Full text data of GCLM
GCLM
(GLCLR)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Glutamate--cysteine ligase regulatory subunit (GCS light chain; Gamma-ECS regulatory subunit; Gamma-glutamylcysteine synthetase regulatory subunit; Glutamate--cysteine ligase modifier subunit)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Glutamate--cysteine ligase regulatory subunit (GCS light chain; Gamma-ECS regulatory subunit; Gamma-glutamylcysteine synthetase regulatory subunit; Glutamate--cysteine ligase modifier subunit)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00010090
IPI00010090 Glutamate--cysteine ligase regulatory subunit Glutathione biosynthesis; first step, ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00010090 Glutamate--cysteine ligase regulatory subunit Glutathione biosynthesis; first step, ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P48507
ID GSH0_HUMAN Reviewed; 274 AA.
AC P48507; A8K334; D3DT45; Q6FHC1; Q9NPX9; Q9NU74;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 1.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=Glutamate--cysteine ligase regulatory subunit;
DE AltName: Full=GCS light chain;
DE AltName: Full=Gamma-ECS regulatory subunit;
DE AltName: Full=Gamma-glutamylcysteine synthetase regulatory subunit;
DE AltName: Full=Glutamate--cysteine ligase modifier subunit;
GN Name=GCLM; Synonyms=GLCLR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=7826375; DOI=10.1006/bbrc.1995.1083;
RA Gipp J.J., Bailey H.H., Mulcahy R.T.;
RT "Cloning and sequencing of the cDNA for the light subunit of human
RT liver gamma-glutamylcysteine synthetase and relative mRNA levels for
RT heavy and light subunits in human normal tissues.";
RL Biochem. Biophys. Res. Commun. 206:584-589(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-209.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-263, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione
CC from L-cysteine and L-glutamate: step 1/2.
CC -!- SUBUNIT: Heterodimer of a catalytic heavy chain and a regulatory
CC light chain.
CC -!- TISSUE SPECIFICITY: In all tissues examined. Highest levels in
CC skeletal muscle.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Glutamate--
CC cysteine ligase light chain subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gclm/";
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DR EMBL; L35546; AAA65028.1; -; mRNA.
DR EMBL; CR541833; CAG46632.1; -; mRNA.
DR EMBL; AY773965; AAV28733.1; -; Genomic_DNA.
DR EMBL; AK290449; BAF83138.1; -; mRNA.
DR EMBL; AL049796; CAI21813.1; -; Genomic_DNA.
DR EMBL; AL117351; CAI21813.1; JOINED; Genomic_DNA.
DR EMBL; AL117351; CAI22976.1; -; Genomic_DNA.
DR EMBL; AL049796; CAI22976.1; JOINED; Genomic_DNA.
DR EMBL; CH471097; EAW73060.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73061.1; -; Genomic_DNA.
DR EMBL; BC041809; AAH41809.1; -; mRNA.
DR PIR; JC2474; JC2474.
DR RefSeq; NP_002052.1; NM_002061.2.
DR UniGene; Hs.315562; -.
DR ProteinModelPortal; P48507; -.
DR IntAct; P48507; 3.
DR STRING; 9606.ENSP00000359258; -.
DR DrugBank; DB00151; L-Cysteine.
DR DrugBank; DB00142; L-Glutamic Acid.
DR PhosphoSite; P48507; -.
DR DMDM; 1346188; -.
DR OGP; P48507; -.
DR PaxDb; P48507; -.
DR PeptideAtlas; P48507; -.
DR PRIDE; P48507; -.
DR DNASU; 2730; -.
DR Ensembl; ENST00000370238; ENSP00000359258; ENSG00000023909.
DR GeneID; 2730; -.
DR KEGG; hsa:2730; -.
DR UCSC; uc001dqg.1; human.
DR CTD; 2730; -.
DR GeneCards; GC01M094351; -.
DR HGNC; HGNC:4312; GCLM.
DR HPA; CAB009568; -.
DR HPA; CAB040554; -.
DR HPA; HPA023696; -.
DR MIM; 601176; gene+phenotype.
DR neXtProt; NX_P48507; -.
DR PharmGKB; PA28613; -.
DR eggNOG; COG0656; -.
