GCLM

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)
End	93,909,456 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	122,064,381 bp
RNA expression pattern
	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
	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; 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
	2730
	14630
	ENSG00000023909
	ENSMUSG00000028124
	P48507
	O09172
	NM_001308253; NM_002061
	NM_008129
	NP_001295182; NP_002052
	NP_032155
	Wikidata
View/Edit Human	View/Edit Mouse

Glutamate-cysteine ligase regulatory subunit is an enzyme that in humans is encoded by the GCLM gene.⁵⁶

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.⁶

References

GRCh38: Ensembl release 89: ENSG00000023909 – Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000028124 – 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, 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.
"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. hdl:10669/15162. 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. S2CID 46772373.
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. 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. Bibcode:2002PNAS...9916899M. 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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000023909 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028124 – 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.

[pmid7826375-5] 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.

[entrez-6] "Entrez Gene: GCLM glutamate-cysteine ligase, modifier subunit".

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