Tchem GLUL Glutamine synthetase

Protein Summary

Description

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). The protein encoded by this gene belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. This protein plays a role in ammonia and glutamate detoxification, acid-base homeostasis, cell signaling, and cell proliferation. Glutamine is an abundant amino acid, and is important to the biosynthesis of several amino acids, pyrimidines, and purines. Mutations in this gene are associated with congenital glutamine deficiency, and overexpression of this gene was observed in some primary liver cancer samples. There are six pseudogenes of this gene found on chromosomes 2, 5, 9, 11, and 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Uniprot Accession IDs

• P15104
• Q499Y9
• Q5T9Z1
• Q7Z3W4
• Q8IZ17
• GS

Gene Name

• GLUL

Ensembl ID

• ENST00000311223
• ENSP00000307900
• ENSG00000135821
• ENST00000331872
• ENSP00000356537
• ENST00000339526
• ENSP00000344958
• ENST00000417584
• ENSP00000398320

Symbol

• GLNS
• GS
• GLNS
• PIG43
• PIG59

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
molecular function	1
disease perturbation	0.99
transcription factor perturbation	0.97
PubMedID	0.95

Protein Classes

PANTHER Classes

Protein / Ligase / Glutamine Synthetase

DTO Classes

Protein / Enzyme / Ligase / Glutamine Synthetase

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 965.17   (req: < 5)

Gene RIFs: 47   (req: <= 3)

Antibodies: 590   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 965.17   (req: >= 5)

Gene RIFs: 47   (req: > 3)

Antibodies: 590   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 21

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 8

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (2)

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1 – 2 of 2

prednisolone

GLULTchem Enzyme

AGONIST pEC50 : 7.8

prednisolone tebutate

GLULTchem Enzyme

AGONIST pIC50 : 9.28

Active Ligands (8)

Explore Active Ligands

1 – 8 of 8

CHEMBL310570

GLULTchem Enzyme

pKi : 9.1

CHEMBL312399

GLULTchem Enzyme

pIC50 : 8.82

CHEMBL312041

GLULTchem Enzyme

pIC50 : 8.72

CHEMBL311662

GLULTchem Enzyme

pKi : 8.6

CHEMBL82546

GLULTchem Enzyme

pIC50 : 8.55

CHEMBL309243

GLULTchem Enzyme

pIC50 : 8.41

CHEMBL83110

GLULTchem Enzyme

pIC50 : 8.17

CHEMBL3142429

GLULTchem Enzyme

pKi : 6.07

Protein-Protein Interactions (247)

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1 – 10 of 247

• See Interactions on String-DB

TCHP

Tbio

Novelty:  0.00053696

p_int:  0.999999653

p_ni:  2e-9

p_wrong:  3.44e-7

Score:  0.541

Data Source:  BioPlex,STRINGDB

NME7

Tbio

Family:  Enzyme

Novelty:  0.08546782

p_int:  0.999907066

p_ni:  0.000092922

p_wrong:  1.1e-8

Score:  0.308

Data Source:  BioPlex,STRINGDB

ASPSCR1

Tbio

Novelty:  0.01172319

p_int:  0.997579272

p_ni:  0.002420727

Score:  0.497

Data Source:  BioPlex,STRINGDB

DMXL2

Tbio

Novelty:  0.06848356

p_int:  0.99102745

p_ni:  0.008972295

p_wrong:  2.54e-7

Score:  0.211

Data Source:  BioPlex,STRINGDB

ZFAND2B

Tbio

Novelty:  0.28286118

p_int:  0.940934685

p_ni:  0.059065315

Score:  0.19

Data Source:  BioPlex,STRINGDB

C1orf94

Tdark

Novelty:  23

p_int:  0.838068305

p_ni:  0.161931695

Score:  0.187

Data Source:  BioPlex,STRINGDB

LNP1

Tdark

Novelty:  0.00457285

p_int:  0.823130896

p_ni:  0.176869104

Data Source:  BioPlex

TBC1D22B

Tbio

Novelty:  0.49852962

p_int:  0.765637

p_ni:  0.234363

Data Source:  BioPlex

RNASEH2C

Tbio

Family:  Enzyme

Novelty:  0.06148299

p_int:  0.751941926

p_ni:  0.248058074

Data Source:  BioPlex

GLUD1

Tbio

Family:  Enzyme

Novelty:  0.00301109

Score:  0.983

Data Source:  STRINGDB

Nearest Tclin Targets (3)

