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

Summary

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 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; metanephros; and sensory organ. 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, Nov 2024]
Expression: Ubiquitous expression in liver adult (RPKM 50.5), kidney adult (RPKM 34.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

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_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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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?

Prevention of age-related truncation of gamma-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.
Title: Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Variation

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Alleles

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

Endonuclease-mediated (2)
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH124736 (e-PCR)
- UniSTS:161558

Gclc (e-PCR), detects polymorphism
- UniSTS:526898

Gclc (e-PCR), detects polymorphism
- UniSTS:143216

Gclc (e-PCR), detects polymorphism
- UniSTS:545937

Gclc (e-PCR), detects polymorphism
- UniSTS:461976

Gclc (e-PCR), detects polymorphism
- UniSTS:256937

NoName (e-PCR)
- UniSTS:224467

D9Wsu168e (e-PCR), detects polymorphism
- UniSTS:142817

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ADP binding	ISO Inferred from Sequence Orthology more info
enables ADP binding	ISS Inferred from Sequence or Structural Similarity more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables glutamate binding	ISO Inferred from Sequence Orthology more info
enables glutamate binding	ISS Inferred from Sequence or Structural Similarity 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 glutamate-cysteine ligase activity	ISS Inferred from Sequence or Structural Similarity more info
enables magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
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 blood vessel diameter maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell redox homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cell redox homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to fibroblast growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to follicle-stimulating hormone stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hepatocyte growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to thyroxine stimulus	IEA Inferred from Electronic Annotation more info
involved_in cysteine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in cysteine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in glutamate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in glutamate metabolic process	ISS Inferred from Sequence or Structural Similarity 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
involved_in glutathione biosynthetic process	IEA Inferred from Electronic Annotation more info
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
involved_in glutathione biosynthetic process	ISS Inferred from Sequence or Structural Similarity 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 DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
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
involved_in response to activity	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to arsenic-containing substance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in response to heat	ISO Inferred from Sequence Orthology more info
involved_in response to heat	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to hormone	ISO Inferred from Sequence Orthology more info
involved_in response to hormone	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to human chorionic gonadotropin	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-1	IEA Inferred from Electronic Annotation more info
involved_in response to nitrosative stress	IEA Inferred from Electronic Annotation more info
involved_in response to nitrosative stress	ISO Inferred from Sequence Orthology more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in response to oxidative stress	ISS Inferred from Sequence or Structural Similarity 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
located_in mitochondrion	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: glutamate--cysteine ligase catalytic subunit

Names: GCS heavy chain; gamma GCS-HS; gamma-ECS; gamma-glutamylcysteine synthetase heavy subunit

NP_034425.1

EC 6.3.2.2

XP_006510875.1

EC 6.3.2.2

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_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

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

NC_000075.7 Reference GRCm39 C57BL/6J

Range

77661817..77701771

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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