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m (fix spelling of author names as listed at https://www.researchgate.net/publication/13446818_Structure_and_refinement_of_the_physical_mapping_of_the_g-glutamylcysteine_ligase_regulatory_subunit_GLCLR_gene_to_chromosome_1p221_within_the_critically_delete...)
 
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{{for|the post-nomial|Legion of Merit (Rhodesia)}}
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{{Infobox_gene}}
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'''Glutamate-cysteine ligase regulatory subunit''' is an [[enzyme]] that in humans is encoded by the ''GCLM'' [[gene]].<ref name="pmid7826375">{{cite journal |vauthors=Gipp JJ, Bailey HH, Mulcahy RT | title = 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 | journal = Biochem Biophys Res Commun | volume = 206 | issue = 2 | pages = 584–9 |date=Feb 1995 | pmid = 7826375 | pmc =  | doi =10.1006/bbrc.1995.1083 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GCLM glutamate-cysteine ligase, modifier subunit| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2730| accessdate = }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Glutamate-cysteine ligase, modifier subunit
| HGNCid = 4312
| Symbol = GCLM
| AltSymbols =; GLCLR
| OMIM = 601176
| ECnumber = 
| Homologene = 1557
| MGIid = 104995
| GeneAtlas_image1 = PBB_GE_GCLM_203925_at_tn.png
| Function = {{GNF_GO|id=GO:0004357 |text = glutamate-cysteine ligase activity}} {{GNF_GO|id=GO:0016491 |text = oxidoreductase activity}} {{GNF_GO|id=GO:0016874 |text = ligase activity}} {{GNF_GO|id=GO:0035226 |text = glutamate-cysteine ligase catalytic subunit binding}}
| Component = {{GNF_GO|id=GO:0005625 |text = soluble fraction}} {{GNF_GO|id=GO:0005829 |text = cytosol}}
| Process = {{GNF_GO|id=GO:0006534 |text = cysteine metabolic process}} {{GNF_GO|id=GO:0006536 |text = glutamate metabolic process}} {{GNF_GO|id=GO:0006750 |text = glutathione biosynthetic process}} {{GNF_GO|id=GO:0006979 |text = response to oxidative stress}} {{GNF_GO|id=GO:0042493 |text = response to drug}} {{GNF_GO|id=GO:0050880 |text = regulation of blood vessel size}}
  | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2730
    | Hs_Ensembl = ENSG00000023909
    | Hs_RefseqProtein = NP_002052
    | Hs_RefseqmRNA = NM_002061
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 94123349
    | Hs_GenLoc_end = 94147554
    | Hs_Uniprot = P48507
    | Mm_EntrezGene = 14630
    | Mm_Ensembl = ENSMUSG00000028124
    | Mm_RefseqmRNA = NM_008129
    | Mm_RefseqProtein = NP_032155
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 3
    | Mm_GenLoc_start = 122237614
    | Mm_GenLoc_end = 122258670
    | Mm_Uniprot = Q3T9P2
  }}
}}
'''Glutamate-cysteine ligase, modifier subunit''', also known as '''GCLM''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: GCLM glutamate-cysteine ligase, modifier subunit| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2730| accessdate = }}</ref>


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{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =  
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: GCLM glutamate-cysteine ligase, modifier subunit| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2730| accessdate = }}</ref>
| summary_text = [[Glutamate-cysteine ligase]], also known as gamma-glutamylcysteine [[ligase|synthetase]], is the first rate limiting enzyme of [[glutathione]] synthesis. The enzyme consists of two subunits, a heavy [[protein subunit|catalytic subuit]] and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of [[hemolytic anemia]].<ref name="entrez" />
}}
}}


