GCLC

From Wikipedia, the free encyclopedia

Glutamate-cysteine ligase, catalytic subunit

Identifiers

GCLC; GCS; GLCL; GLCLC

External IDs

OMIM: 606857 MGI: 104990 HomoloGene: 1148

Gene ontology
Molecular Function:	• magnesium ion binding • glutamate-cysteine ligase activity • glutamate binding • ligase activity • ADP binding • coenzyme binding
Biological Process:	• cysteine metabolic process • glutamate metabolic process • glutathione biosynthetic process • anti-apoptosis • response to oxidative stress • response to heat • response to hormone stimulus • negative regulation of transcription • regulation of cell redox homeostasis • regulation of blood vessel size

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_001498 (mRNA)
NP_001489 (protein)

NM_010295 (mRNA)
NP_034425 (protein)

Location

Chr 6: 53.47 - 53.52 Mb

Chr 9: 77.54 - 77.58 Mb

Pubmed search

[1]

[2]

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]

[edit] References

^ ^a ^b Entrez Gene: GCLC glutamate-cysteine ligase, catalytic subunit.

[edit] 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.