DR HOGENOM; HOG000007111; -.
DR HOVERGEN; HBG005923; -.
DR InParanoid; P48507; -.
DR KO; K11205; -.
DR OMA; LEWVLRY; -.
DR OrthoDB; EOG7B5WWG; -.
DR PhylomeDB; P48507; -.
DR BioCyc; MetaCyc:ENSG00000023909-MONOMER; -.
DR BRENDA; 6.3.2.2; 2681.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00142; UER00209.
DR ChiTaRS; GCLM; human.
DR GeneWiki; GCLM; -.
DR GenomeRNAi; 2730; -.
DR NextBio; 10760; -.
DR PRO; PR:P48507; -.
DR ArrayExpress; P48507; -.
DR Bgee; P48507; -.
DR CleanEx; HS_GCLM; -.
DR Genevestigator; P48507; -.
DR GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR GO; GO:0017109; C:glutamate-cysteine ligase complex; IEA:Ensembl.
DR GO; GO:0006534; P:cysteine metabolic process; IEA:Ensembl.
DR GO; GO:0006536; P:glutamate metabolic process; IDA:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; IDA:UniProtKB.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0035229; P:positive regulation of glutamate-cysteine ligase activity; IEA:Ensembl.
DR GO; GO:0050880; P:regulation of blood vessel size; IMP:UniProtKB.
DR GO; GO:0051900; P:regulation of mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IDA:UniProtKB.
DR GO; GO:0051409; P:response to nitrosative stress; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Glutathione biosynthesis;
KW Polymorphism; Reference proteome.
FT CHAIN 1 274 Glutamate--cysteine ligase regulatory
FT subunit.
FT /FTId=PRO_0000192573.
FT MOD_RES 263 263 N6-acetyllysine.
FT VARIANT 209 209 I -> M (in dbSNP:rs17880087).
FT /FTId=VAR_021063.
SQ SEQUENCE 274 AA; 30727 MW; 88F73E22322E40B2 CRC64;
MGTDSRAAKA LLARARTLHL QTGNLLNWGR LRKKCPSTHS EELHDCIQKT LNEWSSQINP
DLVREFPDVL ECTVSHAVEK INPDEREEMK VSAKLFIVES NSSSSTRSAV DMACSVLGVA
QLDSVIIASP PIEDGVNLSL EHLQPYWEEL ENLVQSKKIV AIGTSDLDKT QLEQLYQWAQ
VKPNSNQVNL ASCCVMPPDL TAFAKQFDIQ LLTHNDPKEL LSEASFQEAL QESIPDIQAH
EWVPLWLLRY SVIVKSRGII KSKGYILQAK RRGS
//
ID GSH0_HUMAN Reviewed; 274 AA.
AC P48507; A8K334; D3DT45; Q6FHC1; Q9NPX9; Q9NU74;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 1.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=Glutamate--cysteine ligase regulatory subunit;
DE AltName: Full=GCS light chain;
DE AltName: Full=Gamma-ECS regulatory subunit;
DE AltName: Full=Gamma-glutamylcysteine synthetase regulatory subunit;
DE AltName: Full=Glutamate--cysteine ligase modifier subunit;
GN Name=GCLM; Synonyms=GLCLR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=7826375; DOI=10.1006/bbrc.1995.1083;
RA Gipp J.J., Bailey H.H., Mulcahy R.T.;
RT "Cloning and sequencing of the cDNA for the light subunit of human
RT liver gamma-glutamylcysteine synthetase and relative mRNA levels for
RT heavy and light subunits in human normal tissues.";
RL Biochem. Biophys. Res. Commun. 206:584-589(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-209.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-263, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione
CC from L-cysteine and L-glutamate: step 1/2.
CC -!- SUBUNIT: Heterodimer of a catalytic heavy chain and a regulatory
CC light chain.
CC -!- TISSUE SPECIFICITY: In all tissues examined. Highest levels in
CC skeletal muscle.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Glutamate--
CC cysteine ligase light chain subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gclm/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L35546; AAA65028.1; -; mRNA.
DR EMBL; CR541833; CAG46632.1; -; mRNA.
DR EMBL; AY773965; AAV28733.1; -; Genomic_DNA.
