GCLM

For the post-nomial, seeLegion of Merit (Rhodesia).

GCLM
Identifiers
Aliases	GCLM,GLCLR, glutamate-cysteine ligase modifier subunit
External IDs	OMIM:601176;MGI:104995;HomoloGene:1557;GeneCards:GCLM;OMA:GCLM - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p22.1 Start 93,885,199bp End 93,909,456bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3 G1|3 52.94 cM Start 122,039,206bp End 122,064,381bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in bronchial epithelial cell islet of Langerhans jejunal mucosa hair follicle secondary oocyte cartilage tissue Skeletal muscle tissue of rectus abdominis epithelium of nasopharynx duodenum trabecular bone Top expressed in right kidney stroma of bone marrow blood fetal liver hematopoietic progenitor cell left lobe of liver human kidney tibiofemoral joint pyloric antrum lacrimal gland facial motor nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function enzyme regulator activity glutamate-cysteine ligase catalytic subunit binding protein heterodimerization activity glutamate-cysteine ligase activity Cellular component cytosol glutamate-cysteine ligase complex Biological process negative regulation of neuron apoptotic process glutathione metabolic process cysteine metabolic process negative regulation of extrinsic apoptotic signaling pathway regulation of mitochondrial depolarization apoptotic mitochondrial changes response to nitrosative stress glutamate metabolic process glutathione biosynthetic process positive regulation of glutamate-cysteine ligase activity response to oxidative stress human ageing cellular response to thyroxine stimulus hepatic stellate cell activation cellular response to follicle-stimulating hormone stimulus cellular response to fibroblast growth factor stimulus response to human chorionic gonadotropin response to nutrient response to activity cellular response to hepatocyte growth factor stimulus cellular response to glucose stimulus cellular response to leukemia inhibitory factor Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 2730 14630 Ensembl ENSG00000023909 ENSMUSG00000028124 UniProt P48507 O09172 RefSeq (mRNA) NM_001308253 NM_002061 NM_008129 RefSeq (protein) NP_001295182 NP_002052 NP_032155 Location (UCSC) Chr 1: 93.89 – 93.91 Mb Chr 3: 122.04 – 122.06 Mb PubMedsearch
Wikidata
View/Edit Human View/Edit Mouse

Glutamate-cysteine ligase regulatory subunitis anenzymethat in humans is encoded by theGCLMgene.

Glutamate-cysteine ligase,also known as gamma-glutamylcysteinesynthetase,is the first rate limiting enzyme ofglutathionesynthesis. The enzyme consists of two subunits, a heavycatalytic subunitand a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms ofhemolytic anemia.

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.PMID15451055.
• Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, et al. (1995). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening".Genomics.23(1): 42–50.doi:10.1006/geno.1994.1457.PMID7829101.
• 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.PMID8825659.
• Sierra-Rivera E, Dasouki M, Summar ML, et al. (1997). "Assignment of the human gene (GLCLR) that encodes the regulatory subunit of gamma-glutamylcysteine synthetase to chromosome 1p21".Cytogenet. Cell Genet.72(2–3): 252–4.doi:10.1159/000134202.PMID8978789.
• 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.PMID9675072.
• Rozet JM, Gerber S, Perrault I, et al. (1998). "Structure and refinement of the physical mapping of the gamma- glutamylcysteine ligase regulatory subunit (GLCLR) gene to chromosome 1p22.1 within the critically deleted region of human malignant mesothelioma".Cytogenet. Cell Genet.82(1–2): 91–4.doi:10.1159/000015072.PMID9841137.S2CID46772373.
• 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(3): 675–80.doi:10.1042/bj3360675.PMC1219919.PMID9841880.
• Tipnis SR, Blake DG, Shepherd AG, McLellan LI (1999)."Overexpression of the regulatory subunit of gamma-glutamylcysteine synthetase in HeLa cells increases gamma-glutamylcysteine synthetase activity and confers drug resistance".Biochem. J.337(3): 559–66.doi:10.1042/0264-6021:3370559.PMC1220010.PMID9895302.
• 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.doi:10.1016/S0167-4781(99)00073-1.PMID10395918.
• Levonen AL, Lapatto R, Saksela M, Raivio KO (2000)."Expression of gamma-glutamylcysteine synthetase during development".Pediatr. Res.47(2): 266–70.doi:10.1203/00006450-200002000-00019.PMID10674357.
• Nakamura S, Kugiyama K, Sugiyama S, et al. (2002)."Polymorphism in the 5'-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction".Circulation.105(25): 2968–73.doi:10.1161/01.CIR.0000019739.66514.1E.PMID12081989.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003)."Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences".Proc. Natl. Acad. Sci. U.S.A.99(26): 16899–903.Bibcode:2002PNAS...9916899M.doi:10.1073/pnas.242603899.PMC139241.PMID12477932.
• Nakamura S, Sugiyama S, Fujioka D, et al. (2003)."Polymorphism in glutamate-cysteine ligase modifier subunit gene is associated with impairment of nitric oxide-mediated coronary vasomotor function".Circulation.108(12): 1425–7.doi:10.1161/01.CIR.0000091255.63645.98.PMID12975258.
• Inoue Y, Tomisawa M, Yamazaki H, et al. (2004). "The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer".Int. J. Oncol.23(5): 1333–9.doi:10.3892/ijo.23.5.1333.PMID14532974.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004)."The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)".Genome Res.14(10B): 2121–7.doi:10.1101/gr.2596504.PMC528928.PMID15489334.
• Song IS, Tatebe S, Dai W, Kuo MT (2005)."Delayed mechanism for induction of gamma-glutamylcysteine synthetase heavy subunit mRNA stability by oxidative stress involving p38 mitogen-activated protein kinase signaling".J. Biol. Chem.280(31): 28230–40.doi:10.1074/jbc.M413103200.PMID15946948.
• Chen Y, Shertzer HG, Schneider SN, et al. (2005)."Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels".J. Biol. Chem.280(40): 33766–74.doi:10.1074/jbc.M504604200.PMID16081425.
• Diaz-Hernandez JI, Almeida A, Delgado-Esteban M, et al. (2006)."Knockdown of glutamate-cysteine ligase by small hairpin RNA reveals that both catalytic and modulatory subunits are essential for the survival of primary neurons".J. Biol. Chem.280(47): 38992–9001.doi:10.1074/jbc.M507065200.PMID16183645.