GCLC

Protein-coding gene in the species Homo sapiens

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)^[1]

Band	6p12.1	Start	53,497,341 bp^[1]
Band	6p12.1	End	53,616,970 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 9 (mouse)^[2]

Band	9 E1\|9 43.36 cM	Start	77,661,817 bp^[2]
Band	9 E1\|9 43.36 cM	End	77,701,767 bp^[2]

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 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

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

^[3]

^[4]

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000001084 – Ensembl, May 2017
^ ^a ^b ^c 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.
^ ^a ^b "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.