DR EMBL; AK290449; BAF83138.1; -; mRNA.
DR EMBL; AL049796; CAI21813.1; -; Genomic_DNA.
DR EMBL; AL117351; CAI21813.1; JOINED; Genomic_DNA.
DR EMBL; AL117351; CAI22976.1; -; Genomic_DNA.
DR EMBL; AL049796; CAI22976.1; JOINED; Genomic_DNA.
DR EMBL; CH471097; EAW73060.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73061.1; -; Genomic_DNA.
DR EMBL; BC041809; AAH41809.1; -; mRNA.
DR PIR; JC2474; JC2474.
DR RefSeq; NP_002052.1; NM_002061.2.
DR UniGene; Hs.315562; -.
DR ProteinModelPortal; P48507; -.
DR IntAct; P48507; 3.
DR STRING; 9606.ENSP00000359258; -.
DR DrugBank; DB00151; L-Cysteine.
DR DrugBank; DB00142; L-Glutamic Acid.
DR PhosphoSite; P48507; -.
DR DMDM; 1346188; -.
DR OGP; P48507; -.
DR PaxDb; P48507; -.
DR PeptideAtlas; P48507; -.
DR PRIDE; P48507; -.
DR DNASU; 2730; -.
DR Ensembl; ENST00000370238; ENSP00000359258; ENSG00000023909.
DR GeneID; 2730; -.
DR KEGG; hsa:2730; -.
DR UCSC; uc001dqg.1; human.
DR CTD; 2730; -.
DR GeneCards; GC01M094351; -.
DR HGNC; HGNC:4312; GCLM.
DR HPA; CAB009568; -.
DR HPA; CAB040554; -.
DR HPA; HPA023696; -.
DR MIM; 601176; gene+phenotype.
DR neXtProt; NX_P48507; -.
DR PharmGKB; PA28613; -.
DR eggNOG; COG0656; -.
DR HOGENOM; HOG000007111; -.
DR HOVERGEN; HBG005923; -.
DR InParanoid; P48507; -.
DR KO; K11205; -.
DR OMA; LEWVLRY; -.
DR OrthoDB; EOG7B5WWG; -.
DR PhylomeDB; P48507; -.
DR BioCyc; MetaCyc:ENSG00000023909-MONOMER; -.
DR BRENDA; 6.3.2.2; 2681.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00142; UER00209.
DR ChiTaRS; GCLM; human.
DR GeneWiki; GCLM; -.
DR GenomeRNAi; 2730; -.
DR NextBio; 10760; -.
DR PRO; PR:P48507; -.
DR ArrayExpress; P48507; -.
DR Bgee; P48507; -.
DR CleanEx; HS_GCLM; -.
DR Genevestigator; P48507; -.
DR GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR GO; GO:0017109; C:glutamate-cysteine ligase complex; IEA:Ensembl.
DR GO; GO:0006534; P:cysteine metabolic process; IEA:Ensembl.
DR GO; GO:0006536; P:glutamate metabolic process; IDA:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; IDA:UniProtKB.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0035229; P:positive regulation of glutamate-cysteine ligase activity; IEA:Ensembl.
DR GO; GO:0050880; P:regulation of blood vessel size; IMP:UniProtKB.
DR GO; GO:0051900; P:regulation of mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IDA:UniProtKB.
DR GO; GO:0051409; P:response to nitrosative stress; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Glutathione biosynthesis;
KW Polymorphism; Reference proteome.
FT CHAIN 1 274 Glutamate--cysteine ligase regulatory
FT subunit.
FT /FTId=PRO_0000192573.
FT MOD_RES 263 263 N6-acetyllysine.
FT VARIANT 209 209 I -> M (in dbSNP:rs17880087).
FT /FTId=VAR_021063.