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Upstream (2)

Downstream (1)

1 – 2 of 2

CPS1

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  5

1: Alanine, aspartate and glutamate metabolism

2: Metabolic pathways

3: Nitrogen metabolism

4: Biosynthesis of amino acids

5: Arginine biosynthesis

PPAT

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  2

1: Alanine, aspartate and glutamate metabolism

2: Metabolic pathways

Pathways (27)

Reactome (7)

KEGG (9)

PathwayCommons (5)

WikiPathways (6)

Astrocytic Glutamate-Glutamine Uptake And Metabolism (R-HSA-210455)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Astrocytic Glutamate-Glutamine Uptake And Metabolism	4 targets	R-HSA-210455
Reactome	Glutamate and glutamine metabolism	13 targets	R-HSA-8964539
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Reactome	Neuronal System	398 targets	R-HSA-112316

Name	Explore in Pharos	Explore in Source
Astrocytic Glutamate-Glutamine Uptake And Metabolism	4 targets	R-HSA-210455
Glutamate and glutamine metabolism	13 targets	R-HSA-8964539
Metabolism	2112 targets	R-HSA-1430728
Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Neuronal System	398 targets	R-HSA-112316

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (32)

Functions (8)

Components (11)

Processes (13)

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10

1 – 8 of 8

GO Term	Evidence	Assigned by
glutamate-ammonia ligase activity	Inferred from Experiment (EXP)	Reactome
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
dynein light chain binding	Inferred from Electronic Annotation (IEA)	Ensembl
glutamate binding	Inferred from Electronic Annotation (IEA)	Ensembl
magnesium ion binding	Inferred from Electronic Annotation (IEA)	Ensembl
manganese ion binding	Inferred from Electronic Annotation (IEA)	Ensembl
protein-cysteine S-palmitoyltransferase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-EC

Disease Associations ()

No disease associations found

GWAS Traits (4)

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1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
chronotype measurement	EFO_0008328	1	2	0	1.3	83.5
electrocardiography	EFO_0004327	1	1	44		12.9
red blood cell distribution width	EFO_0005192	1	1	1		9.9
high density lipoprotein cholesterol measurement	EFO_0004612	1	1	1		2

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
chronotype measurement	EFO_0008328	0	1.3	83.5
electrocardiography	EFO_0004327	44		12.9
red blood cell distribution width	EFO_0005192	1		9.9
high density lipoprotein cholesterol measurement	EFO_0004612	1		2

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Angiogenesis
ATP-binding
Cell membrane
Complete proteome
Cytoplasm
Disease mutation
Endoplasmic reticulum
Ligase

GWAS Trait Find Similar Targets

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chronotype measurement
electrocardiography
high density lipoprotein cholesterol measurement
red blood cell distribution width

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
mortality/aging
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	glutamate-ammonia ligase	VGNC:11441	456450
Macaque	glutamate-ammonia ligase		715952
Mouse	glutamate-ammonia ligase (glutamine synthetase)	MGI:95739	14645
Rat	glutamate-ammonia ligase	RGD:2710	24957
Dog	glutamate-ammonia ligase		403443

Species	Name	OMA	EggNOG	Inparanoid
Chimp	glutamate-ammonia ligase
Macaque	glutamate-ammonia ligase
Mouse	glutamate-ammonia ligase (glutamine synthetase)
Rat	glutamate-ammonia ligase
Dog	glutamate-ammonia ligase

Publication Statistics

PubMed Score 965.17

PubMed score by year

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PubTator Score 1793.10

PubTator score by year

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Related Publications

GeneRif Annotations (47)

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PMID	Text