U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Gclc glutamate-cysteine ligase, catalytic subunit [ Mus musculus (house mouse) ]

Gene ID: 14629, updated on 21-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
Gclcprovided by MGI
Official Full Name
glutamate-cysteine ligase, catalytic subunitprovided by MGI
Primary source
MGI:MGI:104990
See related
Ensembl:ENSMUSG00000032350 AllianceGenome:MGI:104990
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
Glclc; GLCL-H; Ggcs-hs; D9Wsu168e
Summary
Enables glutamate-cysteine ligase activity. Acts upstream of or within several processes, including glutathione biosynthetic process; negative regulation of apoptotic signaling pathway; and regulation of cellular protein metabolic process. Located in cytosol. Part of glutamate-cysteine ligase complex. Is expressed in several structures, including alimentary system; central nervous system; integumental system; sensory organ; and urinary system. Used to study cataract. Human ortholog(s) of this gene implicated in cystic fibrosis; glutamate-cysteine ligase deficiency; hemolytic anemia; and myocardial infarction. Orthologous to human GCLC (glutamate-cysteine ligase catalytic subunit). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in liver adult (RPKM 50.5), kidney adult (RPKM 34.6) and 28 other tissues See more
Orthologs
human all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
9 E1; 9 43.36 cM
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 9 NC_000075.7 (77661817..77701771)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 9 NC_000075.6 (77754535..77794489)

Chromosome 9 - NC_000075.7Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_24700 Neighboring gene chimerin (chimaerin) 1 pseudogene Neighboring gene CapStarr-seq enhancer MGSCv37_chr9:77440338-77440521 Neighboring gene STARR-positive B cell enhancer ABC_E2905 Neighboring gene STARR-seq mESC enhancer starr_24701 Neighboring gene STARR-seq mESC enhancer starr_24702 Neighboring gene STARR-positive B cell enhancer ABC_E6770 Neighboring gene kelch-like 31 Neighboring gene STARR-seq mESC enhancer starr_24703 Neighboring gene STARR-seq mESC enhancer starr_24704 Neighboring gene STARR-positive B cell enhancer ABC_E3846 Neighboring gene STARR-seq mESC enhancer starr_24706 Neighboring gene predicted gene, 34654 Neighboring gene STARR-positive B cell enhancer mm9_chr9:77758381-77758682 Neighboring gene STARR-positive B cell enhancer ABC_E6772 Neighboring gene STARR-positive B cell enhancer ABC_E2906 Neighboring gene CapStarr-seq enhancer MGSCv37_chr9:77766361-77766544 Neighboring gene STARR-positive B cell enhancer mm9_chr9:77778672-77778973 Neighboring gene ELOVL fatty acid elongase 5 Neighboring gene predicted gene, 34771

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Proteomic analysis of the glutathione-deficient LEGSKO mouse lens reveals activation of EMT signaling, loss of lens specific markers, and changes in stress response proteins. Whitson JA, et al. Free Radic Biol Med, 2017 Dec. PMID 28951044, Free PMC Article
  2. Reduced Glutathione Level Promotes Epithelial-Mesenchymal Transition in Lens Epithelial Cells via a Wnt/β-Catenin-Mediated Pathway: Relevance for Cataract Therapy. Wei Z, et al. Am J Pathol, 2017 Nov. PMID 28827139, Free PMC Article
  3. Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis. Whitson JA, et al. Invest Ophthalmol Vis Sci, 2017 May 1. PMID 28525556, Free PMC Article
  4. Glutathione Primes T Cell Metabolism for Inflammation. Mak TW, et al. Immunity, 2017 Apr 18. PMID 28423341
  5. The oxidized thiol proteome in aging and cataractous mouse and human lens revealed by ICAT labeling. Wang B, et al. Aging Cell, 2017 Apr. PMID 28177569, Free PMC Article