SQ SEQUENCE 274 AA; 30727 MW; 88F73E22322E40B2 CRC64;
MGTDSRAAKA LLARARTLHL QTGNLLNWGR LRKKCPSTHS EELHDCIQKT LNEWSSQINP
DLVREFPDVL ECTVSHAVEK INPDEREEMK VSAKLFIVES NSSSSTRSAV DMACSVLGVA
QLDSVIIASP PIEDGVNLSL EHLQPYWEEL ENLVQSKKIV AIGTSDLDKT QLEQLYQWAQ
VKPNSNQVNL ASCCVMPPDL TAFAKQFDIQ LLTHNDPKEL LSEASFQEAL QESIPDIQAH
EWVPLWLLRY SVIVKSRGII KSKGYILQAK RRGS
//
MIM
601176
*RECORD*
*FIELD* NO
601176
*FIELD* TI
*601176 GLUTAMATE-CYSTEINE LIGASE, MODIFIER SUBUNIT; GCLM
;;GLUTAMATE-CYSTEINE LIGASE, REGULATORY; GLCLR;;
read moreGAMMA-GLUTAMYLCYSTEINE SYNTHETASE, REGULATORY SUBUNIT
*FIELD* TX
DESCRIPTION
Gamma-glutamylcysteine synthetase, also known as glutamate-cysteine
ligase (EC 6.3.2.2), is the first rate-limiting enzyme in glutathione
biosynthesis.
CLONING
Human liver gamma-glutamylcysteine synthetase consists of 2 subunits: a
heavy catalytic subunit (GCLC; 606857) and a light regulatory subunit.
Gipp et al. (1995) reported the cloning of a full-length cDNA for the
light subunit. The cDNA encodes a 274-amino acid protein of
approximately 30.7 kD that is 96% identical to the previously cloned rat
sequence (Huang et al., 1993). Northern blot analysis detected 1.4- and
4.1-kb transcripts in several tissue types. The smaller transcript was
detected in the colon, whereas both forms were found in skeletal muscle.
GENE STRUCTURE
Rozet et al. (1998) determined that the GLCLR gene encompasses 22 kb and
contains 7 exons.
MAPPING
By fluorescence in situ hybridization (FISH), Tsuchiya et al. (1995)
mapped the human GLCLR gene to 1p22-p21 and the mouse gene to 3H1-3. By
Southern blot analysis of DNA from a panel of somatic cell hybrids,
Sierra-Rivera et al. (1996) assigned GLCLR to chromosome 1;
sublocalization to 1p21 was achieved by FISH.
Rozet et al. (1998) found an EST of GLCLR within a YAC contig
encompassing the critically deleted region of human malignant
mesothelioma, between loci D1S435 and D1S236. They refined the physical
mapping of GLCLR to 1p22.1.
MOLECULAR GENETICS
Nakamura et al. (2002) reported an association between a polymorphism in
the GCLM gene (601176.0001) and myocardial infarction (608446).
Schizophrenia (181500) is a major and frequent chronic psychiatric
disorder with a strong genetic component. Converging evidence points to
the involvement of oxidative stress and N-methyl D-aspartate (NMDA)
receptor (138249) hypofunction in the pathophysiology of the disease. As
a main cellular nonprotein antioxidant and redox regulator, glutathione
(GSH) plays a major role in protecting nervous tissue against reactive
oxygen species and in modulating redox-sensitive sites, including NMDA
receptors (NMDA-R). Tosic et al. (2006) noted that studies had found GSH
levels to be decreased in patients' cerebrospinal fluid, in medial
prefrontal cortex in vivo, and in striatum postmortem tissue.
GSH-deficient models revealed morphologic, electrophysiologic, and
behavioral anomalies similar to those observed in patients. Tosic et al.
(2006) found an association between schizophrenia and the gene of the
key GSH-synthesizing enzyme, GCLM. A functional role of the GCLM gene
variance in schizophrenia was supported by its low expression in
patients' fibroblasts and by the decreased stimulation of the enzyme
activity when challenged by an oxidative stress. The findings were
considered consistent with the concept that an abnormal GSH metabolism
is a factor for schizophrenia. One of the case-control studies was
conducted in Switzerland and the other in Denmark. Two particular
combinations of variation at 3 SNPs related to the GCLM gene, TT/GG/TC
and CC/GG/TT, had odds ratios of 4.89 and 4.17, respectively. Tosic et
al. (2006) observed that the GCLM gene is localized on 1p21, a region
shown by previous linkage studies to be one of the several critical for
schizophrenia (Pulver et al., 2000, Arinami et al., 2005).
