GCLC

Glutamate–cysteine ligase catalytic subunit is an enzyme that in humans is encoded by the GCLC gene.

GCLC
Identifiers
Aliases	GCLC, GCL, GCS, GLCL, GLCLC, glutamate-cysteine ligase catalytic subunit
External IDs	OMIM: 606857; MGI: 104990; HomoloGene: 1148; GeneCards: GCLC; OMA:GCLC - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6p12.1 Start 53,497,341 bp End 53,616,970 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 E1|9 43.36 cM Start 77,661,817 bp End 77,701,767 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bronchial epithelial cell right uterine tube olfactory zone of nasal mucosa gingival epithelium liver nasal epithelium islet of Langerhans epithelium of colon jejunal mucosa right lobe of liver Top expressed in epithelium of stomach left lobe of liver right lung lobe right kidney seminal vesicula human kidney epithelium of lens transitional epithelium of urinary bladder stroma of bone marrow proximal tubule 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 ageing 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: 77.66 – 77.7 Mb PubMed search
Wikidata
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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.

Further reading

• Dickinson DA, Levonen AL, Moellering DR, Arnold EK, Zhang H, Darley-Usmar VM, Forman HJ (Oct 2004). "Human glutamate cysteine ligase gene regulation through the electrophile response element". Free Radical Biology & Medicine. 37 (8): 1152–9. doi:10.1016/j.freeradbiomed.2004.06.011. PMID 15451055.
• Lebo RV, Kredich NM (Apr 1978). "Inactivation of human gamma-glutamylcysteine synthetase by cystamine. Demonstration and quantification of enzyme-ligand complexes". The Journal of Biological Chemistry. 253 (8): 2615–23. doi:10.1016/S0021-9258(17)40865-9. PMID 24639.
• Beutler E, Moroose R, Kramer L, Gelbart T, Forman L (Jan 1990). "Gamma-glutamylcysteine synthetase deficiency and hemolytic anemia". Blood. 75 (1): 271–3. doi:10.1182/blood.V75.1.271.271. PMID 2294991.
• Konrad PN, Richards F, Valentine WN, Paglia DE (Mar 1972). "-Glutamyl-cysteine synthetase deficiency. A cause of hereditary hemolytic anemia". The New England Journal of Medicine. 286 (11): 557–61. doi:10.1056/NEJM197203162861101. PMID 5058793.
• Mulcahy RT, Gipp JJ (Apr 1995). "Identification of a putative antioxidant response element in the 5'-flanking region of the human gamma-glutamylcysteine synthetase heavy subunit gene". Biochemical and Biophysical Research Communications. 209 (1): 227–33. doi:10.1006/bbrc.1995.1493. PMID 7726839.
• Sierra-Rivera E, Summar ML, Dasouki M, Krishnamani MR, Phillips JA, Freeman ML (1995). "Assignment of the gene (GLCLC) that encodes the heavy subunit of gamma-glutamylcysteine synthetase to human chromosome 6". Cytogenetics and Cell Genetics. 70 (3–4): 278–9. doi:10.1159/000134051. PMID 7789189.
• Kondo T, Yoshida K, Urata Y, Goto S, Gasa S, Taniguchi N (Sep 1993). "gamma-Glutamylcysteine synthetase and active transport of glutathione S-conjugate are responsive to heat shock in K562 erythroid cells". The Journal of Biological Chemistry. 268 (27): 20366–72. doi:10.1016/S0021-9258(20)80737-6. PMID 8104187.
• Tsuchiya K, Mulcahy RT, Reid LL, Disteche CM, Kavanagh TJ (Dec 1995). "Mapping of the glutamate-cysteine ligase catalytic subunit gene (GLCLC) to human chromosome 6p12 and mouse chromosome 9D-E and of the regulatory subunit gene (GLCLR) to human chromosome 1p21-p22 and mouse chromosome 3H1-3". Genomics. 30 (3): 630–2. doi:10.1006/geno.1995.1293. PMID 8825659.
• Walsh AC, Li W, Rosen DR, Lawrence DA (1997). "Genetic mapping of GLCLC, the human gene encoding the catalytic subunit of gamma-glutamyl-cysteine synthetase, to chromosome band 6p12 and characterization of a polymorphic trinucleotide repeat within its 5' untranslated region". Cytogenetics and Cell Genetics. 75 (1): 14–6. doi:10.1159/000134447. PMID 8995480.
• Misra I, Griffith OW (Jul 1998). "Expression and purification of human gamma-glutamylcysteine synthetase". Protein Expression and Purification. 13 (2): 268–76. doi:10.1006/prep.1998.0897. PMID 9675072.
• Tu Z, Anders MW (Dec 1998). "Identification of an important cysteine residue in human glutamate-cysteine ligase catalytic subunit by site-directed mutagenesis". The Biochemical Journal. 336 ( Pt 3) (3): 675–80. doi:10.1042/bj3360675. PMC 1219919. PMID 9841880.
• Galloway DC, Blake DG, McLellan LI (Jul 1999). "Regulation of gamma-glutamylcysteine synthetase regulatory subunit (GLCLR) gene expression: identification of the major transcriptional start site in HT29 cells". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1446 (1–2): 47–56. doi:10.1016/S0167-4781(99)00073-1. PMID 10395918.
• Manna SK, Kuo MT, Aggarwal BB (Jul 1999). "Overexpression of gamma-glutamylcysteine synthetase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1". Oncogene. 18 (30): 4371–82. doi:10.1038/sj.onc.1202811. PMID 10439045.
• Beutler E, Gelbart T, Kondo T, Matsunaga AT (Oct 1999). "The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency". Blood. 94 (8): 2890–4. doi:10.1182/blood.V94.8.2890.420k16_2890_2894. PMID 10515893. S2CID 83395002.
• Ristoff E, Augustson C, Geissler J, de Rijk T, Carlsson K, Luo JL, Andersson K, Weening RS, van Zwieten R, Larsson A, Roos D (Apr 2000). "A missense mutation in the heavy subunit of gamma-glutamylcysteine synthetase gene causes hemolytic anemia". Blood. 95 (7): 2193–6. PMID 10733484.
• Tatebe S, Sinicrope FA, Kuo MT (Feb 2002). "Induction of multidrug resistance proteins MRP1 and MRP3 and gamma-glutamylcysteine synthetase gene expression by nonsteroidal anti-inflammatory drugs in human colon cancer cells". Biochemical and Biophysical Research Communications. 290 (5): 1427–33. doi:10.1006/bbrc.2002.6367. PMID 11820781.
• Yang P, Yokomizo A, Tazelaar HD, Marks RS, Lesnick TG, Miller DL, Sloan JA, Edell ES, Meyer RL, Jett J, Liu W (Mar 2002). "Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes". Lung Cancer. 35 (3): 221–9. doi:10.1016/S0169-5002(01)00426-3. PMID 11844594.
• Ray S, Watkins DN, Misso NL, Thompson PJ (Apr 2002). "Oxidant stress induces gamma-glutamylcysteine synthetase and glutathione synthesis in human bronchial epithelial NCI-H292 cells". Clinical and Experimental Allergy. 32 (4): 571–7. doi:10.1046/j.0954-7894.2002.01294.x. PMID 11972604. S2CID 40176433.