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Dickinson DA, Levonen AL, Moellering DR, ''et al.'' |title=Human glutamate cysteine ligase gene regulation through the electrophile response element. |journal=Free Radic. Biol. Med. |volume=37 |issue= 8 |pages= 1152-9 |year= 2005 |pmid= 15451055 |doi= 10.1016/j.freeradbiomed.2004.06.011 }}
*{{cite journal  | author=Dickinson DA |title=Human glutamate cysteine ligase gene regulation through the electrophile response element |journal=Free Radic. Biol. Med. |volume=37 |issue= 8 |pages= 1152–9 |year= 2005 |pmid= 15451055 |doi= 10.1016/j.freeradbiomed.2004.06.011  |name-list-format=vanc| author2=Levonen AL  | author3=Moellering DR  | display-authors=3  | last4=Arnold  | first4=Erin K.  | last5=Zhang  | first5=Hongqiao  | last6=Darley-Usmar | first6=Victor M.  | last7=Forman  | first7=лмлн ЦК кап Henry Jay }}
*{{cite journal | author=Gipp JJ, Bailey HH, Mulcahy RT |title=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. |journal=Biochem. Biophys. Res. Commun. |volume=206 |issue= 2 |pages= 584-9 |year= 1995 |pmid= 7826375 |doi=  }}
*{{cite journal  | author=Robertson NG |title=Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening |journal=Genomics |volume=23 |issue= 1 |pages= 42–50 |year= 1995 |pmid= 7829101 |doi= 10.1006/geno.1994.1457 |name-list-format=vanc| author2=Khetarpal U  | author3=Gutiérrez-Espeleta GA  | display-authors=3  | last4=Bieber  | first4=Frederick R.  | last5=Morton  | first5=Cynthia C. }}
*{{cite journal  | author=Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, ''et al.'' |title=Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening. |journal=Genomics |volume=23 |issue= 1 |pages= 42-50 |year= 1995 |pmid= 7829101 |doi= 10.1006/geno.1994.1457 }}
*{{cite journal  | author=Tsuchiya K |title=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 |journal=Genomics |volume=30 |issue= 3 |pages= 630–2 |year= 1997 |pmid= 8825659 |doi= 10.1006/geno.1995.1293 |name-list-format=vanc| author2=Mulcahy RT | author3=Reid LL  | display-authors=3  | last4=Disteche  | first4=Christine M.  | last5=Kavanagh  | first5=Terrance J. }}
*{{cite journal  | author=Tsuchiya K, Mulcahy RT, Reid LL, ''et al.'' |title=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. |journal=Genomics |volume=30 |issue= 3 |pages= 630-2 |year= 1997 |pmid= 8825659 |doi= 10.1006/geno.1995.1293 }}
*{{cite journal  | author=Sierra-Rivera E |title=Assignment of the human gene (GLCLR) that encodes the regulatory subunit of gamma-glutamylcysteine synthetase to chromosome 1p21 |journal=Cytogenet. Cell Genet. |volume=72 |issue= 2–3 |pages= 252–4 |year= 1997 |pmid= 8978789 |doi=10.1159/000134202 |name-list-format=vanc| author2=Dasouki M  | author3=Summar ML  | display-authors=3 | last4=Krishnamani | first4=M.R.S.  | last5=Meredith  | first5=M.  | last6=Rao | first6=P.N.  | last7=Phillips Iii  | first7=J.A.  | last8=Freeman  | first8=M.L  }}
*{{cite journal  | author=Sierra-Rivera E, Dasouki M, Summar ML, ''et al.'' |title=Assignment of the human gene (GLCLR) that encodes the regulatory subunit of gamma-glutamylcysteine synthetase to chromosome 1p21. |journal=Cytogenet. Cell Genet. |volume=72 |issue= 2-3 |pages= 252-4 |year= 1997 |pmid= 8978789 |doi=  }}
*{{cite journal  |vauthors=Misra I, Griffith OW |title=Expression and purification of human gamma-glutamylcysteine synthetase |journal=Protein Expr. Purif. |volume=13 |issue= 2 |pages= 268–76 |year= 1998 |pmid= 9675072 |doi= 10.1006/prep.1998.0897 }}
*{{cite journal | author=Misra I, Griffith OW |title=Expression and purification of human gamma-glutamylcysteine synthetase. |journal=Protein Expr. Purif. |volume=13 |issue= 2 |pages= 268-76 |year= 1998 |pmid= 9675072 |doi= 10.1006/prep.1998.0897 }}
*{{cite journal  | author=Rozet JM |title=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 |journal=Cytogenet. Cell Genet. |volume=82 |issue= 1–2 |pages= 91–4 |year= 1998 |pmid= 9841137 |doi=10.1159/000015072 |name-list-format=vanc| author2=Gerber S  | author3=Perrault I  | display-authors=3  | last4=Calvas  | first4=P. | last5=Souied  | first5=E.  | last6=Châtelin  | first6=S.  | last7=Viegas-Péquignot | first7=E.  | last8=Molina-Gomez  | first8=D.  | last9=Munnich  | first9=A. }}