*FIELD* AV
.0001
MYOCARDIAL INFARCTION, SUSCEPTIBILITY TO
GCLM, -588C-T
In Japanese patients with myocardial infarction (608446), Nakamura et
al. (2002) searched for common variants in the 5-prime flanking region
of the GCLM gene and identified a -588C-T polymorphism in which the T
allele showed lower promoter activity (40 to 50% of that of the C
allele) in response to oxidants. Analyzing 429 patients with MI and 428
controls, the authors found that the frequency of the T polymorphism was
significantly higher in the MI group than in the control group (p less
than 0.001). In multiple logistic regression analysis, the T
polymorphism was a risk factor for MI independent of traditional
coronary artery disease risk factors (OR = 1.98, 95% CI = 1.38-2.83, p
less than 0.001). Nakamura et al. (2002) suggested that the -588T
polymorphism may suppress oxidant induction of the GCLM gene and that it
is a risk factor for MI.
Nakamura et al. (2003) examined the effects of the -588C-T polymorphism
on coronary arterial diameter and blood flow responses to intracoronary
infusion of acetylcholine in 157 consecutive patients with normal
coronary angiograms. In multivariate linear regression analysis with
covariates including traditional risk factors, the minor -588T allele
had an independent association with impaired dilation of epicardial
coronary arteries in response to acetylcholine (p less than 0.001), and
it was independently associated with a blunted increase in coronary flow
response to acetylcholine (p less than 0.01). In a subgroup of 59
consecutive patients, constrictor responses to intracoronary infusion of
NG-monomethyl-L-arginine monoacetate, had an inverse and independent
association with the -558T allele in multivariate analysis (p less than
0.01). Nakamura et al. (2003) concluded that the -588T polymorphism
causes a decrease in endothelial nitric oxide bioactivity, leading to
impairment of endothelium-dependent vasomotor function in large and
resistance coronary arteries.
*FIELD* RF
1. Arinami, T.; Ohtsuki, T.; Ishiguro, H.; Ujike, H.; Tanaka, Y.;
Morita, Y.; Mineta, M.; Takeichi, M.; Yamada, S.; Imamura, A.; Ohara,
K.; Shibuya, H.; and 40 others: Genomewide high-density SNP linkage
analysis of 236 Japanese families supports the existence of schizophrenia
susceptibility loci on chromosomes 1p, 14q, and 20p. Am. J. Hum.
Genet. 77: 937-944, 2005.
2. Gipp, J. J.; Bailey, H. H.; Mulcahy, R. T.: 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: 584-589,
1995.
3. Huang, C.-S.; Anderson, M. E.; Meister, A.: Amino acid sequence
and function of the light subunit of rat kidney gamma-glutamylcysteine
synthetase. J. Biol. Chem. 268: 20578-20583, 1993.
4. Nakamura, S.; Kugiyama, K.; Sugiyama, S.; Miyamoto, S.; Koide,
S.; Fukushima, H.; Honda, O.; Yoshimura, M.; Ogawa, H.: Polymorphism
in the 5-prime-flanking region of human glutamate-cysteine ligase
modifier subunit gene is associated with myocardial infarction. Circulation 105:
2968-2973, 2002.
5. Nakamura, S.; Sugiyama, S.; Fujioka, D.; Kawabata, K.; Ogawa, H.;
Kugiyama, K.: Polymorphism in glutamate-cysteine ligase modifier
subunit gene is associated with impairment of nitric oxide-mediated
coronary vasomotor function. Circulation 108: 1425-1427, 2003.
6. Pulver, A. E.; Mulle, J.; Nestadt, G.; Swartz, K. L.; Blouin, J.-L.;
Dombroski, B.; Liang, K.-Y.; Housman, D. E.; Kazazian, H. H.; Antonarakis,
S. E.; Lasseter, V. K.; Wolyniec, P. S.; Thornquist, M. H.; McGrath,
J. A.: Genetic heterogeneity in schizophrenia: stratification of
genome scan data using co-segregating related phenotypes. Molec.
Psychiat. 5: 650-653, 2000.
