GenAge entry for GCLC (Homo sapiens)

Gene name (HAGRID: 237)

HGNC symbol: GCLC
Aliases: GCS; GLCLC; GLCL
Common name: glutamate-cysteine ligase, catalytic subunit

Potential relevance to the human ageing process

Main reason for selection: Entry selected based on evidence linking the gene product to a pathway or mechanism linked to ageing
Description: Glutamate-cysteine ligase, composed of GCLC and GCLM, catalyses the first step in glutathione synthesis. Overexpression of GCLC in fruit flies extended their mean lifespan by 24% [1551]. In humans, mutations in GCLC have been related to hemolytic anemia [1553] and susceptibility to myocardial infarction [1554].

Cytogenetic information

Cytogenetic band: 6p12
Location: 53,497,341 bp to 53,545,129 bp
Orientation: Minus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0000096; sulfur amino acid metabolic process
GO:0006534; cysteine metabolic process
GO:0006536; glutamate metabolic process
GO:0006750; glutathione biosynthetic process
GO:0006979; response to oxidative stress
GO:0007568; aging
GO:0007584; response to nutrient
GO:0008637; apoptotic mitochondrial changes
GO:0009408; response to heat
GO:0009410; response to xenobiotic stimulus
GO:0009725; response to hormone

And 25 more GO terms

Cellular component:

GO:0005829; cytosol
GO:0017109; glutamate-cysteine ligase complex

Function:

GO:0000287; magnesium ion binding
GO:0004357; glutamate-cysteine ligase activity
GO:0005524; ATP binding
GO:0016595; glutamate binding
GO:0043531; ADP binding
GO:0046982; protein heterodimerization activity
GO:0050662; coenzyme binding

Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: GCLM
STRING interaction network

Retrieve sequences for GCLC

ORF: ORF
CDS: CDS

Homologs in model organisms

Caenorhabditis elegans: gcs-1
Danio rerio: gclc
Drosophila melanogaster: Gclc
Mus musculus: Gclc
Rattus norvegicus: Gclc
Saccharomyces cerevisiae: GSH1
Schizosaccharomyces pombe: gcs1

In other databases

GenAge model organism genes

A homolog of this gene for Drosophila melanogaster is present as Gclc

GenDR gene manipulations

A homolog of this gene for Saccharomyces cerevisiae is present as GSH1

LongevityMap

This gene is present as GCLC

Selected references

[1551] Orr et al. (2005) "Overexpression of glutamate-cysteine ligase extends life span in Drosophila melanogaster." J. Biol. Chem. 280(45):37331-37338 (PubMed)
[1289] Brown-Borg and Rakoczy (2005) "Glutathione metabolism in long-living Ames dwarf mice." Exp. Gerontol. 40(1-2):115-120 (PubMed)
[1554] Koide et al. (2003) "Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction." J. Am. Coll. Cardiol. 41(4):539-545 (PubMed)
[1557] Dalton et al. (2000) "Knockout of the mouse glutamate cysteine ligase catalytic subunit (Gclc) gene: embryonic lethal when homozygous, and proposed model for moderate glutathione deficiency when heterozygous." Biochem. Biophys. Res. Commun. 279(2):324-329 (PubMed)
[1552] Liu and Choi (2000) "Age-associated decline in gamma-glutamylcysteine synthetase gene expression in rats." Free Radic. Biol. Med. 28(4):566-574 (PubMed)
[1553] Beutler et al. (1999) "The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency." Blood 94(8):2890-2894 (PubMed)
[1246] Keogh et al. (1996) "Expression of hydrogen peroxide and glutathione metabolizing enzymes in human skin fibroblasts derived from donors of different ages." J. Cell. Physiol. 167(3):512-522 (PubMed)