*{{cite journal  | author=Rozet JM, Gerber S, Perrault I, ''et al.'' |title=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. |journal=Cytogenet. Cell Genet. |volume=82 |issue= 1-2 |pages= 91-4 |year= 1998 |pmid= 9841137 |doi= }}
*{{cite journal  |vauthors=Tu Z, Anders MW |title=Identification of an important cysteine residue in human glutamate-cysteine ligase catalytic subunit by site-directed mutagenesis |journal=Biochem. J. |volume=336 |issue= 3|pages= 675–80 |year= 1999 |pmid= 9841880 |doi= | pmc=1219919 }}
*{{cite journal | author=Tu Z, Anders MW |title=Identification of an important cysteine residue in human glutamate-cysteine ligase catalytic subunit by site-directed mutagenesis. |journal=Biochem. J. |volume=336 ( Pt 3) |issue=  |pages= 675-80 |year= 1999 |pmid= 9841880 |doi=  }}
*{{cite journal  |vauthors=Tipnis SR, Blake DG, Shepherd AG, McLellan LI |title=Overexpression of the regulatory subunit of gamma-glutamylcysteine synthetase in HeLa cells increases gamma-glutamylcysteine synthetase activity and confers drug resistance |journal=Biochem. J. |volume=337 |issue= 3|pages= 559–66 |year= 1999 |pmid= 9895302 |doi=10.1042/0264-6021:3370559  | pmc=1220010  }}
*{{cite journal  | author=Tipnis SR, Blake DG, Shepherd AG, McLellan LI |title=Overexpression of the regulatory subunit of gamma-glutamylcysteine synthetase in HeLa cells increases gamma-glutamylcysteine synthetase activity and confers drug resistance. |journal=Biochem. J. |volume=337 ( Pt 3) |issue= |pages= 559-66 |year= 1999 |pmid= 9895302 |doi= }}
*{{cite journal  |vauthors=Galloway DC, Blake DG, McLellan LI |title=Regulation of gamma-glutamylcysteine synthetase regulatory subunit (GLCLR) gene expression: identification of the major transcriptional start site in HT29 cells |journal=Biochim. Biophys. Acta |volume=1446 |issue= 1–2 |pages= 47–56 |year= 1999 |pmid= 10395918 |doi= 10.1016/S0167-4781(99)00073-1}}
*{{cite journal  | author=Galloway DC, Blake DG, McLellan LI |title=Regulation of gamma-glutamylcysteine synthetase regulatory subunit (GLCLR) gene expression: identification of the major transcriptional start site in HT29 cells. |journal=Biochim. Biophys. Acta |volume=1446 |issue= 1-2 |pages= 47-56 |year= 1999 |pmid= 10395918 |doi= }}
*{{cite journal  |vauthors=Levonen AL, Lapatto R, Saksela M, Raivio KO |title=Expression of gamma-glutamylcysteine synthetase during development |journal=Pediatr. Res. |volume=47 |issue= 2 |pages= 266–70 |year= 2000 |pmid= 10674357 |doi=10.1203/00006450-200002000-00019 }}
*{{cite journal | author=Levonen AL, Lapatto R, Saksela M, Raivio KO |title=Expression of gamma-glutamylcysteine synthetase during development. |journal=Pediatr. Res. |volume=47 |issue= 2 |pages= 266-70 |year= 2000 |pmid= 10674357 |doi=  }}
*{{cite journal  | author=Nakamura S |title=Polymorphism in the 5'-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction |journal=Circulation |volume=105 |issue= 25 |pages= 2968–73 |year= 2002 |pmid= 12081989 |doi=10.1161/01.CIR.0000019739.66514.1E |name-list-format=vanc| author2=Kugiyama K  | author3=Sugiyama S | display-authors=3  | last4=Miyamoto  | first4=S  | last5=Koide  | first5=S  | last6=Fukushima  | first6=H  | last7=Honda  | first7=O  | last8=Yoshimura  | first8=M  | last9=Ogawa  | first9=H  }}
*{{cite journal  | author=Nakamura S, Kugiyama K, Sugiyama S, ''et al.'' |title=Polymorphism in the 5'-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction. |journal=Circulation |volume=105 |issue= 25 |pages= 2968-73 |year= 2002 |pmid= 12081989 |doi=  }}
*{{cite journal  | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241  |name-list-format=vanc| author2=Feingold EA  | author3=Grouse LH  | display-authors=3  | last4=Derge  | first4=JG  | last5=Klausner  | first5=RD  | last6=Collins  | first6=FS  | last7=Wagner  | first7=L  | last8=Shenmen  | first8=CM  | last9=Schuler  | first9=GD }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Nakamura S |title=Polymorphism in glutamate-cysteine ligase modifier subunit gene is associated with impairment of nitric oxide-mediated coronary vasomotor function |journal=Circulation |volume=108 |issue= 12 |pages= 1425–7 |year= 2003 |pmid= 12975258 |doi= 10.1161/01.CIR.0000091255.63645.98  |name-list-format=vanc| author2=Sugiyama S  | author3=Fujioka D  | display-authors=3  | last4=Kawabata  | first4=K  | last5=Ogawa  | first5=H  | last6=Kugiyama  | first6=K }}