7. Rozet, J.-M.; Gerber, S.; Perrault, I.; Calvas, P.; Souied, E.;
Chatelin, S.; Viegas-Pequignot, E.; Molina-Gomez, D.; Munnich, A.;
Kaplan, J.: Structure and refinement of the physical mapping of the
gamma-glutamylcysteine ligase regulatory subunit (GLCLR) gene to chromosome
1pp22.1 within the critically deleted region of human malignant mesothelioma. Cytogenet.
Cell Genet. 82: 91-94, 1998.
8. Sierra-Rivera, E.; Dasouki, M.; Summar, M. L.; Krishnamani, M.
R. S.; Meredith, M.; Rao, P. N.; Phillips, J. A., III; Freeman, M.
L.: Assignment of the human gene (GLCLR) that encodes the regulatory
subunit of gamma-glutamylcysteine synthetase to chromosome 1p21. Cytogenet.
Cell Genet. 72: 252-254, 1996.
9. Tosic, M.; Ott, J.; Barral, S.; Bovet, P.; Deppen, P.; Gheorghita,
F.; Matthey, M.-L.; Parnas, J.; Preisig, M.; Saraga, M.; Solida, A.;
Timm, S.; Wang, A. G.; Werge, T.; Cuenod, M.; Do, K. Q.: Schizophrenia
and oxidative stress: glutamate cysteine ligase modifier as a susceptibility
gene. Am. J. Hum. Genet. 79: 586-592, 2006.
10. Tsuchiya, K.; Mulcahy, R. T.; Reid, L. L.; Disteche, C. M.; Kavanagh,
T. J.: 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: 630-632, 1995.
*FIELD* CN
Victor A. McKusick - updated: 8/23/2006
Carol A. Bocchini - updated: 12/9/1998
*FIELD* CD
Alan F. Scott: 4/4/1996
*FIELD* ED
carol: 11/02/2011
ckniffin: 4/8/2011
terry: 9/17/2007
carol: 2/27/2007
alopez: 8/28/2006
terry: 8/23/2006
tkritzer: 9/9/2004
carol: 11/5/2003
carol: 4/17/2002
carol: 11/13/2000
terry: 12/9/1998
dkim: 12/7/1998
carol: 7/30/1998
alopez: 5/13/1997
terry: 6/12/1996
terry: 6/6/1996
mark: 4/4/1996
terry: 4/4/1996
mark: 4/4/1996
*RECORD*
*FIELD* NO
601176
*FIELD* TI
*601176 GLUTAMATE-CYSTEINE LIGASE, MODIFIER SUBUNIT; GCLM
;;GLUTAMATE-CYSTEINE LIGASE, REGULATORY; GLCLR;;
read moreGAMMA-GLUTAMYLCYSTEINE SYNTHETASE, REGULATORY SUBUNIT
*FIELD* TX
DESCRIPTION
Gamma-glutamylcysteine synthetase, also known as glutamate-cysteine
ligase (EC 6.3.2.2), is the first rate-limiting enzyme in glutathione
biosynthesis.
CLONING
Human liver gamma-glutamylcysteine synthetase consists of 2 subunits: a
heavy catalytic subunit (GCLC; 606857) and a light regulatory subunit.
Gipp et al. (1995) reported the cloning of a full-length cDNA for the
light subunit. The cDNA encodes a 274-amino acid protein of
approximately 30.7 kD that is 96% identical to the previously cloned rat
sequence (Huang et al., 1993). Northern blot analysis detected 1.4- and
4.1-kb transcripts in several tissue types. The smaller transcript was
detected in the colon, whereas both forms were found in skeletal muscle.
GENE STRUCTURE
Rozet et al. (1998) determined that the GLCLR gene encompasses 22 kb and
contains 7 exons.
MAPPING
By fluorescence in situ hybridization (FISH), Tsuchiya et al. (1995)
mapped the human GLCLR gene to 1p22-p21 and the mouse gene to 3H1-3. By
Southern blot analysis of DNA from a panel of somatic cell hybrids,
Sierra-Rivera et al. (1996) assigned GLCLR to chromosome 1;
sublocalization to 1p21 was achieved by FISH.
Rozet et al. (1998) found an EST of GLCLR within a YAC contig
encompassing the critically deleted region of human malignant
mesothelioma, between loci D1S435 and D1S236. They refined the physical
mapping of GLCLR to 1p22.1.
