GCLC

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Glutamate-cysteine ligase, catalytic subunit
Identifiers
Symbols GCLC ; GCS; GLCL; GLCLC
External IDs Template:OMIM5 Template:MGI HomoloGene1148
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

Glutamate-cysteine ligase, catalytic subunit, also known as GCLC, is a human gene.[1]

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.[1]

References

  1. 1.0 1.1 "Entrez Gene: GCLC glutamate-cysteine ligase, catalytic subunit".

Further reading

  • Dickinson DA, Levonen AL, Moellering DR; et al. (2005). "Human glutamate cysteine ligase gene regulation through the electrophile response element". Free Radic. Biol. Med. 37 (8): 1152–9. doi:10.1016/j.freeradbiomed.2004.06.011. PMID 15451055.
  • Lebo RV, Kredich NM (1978). "Inactivation of human gamma-glutamylcysteine synthetase by cystamine. Demonstration and quantification of enzyme-ligand complexes". J. Biol. Chem. 253 (8): 2615–23. PMID 24639.
  • Gipp JJ, Chang C, Mulcahy RT (1992). "Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase". Biochem. Biophys. Res. Commun. 185 (1): 29–35. PMID 1350904.
  • Beutler E, Moroose R, Kramer L; et al. (1990). "Gamma-glutamylcysteine synthetase deficiency and hemolytic anemia". Blood. 75 (1): 271–3. PMID 2294991.
  • Konrad PN, Richards F, Valentine WN, Paglia DE (1972). "-Glutamyl-cysteine synthetase deficiency. A cause of hereditary hemolytic anemia". N. Engl. J. Med. 286 (11): 557–61. PMID 5058793.
  • Mulcahy RT, Gipp JJ (1995). "Identification of a putative antioxidant response element in the 5'-flanking region of the human gamma-glutamylcysteine synthetase heavy subunit gene". Biochem. Biophys. Res. Commun. 209 (1): 227–33. doi:10.1006/bbrc.1995.1493. PMID 7726839.
  • Sierra-Rivera E, Summar ML, Dasouki M; et al. (1995). "Assignment of the gene (GLCLC) that encodes the heavy subunit of gamma-glutamylcysteine synthetase to human chromosome 6". Cytogenet. Cell Genet. 70 (3–4): 278–9. PMID 7789189.
  • Kondo T, Yoshida K, Urata Y; et al. (1993). "gamma-Glutamylcysteine synthetase and active transport of glutathione S-conjugate are responsive to heat shock in K562 erythroid cells". J. Biol. Chem. 268 (27): 20366–72. PMID 8104187.
  • Tsuchiya K, Mulcahy RT, Reid LL; et al. (1997). "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". Cytogenet. Cell Genet. 75 (1): 14–6. PMID 8995480.
  • Misra I, Griffith OW (1998). "Expression and purification of human gamma-glutamylcysteine synthetase". Protein Expr. Purif. 13 (2): 268–76. doi:10.1006/prep.1998.0897. PMID 9675072.
  • Tu Z, Anders MW (1999). "Identification of an important cysteine residue in human glutamate-cysteine ligase catalytic subunit by site-directed mutagenesis". Biochem. J. 336 ( Pt 3): 675–80. PMID 9841880.
  • Galloway DC, Blake DG, McLellan LI (1999). "Regulation of gamma-glutamylcysteine synthetase regulatory subunit (GLCLR) gene expression: identification of the major transcriptional start site in HT29 cells". Biochim. Biophys. Acta. 1446 (1–2): 47–56. PMID 10395918.
  • Manna SK, Kuo MT, Aggarwal BB (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 (1999). "The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency". Blood. 94 (8): 2890–4. PMID 10515893.
  • Ristoff E, Augustson C, Geissler J; et al. (2000). "A missense mutation in the heavy subunit of gamma-glutamylcysteine synthetase gene causes hemolytic anemia". Blood. 95 (7): 2193–6. PMID 10733484.
  • Yang H, Wang J, Ou X; et al. (2001). "Cloning and analysis of the rat glutamate-cysteine ligase modifier subunit promoter". Biochem. Biophys. Res. Commun. 285 (2): 476–82. doi:10.1006/bbrc.2001.5190. PMID 11444867.
  • Tatebe S, Sinicrope FA, Kuo MT (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". Biochem. Biophys. Res. Commun. 290 (5): 1427–33. doi:10.1006/bbrc.2002.6367. PMID 11820781.
  • Yang P, Yokomizo A, Tazelaar HD; et al. (2002). "Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes". Lung Cancer. 35 (3): 221–9. PMID 11844594.
  • Ray S, Watkins DN, Misso NL, Thompson PJ (2002). "Oxidant stress induces gamma-glutamylcysteine synthetase and glutathione synthesis in human bronchial epithelial NCI-H292 cells". Clin. Exp. Allergy. 32 (4): 571–7. PMID 11972604.

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