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)
End	53,616,970 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	77,701,767 bp
RNA expression pattern
	Top expressed in
	bronchial epithelial cell; ; right uterine tube; ; liver; ; islet of Langerhans; ; jejunal mucosa; ; right lobe of liver; ; urinary bladder; ; secondary oocyte; ; corpus callosum; ; spongy bone;
	Top expressed in
	epithelium of stomach; ; left lobe of liver; ; right lung lobe; ; seminal vesicula; ; kidney; ; proximal tubule; ; hair follicle; ; ventromedial nucleus; ; ciliary body; ; mammillary body;
	More reference expression data
	; ;
	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; human 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
	2729
	14629
	ENSG00000001084
	ENSMUSG00000032350
	P48506
	P97494
	NM_001498; NM_001197115
	NM_010295
	NP_001184044; NP_001489
	NP_034425
	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]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000001084 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032350 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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.
1 2 "Entrez Gene: GCLC glutamate-cysteine ligase, catalytic subunit".

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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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000001084 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[pmid1350904-5] 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.

[entrez-6] 1 2 "Entrez Gene: GCLC glutamate-cysteine ligase, catalytic subunit".

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Function

References

Further reading