to enable several functions, including anion binding activity; dynein light chain binding activity; and metal ion binding activity. Involved in regulation of endothelial cell migration and regulation of sprouting angiogenesis. Acts upstream of or within cellular response to starvation and response to glucose. Located in cell body; cytoplasm; and glial cell projection. Is expressed in several structures, including alimentary system; central nervous system; respiratory system; sensory organ; and urinary system. Used to study temporal lobe epilepsy. Human ortholog(s) of this gene implicated in congenital glutamine deficiency; epilepsy (multiple); heart disease; and neurodegenerative disease (multiple). Orthologous to human GLUL (glutamate-ammonia ligase). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Broad expression in genital fat pad adult (RPKM 555.7), frontal lobe adult (RPKM 388.8) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 G3; 1 65.43 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (153775692..153785469)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (153899929..153909723)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.
Title: Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.
Astrocyte S100beta expression and selective differentiation to GFAP and GS in the entorhinal cortex during ageing in the 3xTg-Alzheimer's disease mouse model.
Title: Astrocyte S100β expression and selective differentiation to GFAP and GS in the entorhinal cortex during ageing in the 3xTg-Alzheimer's disease mouse model.
DNA-Encoded Glutamine Synthetase Enzyme as Ammonia-Lowering Therapeutic for Hyperammonemia.
Title: DNA-Encoded Glutamine Synthetase Enzyme as Ammonia-Lowering Therapeutic for Hyperammonemia.
Gln synthetase (GS) activity and expression significantly increase from postnatal day 7 to 21 in newborn mice and GS is expressed prior to GFAP and is more abundant than GFAP throughout synaptogenesis. Inhibiting GS activity in neonatal mice resulted in spatial memory-related impairment in adults. Results suggest that postnatal GS activity is important for glutamatergic synapse development in CA3.
Title: Insufficient glutamine synthetase activity during synaptogenesis causes spatial memory impairment in adult mice.
genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells
Title: Role of glutamine synthetase in angiogenesis beyond glutamine synthesis.
The data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis.
Title: Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis.
Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention
Title: Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells.
We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.
Title: Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.
Diabetes induces TXNIP expressions at mRNA levels, but shows the opposite effect on GS.
Title: Thioredoxin-Interacting Protein (TXNIP) Suppresses Expression of Glutamine Synthetase by Inducing Oxidative Stress in Retinal Muller Glia Under Diabetic Conditions.
Results indicate that astrocyte glutamine synthase may be the predominant contributor to the pathogenic mechanisms of D-gal-induced brain aging in mice.
Title: Glutamine synthetase plays a role in D-galactose-induced astrocyte aging in vitro and in vivo.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (9) 1 citation
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Glul (e-PCR), detects polymorphism
- UniSTS:545940

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables dynein light chain binding	ISO Inferred from Sequence Orthology more info
enables glutamate binding	ISO Inferred from Sequence Orthology more info
enables glutamine synthetase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutamine synthetase activity	ISO Inferred from Sequence Orthology more info
enables glutamine synthetase activity	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables manganese ion binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nickel cation binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-cysteine S-palmitoyltransferase activity	ISO Inferred from Sequence Orthology more info
enables protein-cysteine S-palmitoyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in ammonia assimilation cycle	ISO Inferred from Sequence Orthology more info
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in cell population proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to starvation	IEP Inferred from Expression Pattern more info	PubMed
involved_in glutamate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in glutamine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutamine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in glutamine biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic transmission, glutamatergic	ISO Inferred from Sequence Orthology more info
involved_in protein palmitoylation	ISO Inferred from Sequence Orthology more info
involved_in protein palmitoylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of endothelial cell migration	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein localization to nucleolus	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein localization to nucleolus	ISO Inferred from Sequence Orthology more info
involved_in regulation of sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of sprouting angiogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to glucose	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ribosome biogenesis	IEA Inferred from Electronic Annotation more info
involved_in ribosome biogenesis	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in axon terminus	ISO Inferred from Sequence Orthology more info
located_in cell body	IDA Inferred from Direct Assay more info	PubMed
located_in cell projection	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in glial cell projection	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in myelin sheath	HDA more info	PubMed
located_in myelin sheath	ISO Inferred from Sequence Orthology more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: glutamine synthetase

Names: glutamate decarboxylase; glutamate-ammonia ligase (glutamine synthase); glutamate-ammonia ligase (glutamine synthetase); palmitoyltransferase GLUL

NP_032157.2

EC 2.3.1.225

EC 6.3.1.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_008131.5 → NP_032157.2 glutamine synthetase

See identical proteins and their annotated locations for NP_032157.2

Status: VALIDATED

Source sequence(s)

AC099702

Consensus CDS

CCDS15381.1

UniProtKB/Swiss-Prot

P15105, Q3TRK7, Q64432, Q91VC6

UniProtKB/TrEMBL

V9GZG5

Related

ENSMUSP00000083375.6, ENSMUST00000086199.12

Conserved Domains (3) summary

PLN02284
Location:22 → 362

PLN02284; glutamine synthetase

pfam00120
Location:114 → 356

Gln-synt_C; Glutamine synthetase, catalytic domain

pfam03951
Location:30 → 104

Gln-synt_N; Glutamine synthetase, beta-Grasp domain