MOLECULAR GENETICS
Nakamura et al. (2002) reported an association between a polymorphism in
the GCLM gene (601176.0001) and myocardial infarction (608446).
Schizophrenia (181500) is a major and frequent chronic psychiatric
disorder with a strong genetic component. Converging evidence points to
the involvement of oxidative stress and N-methyl D-aspartate (NMDA)
receptor (138249) hypofunction in the pathophysiology of the disease. As
a main cellular nonprotein antioxidant and redox regulator, glutathione
(GSH) plays a major role in protecting nervous tissue against reactive
oxygen species and in modulating redox-sensitive sites, including NMDA
receptors (NMDA-R). Tosic et al. (2006) noted that studies had found GSH
levels to be decreased in patients' cerebrospinal fluid, in medial
prefrontal cortex in vivo, and in striatum postmortem tissue.
GSH-deficient models revealed morphologic, electrophysiologic, and
behavioral anomalies similar to those observed in patients. Tosic et al.
(2006) found an association between schizophrenia and the gene of the
key GSH-synthesizing enzyme, GCLM. A functional role of the GCLM gene
variance in schizophrenia was supported by its low expression in
patients' fibroblasts and by the decreased stimulation of the enzyme
activity when challenged by an oxidative stress. The findings were
considered consistent with the concept that an abnormal GSH metabolism
is a factor for schizophrenia. One of the case-control studies was
conducted in Switzerland and the other in Denmark. Two particular
combinations of variation at 3 SNPs related to the GCLM gene, TT/GG/TC
and CC/GG/TT, had odds ratios of 4.89 and 4.17, respectively. Tosic et
al. (2006) observed that the GCLM gene is localized on 1p21, a region
shown by previous linkage studies to be one of the several critical for
schizophrenia (Pulver et al., 2000, Arinami et al., 2005).
*FIELD* AV
.0001
MYOCARDIAL INFARCTION, SUSCEPTIBILITY TO
GCLM, -588C-T
In Japanese patients with myocardial infarction (608446), Nakamura et
al. (2002) searched for common variants in the 5-prime flanking region
of the GCLM gene and identified a -588C-T polymorphism in which the T
allele showed lower promoter activity (40 to 50% of that of the C
allele) in response to oxidants. Analyzing 429 patients with MI and 428
controls, the authors found that the frequency of the T polymorphism was
significantly higher in the MI group than in the control group (p less
than 0.001). In multiple logistic regression analysis, the T
polymorphism was a risk factor for MI independent of traditional
coronary artery disease risk factors (OR = 1.98, 95% CI = 1.38-2.83, p
less than 0.001). Nakamura et al. (2002) suggested that the -588T
polymorphism may suppress oxidant induction of the GCLM gene and that it
is a risk factor for MI.
Nakamura et al. (2003) examined the effects of the -588C-T polymorphism
on coronary arterial diameter and blood flow responses to intracoronary
infusion of acetylcholine in 157 consecutive patients with normal
coronary angiograms. In multivariate linear regression analysis with
covariates including traditional risk factors, the minor -588T allele
had an independent association with impaired dilation of epicardial
coronary arteries in response to acetylcholine (p less than 0.001), and
it was independently associated with a blunted increase in coronary flow
response to acetylcholine (p less than 0.01). In a subgroup of 59
consecutive patients, constrictor responses to intracoronary infusion of
NG-monomethyl-L-arginine monoacetate, had an inverse and independent
association with the -558T allele in multivariate analysis (p less than
0.01). Nakamura et al. (2003) concluded that the -588T polymorphism
causes a decrease in endothelial nitric oxide bioactivity, leading to
impairment of endothelium-dependent vasomotor function in large and
resistance coronary arteries.
*FIELD* RF
1. Arinami, T.; Ohtsuki, T.; Ishiguro, H.; Ujike, H.; Tanaka, Y.;
Morita, Y.; Mineta, M.; Takeichi, M.; Yamada, S.; Imamura, A.; Ohara,
K.; Shibuya, H.; and 40 others: Genomewide high-density SNP linkage
analysis of 236 Japanese families supports the existence of schizophrenia
susceptibility loci on chromosomes 1p, 14q, and 20p. Am. J. Hum.
