Gclc glutamate-cysteine ligase, catalytic subunit [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Gclcprovided by RGD
Official Full Name: glutamate-cysteine ligase, catalytic subunitprovided by RGD
Primary source: RGD:619868
See related: EnsemblRapid:ENSRNOG00000006302 AllianceGenome:RGD:619868
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Glclc
Summary: Enables glutamate-cysteine ligase activity. Involved in several processes, including cellular response to follicle-stimulating hormone stimulus; cellular response to hepatocyte growth factor stimulus; and cellular response to mechanical stimulus. Part of glutamate-cysteine ligase complex. Used to study liver cirrhosis and pulmonary emphysema. 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, Dec 2024]
Expression: Biased expression in Kidney (RPKM 5694.5), Liver (RPKM 449.6) and 1 other tissue See more
Orthologs: human mouse all
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Genomic context

Location:: 8q31

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	8	NC_086026.1 (87510251..87548896)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	8	NC_051343.1 (78629899..78668547)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	8	NC_005107.4 (85059051..85097471)

Chromosome 8 - NC_086026.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Study determined the effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits (GCLM and GCLC) in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rat: troxerutin alleviates oxidative stress and promotes learning potential in STZ-induced diabetic rats likely through GCL mechanisms, especially that of GCLC.
Title: Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats.
in diabetic retinopathy, histone methylation at Gclc-ARE4 plays an important role in regulating the Nrf2-Gclc-GSH cascade.
Title: Epigenetic modifications of Nrf2-mediated glutamate-cysteine ligase: implications for the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression.
Increased GCLC protein expression in the lungs were observed in the rats exposed to biomass smoke and cigarette smoke.
Title: Development and systematic oxidative stress of a rat model of chronic bronchitis and emphysema induced by biomass smoke.
sumoylation of Nrf2 and MafG enhances heterodimerization and increases GCLC expression, which keeps HSCs in a quiescent state.
Title: Mechanism and significance of changes in glutamate-cysteine ligase expression during hepatic fibrogenesis.
After exposure to 95% oxygen accumulation of nuclear ATF4 protein in whole lung extracts coincided with induction of glutamate-cysteine ligase catalytic subunit, an intregrated stress response gene.
Title: Hyperoxia-induced activation of the integrated stress response in the newborn rat lung.
Data show that activation of the PPARgamma/PGC-1alpha pathway may protect against COPD progression by upregulating gamma-GCS and relieving oxidative stress.
Title: Positive correlation between PPARgamma/PGC-1alpha and gamma-GCS in lungs of rats and patients with chronic obstructive pulmonary disease.
The protection exerted by sulforaphane(SFN) on mitochondrial alterations and NQO1 and gammaGCL enzymes may be involved in the renoprotection of SFN against cisplatin.
Title: Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H: quinone oxidoreductase 1 and γ glutamyl cysteine ligase: studies in mitochondria isolated from rat kidney and in LLC-PK1 cells.
Allitidum may increase the antioxidative ability of CCL-149 cells by increasing the expression of gamma-GCS protein and the content of glutathione.
Title: [Effect of allitridum on expression of the gamma-glutamyl-cysteine synthetase in rat lung epithelial L2 cells].
After a single dose of deltamethrin, GCSh mRNA relative levels in cerebral cortex in rats were significantly decreased.
Title: [Time course of gene expression of gamma-glutamylcysteine synthetase subunit and Nrf2 in brain tissues of rats exposed by deltamethrin].
Aging impairs the expression of the catalytic subunit of glutamate cysteine ligase in soleus muscle under stress.
Title: Aging impairs the expression of the catalytic subunit of glutamate cysteine ligase in soleus muscle under stress.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

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

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

RH128816 (e-PCR)
- UniSTS:212124

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

Gene Ontology Provided by RGD

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	IEA Inferred from Electronic Annotation more info
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-containing complex binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within L-ascorbic acid metabolic process	ISO Inferred from Sequence Orthology more info
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	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to follicle-stimulating hormone stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to glucose stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to hepatocyte growth factor stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to insulin stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to thyroxine stimulus	IEP Inferred from Expression Pattern more info	PubMed
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
involved_in glutathione biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in glutathione biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glutathione biosynthetic process	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of hepatic stellate cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of protein ubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of mitochondrial depolarization	ISO Inferred from Sequence Orthology more info
involved_in response to activity	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within response to arsenic-containing substance	ISO Inferred from Sequence Orthology more info
involved_in response to auditory stimulus	ISO Inferred from Sequence Orthology more info
involved_in response to cadmium ion	IEP Inferred from Expression Pattern more info	PubMed
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	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to interleukin-1	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to nitrosative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to nutrient	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
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	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cytosol	ISO Inferred from Sequence Orthology more info
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; Glutamylcysteine gamma synthetase light chain; gamma-ECS; gamma-glutamylcysteine synthetase

NP_036947.1

EC 6.3.2.2

XP_038936798.1

EC 6.3.2.2

XP_063121015.1

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_012815.2 → NP_036947.1 glutamate--cysteine ligase catalytic subunit

See identical proteins and their annotated locations for NP_036947.1

Status: PROVISIONAL

Source sequence(s)

BC081702

UniProtKB/Swiss-Prot

P19468

UniProtKB/TrEMBL

A0A8I5ZU55, A6I1G6

Related

ENSRNOP00000035540.3, ENSRNOT00000033196.5

Conserved Domains (2) summary

PRK06299
Location:26 → 67

rpsA; 30S ribosomal protein S1; Reviewed

pfam03074
Location:236 → 608

GCS; Glutamate-cysteine ligase

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086026.1 Reference GRCr8

Range

87510251..87548896

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039080870.2 → XP_038936798.1 glutamate--cysteine ligase catalytic subunit isoform X2

Conserved Domains (2) summary

PRK06299
Location:26 → 67

rpsA; 30S ribosomal protein S1; Reviewed

pfam03074
Location:236 → 361

GCS; Glutamate-cysteine ligase
XM_063264945.1 → XP_063121015.1 glutamate--cysteine ligase catalytic subunit isoform X1

UniProtKB/TrEMBL

A0A8I5ZU55