GCLM

Glutamate-cysteine ligase, modifier subunit
Identifiers
Symbols	GCLM ; GLCLR
External IDs	OMIM: 601176 MGI: 104995 HomoloGene: 1557 GeneCards: GCLM Gene
EC number	6.3.2.2
Gene ontology Molecular function • glutamate-cysteine ligase activity • enzyme regulator activity • glutamate-cysteine ligase catalytic subunit binding • protein heterodimerization activity Cellular component • cytosol • glutamate-cysteine ligase complex Biological process • sulfur amino acid metabolic process • cysteine metabolic process • glutamate metabolic process • glutathione biosynthetic process • xenobiotic metabolic process • response to oxidative stress • apoptotic mitochondrial changes • cellular nitrogen compound metabolic process • positive regulation of glutamate-cysteine ligase activity • response to drug • negative regulation of neuron apoptotic process • small molecule metabolic process • regulation of blood vessel size • response to nitrosative stress • regulation of mitochondrial depolarization • glutathione derivative biosynthetic process • negative regulation of extrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2730	14630
Ensembl	ENSG00000023909	ENSMUSG00000028124
UniProt	P48507	O09172
RefSeq (mRNA)	NM_001308253	NM_008129
RefSeq (protein)	NP_001295182	NP_032155
Location (UCSC)	Chr 1: 93.89 – 93.91 Mb	Chr 3: 122.25 – 122.27 Mb
PubMed search

Glutamate-cysteine ligase regulatory subunit is an enzyme that in humans is encoded by the GCLM gene.^[1][2]

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. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia.^[2]

References

1. Gipp JJ, Bailey HH, Mulcahy RT (Feb 1995). "Cloning and sequencing of the cDNA for the light subunit of human liver gamma-glutamylcysteine synthetase and relative mRNA levels for heavy and light subunits in human normal tissues". Biochem Biophys Res Commun 206 (2): 584–9. doi:10.1006/bbrc.1995.1083. PMID 7826375.
2. "Entrez Gene: GCLM glutamate-cysteine ligase, modifier subunit".

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.
• 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. PMID 7829101.
• 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.
• 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. PMID 8978789.
• 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.
• 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. PMID 9841137.
• 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. PMC 1219919. PMID 9841880.
• 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. PMC 1220010. PMID 9895302.
• 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. PMID 10395918.
• 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. PMID 10674357.
• 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. PMID 12081989.
• 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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• 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. PMID 12975258.
• 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. PMID 14532974.
• 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. PMC 528928. PMID 15489334.
• 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. PMID 15946948.
• 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. PMID 16081425.
• 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. PMID 16183645.