ID   GSH0_HUMAN              Reviewed;         274 AA.
AC   P48507; A8K334; D3DT45; M5A959; Q6FHC1; Q9NPX9; Q9NU74;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 198.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 liver
RT   gamma-glutamylcysteine synthetase and relative mRNA levels for heavy and
RT   light subunits in human normal tissues.";
RL   Biochem. Biophys. Res. Commun. 206:584-589(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RA   Sawada Y., Sudo M., Fujii A., Mizuochi A., Hisatomi H.;
RT   "Homo sapiens GCLM mRNA for glutamate-cysteine ligase, modifier subunit
RT   delta2 alternative splicing variant, complete cds.";
RL   Submitted (MAR-2013) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-209.
RG   NIEHS SNPs program;
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., 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., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   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   [6]
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., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., 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., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., 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., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., 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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-263, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   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   [10]
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., Buerckstuemmer T.,
RA   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 from
CC       L-cysteine and L-glutamate: step 1/2.
CC   -!- SUBUNIT: Heterodimer of a catalytic heavy chain and a regulatory light
CC       chain.
CC   -!- INTERACTION:
CC       P48507; P48506: GCLC; NbExp=2; IntAct=EBI-1051387, EBI-2832840;
CC       P48507; Q9UJX0: OSGIN1; NbExp=3; IntAct=EBI-1051387, EBI-9057006;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P48507-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P48507-2; Sequence=VSP_057008;
CC   -!- TISSUE SPECIFICITY: In all tissues examined. Highest levels in skeletal
CC       muscle.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family.
CC       Glutamate--cysteine ligase light chain subfamily. {ECO:0000305}.
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; AB809606; BAN05309.1; -; mRNA.
DR   EMBL; CR541833; CAG46632.1; -; mRNA.
DR   EMBL; AY773965; AAV28733.1; -; Genomic_DNA.
DR   EMBL; AK290449; BAF83138.1; -; mRNA.
DR   EMBL; AL049796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL117351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471097; EAW73060.1; -; Genomic_DNA.
DR   EMBL; CH471097; EAW73061.1; -; Genomic_DNA.
DR   EMBL; BC041809; AAH41809.1; -; mRNA.
DR   CCDS; CCDS746.1; -. [P48507-1]
DR   CCDS; CCDS81352.1; -. [P48507-2]
DR   PIR; JC2474; JC2474.
DR   RefSeq; NP_001295182.1; NM_001308253.1. [P48507-2]
DR   RefSeq; NP_002052.1; NM_002061.3. [P48507-1]
DR   AlphaFoldDB; P48507; -.
DR   SMR; P48507; -.
DR   BioGRID; 108992; 54.
DR   ComplexPortal; CPX-2865; Glutamate-cysteine ligase complex.
DR   CORUM; P48507; -.
DR   IntAct; P48507; 18.
DR   MINT; P48507; -.
DR   STRING; 9606.ENSP00000359258; -.
DR   ChEMBL; CHEMBL4295765; -.
DR   DrugBank; DB00151; Cysteine.
DR   DrugBank; DB00142; Glutamic acid.
DR   GlyGen; P48507; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P48507; -.
DR   PhosphoSitePlus; P48507; -.
DR   BioMuta; GCLM; -.
DR   DMDM; 1346188; -.
DR   OGP; P48507; -.
DR   EPD; P48507; -.
DR   jPOST; P48507; -.
DR   MassIVE; P48507; -.
DR   MaxQB; P48507; -.
DR   PaxDb; 9606-ENSP00000359258; -.
DR   PeptideAtlas; P48507; -.
DR   ProteomicsDB; 55897; -. [P48507-1]
DR   Pumba; P48507; -.
DR   Antibodypedia; 4034; 540 antibodies from 36 providers.
DR   CPTC; P48507; 3 antibodies.
DR   DNASU; 2730; -.
DR   Ensembl; ENST00000370238.8; ENSP00000359258.3; ENSG00000023909.10. [P48507-1]
DR   Ensembl; ENST00000615724.1; ENSP00000484507.1; ENSG00000023909.10. [P48507-2]
DR   GeneID; 2730; -.
