GCLC

GCLC
Identifiers
Aliases	GCLC, GCL, GCS, GLCL, GLCLC, glutamate-cysteine ligase catalytic subunit
External IDs	OMIM: 606857 MGI: 104990 HomoloGene: 1148 GeneCards: GCLC
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p12.1 Start 53,497,341 bp[1] End 53,616,970 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 E1|9 43.36 cM Start 77,754,535 bp[2] End 77,794,485 bp[2]
RNA expression pattern Bgee Top expressed in ovary corpus callosum urinary bladder liver lung endometrium substantia nigra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding ADP binding ligase activity glutamate-cysteine ligase activity protein heterodimerization activity ATP binding magnesium ion binding glutamate binding catalytic activity Cellular component cytosol glutamate-cysteine ligase complex Biological process negative regulation of neuron apoptotic process response to drug glutathione metabolic process cysteine metabolic process negative regulation of extrinsic apoptotic signaling pathway response to heat negative regulation of apoptotic process response to arsenic-containing substance response to oxidative stress cell redox homeostasis regulation of mitochondrial depolarization negative regulation of protein ubiquitination apoptotic mitochondrial changes response to nitrosative stress response to hormone glutamate metabolic process negative regulation of transcription, DNA-templated positive regulation of proteasomal ubiquitin-dependent protein catabolic process L-ascorbic acid metabolic process cellular response to insulin stimulus aging negative regulation of hepatic stellate cell activation cellular response to thyroxine stimulus cellular response to follicle-stimulating hormone stimulus cellular response to fibroblast growth factor stimulus response to human chorionic gonadotropin response to interleukin-1 cellular response to mechanical stimulus response to nutrient response to activity response to cadmium ion cellular response to hepatocyte growth factor stimulus cellular response to glucose stimulus glutathione biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2729	14629
Ensembl	ENSG00000001084	ENSMUSG00000032350
UniProt	P48506	P97494
RefSeq (mRNA)	NM_001498 NM_001197115	NM_010295
RefSeq (protein)	NP_001184044 NP_001489	NP_034425
Location (UCSC)	Chr 6: 53.5 – 53.62 Mb	Chr 9: 77.75 – 77.79 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Glutamate—cysteine ligase catalytic subunit is an enzyme that in humans is encoded by the GCLC gene.^[5][6]

Function[]

Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. The gene encoding the catalytic subunit encodes a protein of 367 amino acids with a calculated molecular weight of 72.773 kDa and maps to chromosome 6. The regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Deficiency of gamma-glutamylcysteine synthetase in human is associated with enzymopathic hemolytic anemia.^[6]

Model organisms[]

Model organisms have been used in the study of GCLC function. A conditional knockout mouse line, called Gclc^{tm1a(EUCOMM)Wtsi[11][12]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.^[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[9][16] Twenty four tests were carried out on mutant mice, however no significant abnormalities were observed.^[9]

References[]

Further reading[]