*{{cite journal  | author=Nakamura S, Sugiyama S, Fujioka D, ''et al.'' |title=Polymorphism in glutamate-cysteine ligase modifier subunit gene is associated with impairment of nitric oxide-mediated coronary vasomotor function. |journal=Circulation |volume=108 |issue= 12 |pages= 1425-7 |year= 2003 |pmid= 12975258 |doi= 10.1161/01.CIR.0000091255.63645.98 }}
*{{cite journal  | author=Inoue Y |title=The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer |journal=Int. J. Oncol. |volume=23 |issue= 5 |pages= 1333–9 |year= 2004 |pmid= 14532974 |doi=  10.3892/ijo.23.5.1333|name-list-format=vanc| author2=Tomisawa M  | author3=Yamazaki H  | display-authors=3  | last4=Abe  | first4=Y  | last5=Suemizu  | first5=H  | last6=Tsukamoto  | first6=H  | last7=Tomii  | first7=Y  | last8=Kawamura  | first8=M  | last9=Kijima  | first9=H  }}
*{{cite journal  | author=Inoue Y, Tomisawa M, Yamazaki H, ''et al.'' |title=The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer. |journal=Int. J. Oncol. |volume=23 |issue= 5 |pages= 1333-9 |year= 2004 |pmid= 14532974 |doi=  }}
*{{cite journal  | author=Gerhard DS |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928  |name-list-format=vanc| author2=Wagner L  | author3=Feingold EA  | display-authors=3  | last4=Shenmen  | first4=CM  | last5=Grouse  | first5=LH  | last6=Schuler  | first6=G  | last7=Klein  | first7=SL  | last8=Old  | first8=S  | last9=Rasooly  | first9=R }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  |vauthors=Song IS, Tatebe S, Dai W, Kuo MT |title=Delayed mechanism for induction of gamma-glutamylcysteine synthetase heavy subunit mRNA stability by oxidative stress involving p38 mitogen-activated protein kinase signaling |journal=J. Biol. Chem. |volume=280 |issue= 31 |pages= 28230–40 |year= 2005 |pmid= 15946948 |doi= 10.1074/jbc.M413103200 }}
*{{cite journal | author=Song IS, Tatebe S, Dai W, Kuo MT |title=Delayed mechanism for induction of gamma-glutamylcysteine synthetase heavy subunit mRNA stability by oxidative stress involving p38 mitogen-activated protein kinase signaling. |journal=J. Biol. Chem. |volume=280 |issue= 31 |pages= 28230-40 |year= 2005 |pmid= 15946948 |doi= 10.1074/jbc.M413103200 }}
*{{cite journal  | author=Chen Y |title=Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels |journal=J. Biol. Chem. |volume=280 |issue= 40 |pages= 33766–74 |year= 2005 |pmid= 16081425 |doi= 10.1074/jbc.M504604200  |name-list-format=vanc| author2=Shertzer HG  | author3=Schneider SN  | display-authors=3  | last4=Nebert  | first4=DW  | last5=Dalton  | first5=TP }}
*{{cite journal  | author=Chen Y, Shertzer HG, Schneider SN, ''et al.'' |title=Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels. |journal=J. Biol. Chem. |volume=280 |issue= 40 |pages= 33766-74 |year= 2005 |pmid= 16081425 |doi= 10.1074/jbc.M504604200 }}
*{{cite journal  | author=Diaz-Hernandez JI |title=Knockdown of glutamate-cysteine ligase by small hairpin RNA reveals that both catalytic and modulatory subunits are essential for the survival of primary neurons |journal=J. Biol. Chem. |volume=280 |issue= 47 |pages= 38992–9001 |year= 2006 |pmid= 16183645 |doi= 10.1074/jbc.M507065200 |name-list-format=vanc| author2=Almeida A  | author3=Delgado-Esteban M  | display-authors=3  | last4=Fernandez  | first4=E  | last5=Bolaños  | first5=JP }}
*{{cite journal | author=Diaz-Hernandez JI, Almeida A, Delgado-Esteban M, ''et al.'' |title=Knockdown of glutamate-cysteine ligase by small hairpin RNA reveals that both catalytic and modulatory subunits are essential for the survival of primary neurons. |journal=J. Biol. Chem. |volume=280 |issue= 47 |pages= 38992-9001 |year= 2006 |pmid= 16183645 |doi= 10.1074/jbc.M507065200 }}
}}
}}
{{refend}}
{{refend}}


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Latest revision as of 01:26, 7 August 2018

For the post-nomial, see Legion of Merit (Rhodesia).
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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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Wikidata
View/Edit Human

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 subuit 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. ↑ 2.0 2.1 "Entrez Gene: GCLM glutamate-cysteine ligase, modifier subunit".

Further reading



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