Genet. 77: 937-944, 2005.
2. Gipp, J. J.; Bailey, H. H.; Mulcahy, R. T.: 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: 584-589,
1995.
3. Huang, C.-S.; Anderson, M. E.; Meister, A.: Amino acid sequence
and function of the light subunit of rat kidney gamma-glutamylcysteine
synthetase. J. Biol. Chem. 268: 20578-20583, 1993.
4. Nakamura, S.; Kugiyama, K.; Sugiyama, S.; Miyamoto, S.; Koide,
S.; Fukushima, H.; Honda, O.; Yoshimura, M.; Ogawa, H.: Polymorphism
in the 5-prime-flanking region of human glutamate-cysteine ligase
modifier subunit gene is associated with myocardial infarction. Circulation 105:
2968-2973, 2002.
5. Nakamura, S.; Sugiyama, S.; Fujioka, D.; Kawabata, K.; Ogawa, H.;
Kugiyama, K.: Polymorphism in glutamate-cysteine ligase modifier
subunit gene is associated with impairment of nitric oxide-mediated
coronary vasomotor function. Circulation 108: 1425-1427, 2003.
6. Pulver, A. E.; Mulle, J.; Nestadt, G.; Swartz, K. L.; Blouin, J.-L.;
Dombroski, B.; Liang, K.-Y.; Housman, D. E.; Kazazian, H. H.; Antonarakis,
S. E.; Lasseter, V. K.; Wolyniec, P. S.; Thornquist, M. H.; McGrath,
J. A.: Genetic heterogeneity in schizophrenia: stratification of
genome scan data using co-segregating related phenotypes. Molec.
Psychiat. 5: 650-653, 2000.
7. Rozet, J.-M.; Gerber, S.; Perrault, I.; Calvas, P.; Souied, E.;
Chatelin, S.; Viegas-Pequignot, E.; Molina-Gomez, D.; Munnich, A.;
Kaplan, J.: Structure and refinement of the physical mapping of the
gamma-glutamylcysteine ligase regulatory subunit (GLCLR) gene to chromosome
1pp22.1 within the critically deleted region of human malignant mesothelioma. Cytogenet.
Cell Genet. 82: 91-94, 1998.
8. Sierra-Rivera, E.; Dasouki, M.; Summar, M. L.; Krishnamani, M.
R. S.; Meredith, M.; Rao, P. N.; Phillips, J. A., III; Freeman, M.
L.: Assignment of the human gene (GLCLR) that encodes the regulatory
subunit of gamma-glutamylcysteine synthetase to chromosome 1p21. Cytogenet.
Cell Genet. 72: 252-254, 1996.
9. Tosic, M.; Ott, J.; Barral, S.; Bovet, P.; Deppen, P.; Gheorghita,
F.; Matthey, M.-L.; Parnas, J.; Preisig, M.; Saraga, M.; Solida, A.;
Timm, S.; Wang, A. G.; Werge, T.; Cuenod, M.; Do, K. Q.: Schizophrenia
and oxidative stress: glutamate cysteine ligase modifier as a susceptibility
gene. Am. J. Hum. Genet. 79: 586-592, 2006.
10. Tsuchiya, K.; Mulcahy, R. T.; Reid, L. L.; Disteche, C. M.; Kavanagh,
T. J.: 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: 630-632, 1995.
*FIELD* CN
Victor A. McKusick - updated: 8/23/2006
Carol A. Bocchini - updated: 12/9/1998
*FIELD* CD
Alan F. Scott: 4/4/1996
*FIELD* ED
carol: 11/02/2011
ckniffin: 4/8/2011
terry: 9/17/2007
carol: 2/27/2007
alopez: 8/28/2006
terry: 8/23/2006
tkritzer: 9/9/2004
carol: 11/5/2003
carol: 4/17/2002
carol: 11/13/2000
terry: 12/9/1998
dkim: 12/7/1998
carol: 7/30/1998
alopez: 5/13/1997
terry: 6/12/1996
terry: 6/6/1996
mark: 4/4/1996
terry: 4/4/1996
mark: 4/4/1996