GCLC

GCLC
Identifiers
AliasesGCLC, GCL, GCS, GLCL, GLCLC, glutamate-cysteine ligase catalytic subunit
External IDsOMIM: 606857 MGI: 104990 HomoloGene: 1148 GeneCards: GCLC
Orthologs
SpeciesHumanMouse
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 MbChr 9: 77.66 – 77.7 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000001084 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032350 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Gipp JJ, Chang C, Mulcahy RT (May 1992). "Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase". Biochemical and Biophysical Research Communications. 185 (1): 29–35. doi:10.1016/S0006-291X(05)80950-7. PMID 1350904.
  6. ^ a b "Entrez Gene: GCLC glutamate-cysteine ligase, catalytic subunit".

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.
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