DR   KEGG; hsa:2730; -.
DR   MANE-Select; ENST00000370238.8; ENSP00000359258.3; NM_002061.4; NP_002052.1.
DR   UCSC; uc001dqg.2; human. [P48507-1]
DR   AGR; HGNC:4312; -.
DR   CTD; 2730; -.
DR   DisGeNET; 2730; -.
DR   GeneCards; GCLM; -.
DR   HGNC; HGNC:4312; GCLM.
DR   HPA; ENSG00000023909; Tissue enhanced (liver).
DR   MalaCards; GCLM; -.
DR   MIM; 601176; gene+phenotype.
DR   neXtProt; NX_P48507; -.
DR   OpenTargets; ENSG00000023909; -.
DR   PharmGKB; PA28613; -.
DR   VEuPathDB; HostDB:ENSG00000023909; -.
DR   eggNOG; KOG3023; Eukaryota.
DR   GeneTree; ENSGT00510000047658; -.
DR   HOGENOM; CLU_055657_1_0_1; -.
DR   InParanoid; P48507; -.
DR   OMA; AHEWIPL; -.
DR   OrthoDB; 1706825at2759; -.
DR   PhylomeDB; P48507; -.
DR   TreeFam; TF105986; -.
DR   BioCyc; MetaCyc:ENSG00000023909-MONOMER; -.
DR   BRENDA; 6.3.2.2; 2681.
DR   PathwayCommons; P48507; -.
DR   Reactome; R-HSA-174403; Glutathione synthesis and recycling.
DR   Reactome; R-HSA-5578999; Defective GCLC causes HAGGSD.
DR   Reactome; R-HSA-9818027; NFE2L2 regulating anti-oxidant/detoxification enzymes.
DR   SignaLink; P48507; -.
DR   UniPathway; UPA00142; UER00209.
DR   BioGRID-ORCS; 2730; 13 hits in 1160 CRISPR screens.
DR   ChiTaRS; GCLM; human.
DR   GeneWiki; GCLM; -.
DR   GenomeRNAi; 2730; -.
DR   Pharos; P48507; Tbio.
DR   PRO; PR:P48507; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P48507; Protein.
DR   Bgee; ENSG00000023909; Expressed in bronchial epithelial cell and 204 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0017109; C:glutamate-cysteine ligase complex; IDA:UniProtKB.
DR   GO; GO:0030234; F:enzyme regulator activity; IBA:GO_Central.
DR   GO; GO:0004357; F:glutamate-cysteine ligase activity; IEA:Ensembl.
DR   GO; GO:0035226; F:glutamate-cysteine ligase catalytic subunit binding; IPI:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR   GO; GO:0008637; P:apoptotic mitochondrial changes; IEA:Ensembl.
DR   GO; GO:0097746; P:blood vessel diameter maintenance; IMP:UniProtKB.
DR   GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl.
DR   GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR   GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEA:Ensembl.
DR   GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR   GO; GO:0097069; P:cellular response to thyroxine stimulus; 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:0035733; P:hepatic stellate cell activation; IEA:Ensembl.
DR   GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0051900; P:regulation of mitochondrial depolarization; IEA:Ensembl.
DR   GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR   GO; GO:0044752; P:response to human chorionic gonadotropin; IEA:Ensembl.
DR   GO; GO:0051409; P:response to nitrosative stress; IEA:Ensembl.
DR   GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR   GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB.
DR   Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1.
DR   InterPro; IPR032963; Gclm.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   PANTHER; PTHR13295; GLUTAMATE CYSTEINE LIGASE REGULATORY SUBUNIT; 1.
DR   PANTHER; PTHR13295:SF4; GLUTAMATE--CYSTEINE LIGASE REGULATORY SUBUNIT; 1.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1.
DR   Genevisible; P48507; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Glutathione biosynthesis;
KW   Reference proteome.
FT   CHAIN           1..274
FT                   /note="Glutamate--cysteine ligase regulatory subunit"
FT                   /id="PRO_0000192573"
FT   MOD_RES         263
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   VAR_SEQ         43..64
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_057008"
FT   VARIANT         209
FT                   /note="I -> M (in dbSNP:rs17880087)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="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
//