See all (88) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Cystine/Glutamate Xc[-] Antiporter Induction Compensates for Transsulfuration Pathway Repression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) to Ensure Cysteine for Hepatic Glutathione Biosynthesis.
    Title: Cystine/Glutamate Xc(-) Antiporter Induction Compensates for Transsulfuration Pathway Repression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) to Ensure Cysteine for Hepatic Glutathione Biosynthesis.
  2. Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells.
    Title: Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells.
  3. Carnosic Acid Attenuates an Early Increase in ROS Levels during Adipocyte Differentiation by Suppressing Translation of Nox4 and Inducing Translation of Antioxidant Enzymes.
    Title: Carnosic Acid Attenuates an Early Increase in ROS Levels during Adipocyte Differentiation by Suppressing Translation of Nox4 and Inducing Translation of Antioxidant Enzymes.
  4. The development of glutamate cysteine ligase [GCL] transgenic and gene deletion mouse lines are described.
    Title: Glutamate cysteine ligase (GCL) transgenic and gene-targeted mice for controlling glutathione synthesis.
  5. The findings indicate that expression of the transcription factor NRF2 and its effector GCL are both profoundly deregulated in endometriotic lesions towards increased growth and fibrogenetic processes.
    Title: Alteration of Nrf2 and Glutamate Cysteine Ligase expression contribute to lesions growth and fibrogenesis in ectopic endometriosis.
  6. Retinal GCLC was significantly increased in rd10 mice at P21 as well as GSSG. Our results suggest alterations in retinal GCLC content and GSH and/or its precursors in these two RP animal models. Regulation of the enzymes related to GSH metabolism and the retinal concentration of glutamate may be a possible target to delay especially cone death in Retinitis Pigmentosa
    Title: Alterations in glutamate cysteine ligase content in the retina of two retinitis pigmentosa animal models.
  7. Data show that the catalytic subunit of glutamate cysteine ligase (Gclc)-derived glutathione buffers reactive oxygen species (ROS), and regulates metabolic reprogramming.
    Title: Glutathione Primes T Cell Metabolism for Inflammation.
  8. To study the biological effects of low GSH levels, we disrupted its synthesis both at birth by breeding a Gclc loxP mouse with a thy1-cre mouse and at a later age by breeding with a CaMKII-ERT2-Cre (FIGSKO mouse). FIGSKO mice also develop cognitive abnormalities, i.e. learning impairment and nesting behaviors based on passive avoidance, T-Maze, and nesting behavior tests
    Title: Gclc deficiency in mouse CNS causes mitochondrial damage and neurodegeneration.
  9. A floxed Gclc mouse was generated and crossed with a transgenic mouse expressing Cre in the lens to generate the Lens Glutathione Synthesis Knockout mouse in which de novo GSH synthesis was completely abolished in the lens.
    Title: The LEGSKO mouse: a mouse model of age-related nuclear cataract based on genetic suppression of lens glutathione synthesis.
  10. Clinically relevant levels of TGF-beta1 suppresses GCLC and GCLM expression in mouse lung.
    Title: Transforming growth factor β suppresses glutamate-cysteine ligase gene expression and induces oxidative stress in a lung fibrosis model.
Submit: New GeneRIF Correction See all GeneRIFs (25)

Variation

Go to the top of the page Help

Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (5)  1 citation
  • Endonuclease-mediated (2) 

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables ADP binding ISO
Inferred from Sequence Orthology
more info
  
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables catalytic activity IEA
Inferred from Electronic Annotation
more info
  
enables glutamate binding ISO
Inferred from Sequence Orthology
more info
  
enables glutamate-cysteine ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables glutamate-cysteine ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables glutamate-cysteine ligase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables glutamate-cysteine ligase activity ISO
Inferred from Sequence Orthology
more info
  
enables ligase activity IEA
Inferred from Electronic Annotation
more info
  
enables magnesium ion binding ISO
Inferred from Sequence Orthology
more info
  
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-containing complex binding ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within L-ascorbic acid metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in blood vessel diameter maintenance ISO
Inferred from Sequence Orthology
more info
  
involved_in cell redox homeostasis ISO
Inferred from Sequence Orthology
more info
  
involved_in cysteine metabolic process ISO
Inferred from Sequence Orthology
more info
  
involved_in glutamate metabolic process ISO
Inferred from Sequence Orthology
more info
  
involved_in glutathione biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within glutathione biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within glutathione biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in glutathione biosynthetic process ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within glutathione metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of DNA-templated transcription ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of apoptotic process ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within negative regulation of extrinsic apoptotic signaling pathway IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in negative regulation of hepatic stellate cell activation ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in negative regulation of neuron apoptotic process ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within negative regulation of protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within positive regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within regulation of mitochondrial depolarization IGI
Inferred from Genetic Interaction
more info
 PubMed 
acts_upstream_of_or_within response to arsenic-containing substance IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in response to heat ISO
Inferred from Sequence Orthology
more info
  
involved_in response to hormone ISO
Inferred from Sequence Orthology
more info
  
involved_in response to nitrosative stress ISO
Inferred from Sequence Orthology
more info
  
involved_in response to oxidative stress ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within response to xenobiotic stimulus IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
part_of glutamate-cysteine ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of glutamate-cysteine ligase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of glutamate-cysteine ligase complex ISO
Inferred from Sequence Orthology
more info
  

General protein information

Go to the top of the page Help
Preferred Names
glutamate--cysteine ligase catalytic subunit
Names
GCS heavy chain
gamma GCS-HS
gamma-ECS
gamma-glutamylcysteine synthetase heavy subunit
NP_034425.1
XP_006510875.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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)

  1. NM_010295.2 → NP_034425.1  glutamate--cysteine ligase catalytic subunit

    See identical proteins and their annotated locations for NP_034425.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the protein-coding transcript.
    Source sequence(s)
    AK144339, AK160876, EH103060
    Consensus CDS
    CCDS23354.1
    UniProtKB/Swiss-Prot
    O09166, P97494, Q8VCS5
    UniProtKB/TrEMBL
    Q3TEF1, Q3UNA7
    Related
    ENSMUSP00000034905.9, ENSMUST00000034905.9
    Conserved Domains (1) summary
    pfam03074
    Location:236 → 608
    GCS; Glutamate-cysteine ligase

RNA

  1. NR_151778.1 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) contains an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC159886, AC160124

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000075.7 Reference GRCm39 C57BL/6J

    Range
    77661817..77701771
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006510812.2 → XP_006510875.1  glutamate--cysteine ligase catalytic subunit isoform X1

    UniProtKB/TrEMBL
    Q3UNA7
    Conserved Domains (1) summary
    pfam03074
    Location:183 → 555
    GCS; Glutamate-cysteine ligase
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P97494.4 GenPept UniProtKB/Swiss-Prot:P97494

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Other Literature Sources
Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous