GSH1_RAT
ID GSH1_RAT Reviewed; 637 AA.
AC P19468;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Glutamate--cysteine ligase catalytic subunit;
DE EC=6.3.2.2;
DE AltName: Full=GCS heavy chain;
DE AltName: Full=Gamma-ECS;
DE AltName: Full=Gamma-glutamylcysteine synthetase;
GN Name=Gclc; Synonyms=Glclc;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Kidney;
RX PubMed=1967255; DOI=10.1016/s0021-9258(19)40057-4;
RA Yan N., Meister A.;
RT "Amino acid sequence of rat kidney gamma-glutamylcysteine synthetase.";
RL J. Biol. Chem. 265:1588-1593(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5 AND SER-8, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-cysteine + L-glutamate = ADP + gamma-L-glutamyl-L-
CC cysteine + H(+) + phosphate; Xref=Rhea:RHEA:13285, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:35235,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58173, ChEBI:CHEBI:456216; EC=6.3.2.2;
CC -!- ACTIVITY REGULATION: Feedback inhibition by glutathione.
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 -!- TISSUE SPECIFICITY: Most abundant in kidney. Also found in liver and
CC testis.
CC -!- SIMILARITY: Belongs to the glutamate--cysteine ligase type 3 family.
CC {ECO:0000305}.
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DR EMBL; J05181; AAA41208.1; -; mRNA.
DR EMBL; BC081702; AAH81702.1; -; mRNA.
DR PIR; A35015; A35015.
DR RefSeq; NP_036947.1; NM_012815.2.
DR AlphaFoldDB; P19468; -.
DR SMR; P19468; -.
DR BioGRID; 247323; 1.
DR CORUM; P19468; -.
DR STRING; 10116.ENSRNOP00000035540; -.
DR BindingDB; P19468; -.
DR ChEMBL; CHEMBL2366469; -.
DR iPTMnet; P19468; -.
DR PhosphoSitePlus; P19468; -.
DR jPOST; P19468; -.
DR PaxDb; P19468; -.
DR PRIDE; P19468; -.
DR Ensembl; ENSRNOT00000033196; ENSRNOP00000035540; ENSRNOG00000006302.
DR GeneID; 25283; -.
DR KEGG; rno:25283; -.
DR UCSC; RGD:619868; rat.
DR CTD; 2729; -.
DR RGD; 619868; Gclc.
DR eggNOG; KOG3754; Eukaryota.
DR GeneTree; ENSGT00390000011908; -.
DR HOGENOM; CLU_010467_0_0_1; -.
DR InParanoid; P19468; -.
DR OMA; YISQDPR; -.
DR OrthoDB; 575052at2759; -.
DR PhylomeDB; P19468; -.
DR TreeFam; TF105644; -.
DR BioCyc; MetaCyc:MON-10024; -.
DR BRENDA; 6.3.2.2; 5301.
DR Reactome; R-RNO-174403; Glutathione synthesis and recycling.
DR SABIO-RK; P19468; -.
DR UniPathway; UPA00142; UER00209.
DR PRO; PR:P19468; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000006302; Expressed in kidney and 20 other tissues.
DR Genevisible; P19468; RN.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0017109; C:glutamate-cysteine ligase complex; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016595; F:glutamate binding; ISS:UniProtKB.
DR GO; GO:0004357; F:glutamate-cysteine ligase activity; IDA:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISS:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0097069; P:cellular response to thyroxine stimulus; IEP:RGD.
DR GO; GO:0006534; P:cysteine metabolic process; ISS:UniProtKB.
DR GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; IMP:RGD.
DR GO; GO:0006749; P:glutathione metabolic process; ISO:RGD.
DR GO; GO:0019852; P:L-ascorbic acid metabolic process; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:2000490; P:negative regulation of hepatic stellate cell activation; IMP:RGD.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0051900; P:regulation of mitochondrial depolarization; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0046685; P:response to arsenic-containing substance; ISO:RGD.
DR GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
DR GO; GO:0009408; P:response to heat; ISS:UniProtKB.
DR GO; GO:0009725; P:response to hormone; ISS:UniProtKB.
DR GO; GO:0044752; P:response to human chorionic gonadotropin; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; IEP:RGD.
DR GO; GO:0051409; P:response to nitrosative stress; IMP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IMP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR InterPro; IPR004308; GCS.
DR InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR PANTHER; PTHR11164; PTHR11164; 1.
DR Pfam; PF03074; GCS; 1.
DR SUPFAM; SSF55931; SSF55931; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Direct protein sequencing;
KW Glutathione biosynthesis; Ligase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..637
FT /note="Glutamate--cysteine ligase catalytic subunit"
FT /id="PRO_0000192565"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P48506"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 637 AA; 72619 MW; 9F0AFA15684A5AE2 CRC64;
MGLLSQGSPL SWEETQRHAD HVRRHGILQF LHIYHAVKDR HKDVLKWGDE VEYMLVSFDH
ENRKVQLLLN GGDVLETLQE KGERTNPNHP TLWRPEYGSY MIEGTPGQPY GGTMSEFNTV
EDNMRKRRKE ATSVLGEHQA LCTITSFPRL GCPGFTLPEH RPNPEEGGAS KSLFFPDEAI
NKHPRFGTLT RNIRHRRGEK VVINVPIFKD KNTPSPFVET FPEDEEASKA SKPDHIYMDA
MGFGMGNCCL QVTFQACSIS EARYLYDQLA TICPIVMALS AASPFYRGYV SDIDCRWGVI
SASVDDRTRE ERGLEPLKNN RFKISKSRYD SIDSYLSKCG EKYNDIDLTI DTEIYEQLLE
EGIDHLLAQH VAHLFIRDPL TLFEEKIHLD DANESDHFEN IQSTNWQTMR FKPPPPNSDI
GWRVEFRPME VQLTDFENSA YVVFVVLLTR VILSYKLDFL IPLSKVDENM KVAQERDAVL
QGMFYFRKDI CKGGNAVVDG CSKAQTSSEP SAEEYTLMSI DTIINGKEGV FPGLIPILNS
YLENMEVDVD TRCSILNYLK LIKKRASGEL MTVARWMREF IANHPDYKQD SVITDEINYS
LILKCNQIAN ELCECPELLG SGFRKAKYSG GKSDPSD
