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Protein

Glutamate--cysteine ligase catalytic subunit

Gene

GCLC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalytic activityi

ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine.

Activity regulationi

Feedback inhibition by glutathione.

Pathwayi: glutathione biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes glutathione from L-cysteine and L-glutamate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Glutamate--cysteine ligase regulatory subunit (GCLM), Glutamate--cysteine ligase catalytic subunit (GCLC)
  2. Glutathione synthetase (GSS), Glutathione synthetase (HEL-S-64p), Glutathione synthetase, Glutathione synthetase, Glutathione synthetase (GSS)
This subpathway is part of the pathway glutathione biosynthesis, which is itself part of Sulfur metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes glutathione from L-cysteine and L-glutamate, the pathway glutathione biosynthesis and in Sulfur metabolism.

GO - Molecular functioni

  • ADP binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • coenzyme binding Source: UniProtKB
  • glutamate binding Source: UniProtKB
  • glutamate-cysteine ligase activity Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein heterodimerization activity Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processGlutathione biosynthesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000001084-MONOMER
BRENDAi6.3.2.2 2681
ReactomeiR-HSA-174403 Glutathione synthesis and recycling
R-HSA-5578999 Defective GCLC causes Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD)
SIGNORiP48506
UniPathwayi
UPA00142;UER00209

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate--cysteine ligase catalytic subunit (EC:6.3.2.2)
Alternative name(s):
GCS heavy chain
Gamma-ECS
Gamma-glutamylcysteine synthetase
Gene namesi
Name:GCLC
Synonyms:GLCL, GLCLC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000001084.10
HGNCiHGNC:4311 GCLC
MIMi606857 gene+phenotype
neXtProtiNX_P48506

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by hemolytic anemia, glutathione deficiency, myopathy, late-onset spinocerebellar degeneration, and peripheral neuropathy.
See also OMIM:230450
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021110127R → C in HAGGSD. 1 PublicationCorresponds to variant dbSNP:rs760031222Ensembl.1
Natural variantiVAR_015403158P → L in HAGGSD. 1 Publication1
Natural variantiVAR_013514370H → L in HAGGSD. 1 PublicationCorresponds to variant dbSNP:rs121907946EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Hereditary hemolytic anemia

Organism-specific databases

DisGeNETi2729
MalaCardsiGCLC
MIMi230450 phenotype
606857 gene+phenotype
OpenTargetsiENSG00000001084
Orphaneti33574 Glutamate-cysteine ligase deficiency
PharmGKBiPA28612

Chemistry databases

ChEMBLiCHEMBL4055
DrugBankiDB00151 L-Cysteine
DB00142 L-Glutamic Acid
DB00163 Vitamin E

Polymorphism and mutation databases

BioMutaiGCLC
DMDMi1346190

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001925631 – 637Glutamate--cysteine ligase catalytic subunitAdd BLAST637

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei5PhosphoserineCombined sources1
Modified residuei8PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP48506
PaxDbiP48506
PeptideAtlasiP48506
PRIDEiP48506
ProteomicsDBi55896

PTM databases

iPTMnetiP48506
PhosphoSitePlusiP48506

Miscellaneous databases

PMAP-CutDBiP48506

Expressioni

Gene expression databases

BgeeiENSG00000001084 Expressed in 229 organ(s), highest expression level in female gonad
CleanExiHS_GCLC
ExpressionAtlasiP48506 baseline and differential
GenevisibleiP48506 HS

Organism-specific databases

HPAiCAB009569
HPA036359
HPA036360

Interactioni

Subunit structurei

Heterodimer of a catalytic heavy chain and a regulatory light chain.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108991, 11 interactors
IntActiP48506, 2 interactors
STRINGi9606.ENSP00000229416

Chemistry databases

BindingDBiP48506

Structurei

3D structure databases

ProteinModelPortaliP48506
SMRiP48506
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3754 Eukaryota
ENOG410XQIG LUCA
GeneTreeiENSGT00390000011908
HOGENOMiHOG000199354
HOVERGENiHBG005924
InParanoidiP48506
KOiK11204
OMAiPIYRGYL
OrthoDBiEOG091G03DC
PhylomeDBiP48506
TreeFamiTF105644

Family and domain databases

InterProiView protein in InterPro
IPR004308 GCS
IPR014746 Gln_synth/guanido_kin_cat_dom
PANTHERiPTHR11164 PTHR11164, 1 hit
PfamiView protein in Pfam
PF03074 GCS, 1 hit
SUPFAMiSSF55931 SSF55931, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All

P48506-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGLLSQGSPL SWEETKRHAD HVRRHGILQF LHIYHAVKDR HKDVLKWGDE
60 70 80 90 100
VEYMLVSFDH ENKKVRLVLS GEKVLETLQE KGERTNPNHP TLWRPEYGSY
110 120 130 140 150
MIEGTPGQPY GGTMSEFNTV EANMRKRRKE ATSILEENQA LCTITSFPRL
160 170 180 190 200
GCPGFTLPEV KPNPVEGGAS KSLFFPDEAI NKHPRFSTLT RNIRHRRGEK
210 220 230 240 250
VVINVPIFKD KNTPSPFIET FTEDDEASRA SKPDHIYMDA MGFGMGNCCL
260 270 280 290 300
QVTFQACSIS EARYLYDQLA TICPIVMALS AASPFYRGYV SDIDCRWGVI
310 320 330 340 350
SASVDDRTRE ERGLEPLKNN NYRISKSRYD SIDSYLSKCG EKYNDIDLTI
360 370 380 390 400
DKEIYEQLLQ EGIDHLLAQH VAHLFIRDPL TLFEEKIHLD DANESDHFEN
410 420 430 440 450
IQSTNWQTMR FKPPPPNSDI GWRVEFRPME VQLTDFENSA YVVFVVLLTR
460 470 480 490 500
VILSYKLDFL IPLSKVDENM KVAQKRDAVL QGMFYFRKDI CKGGNAVVDG
510 520 530 540 550
CGKAQNSTEL AAEEYTLMSI DTIINGKEGV FPGLIPILNS YLENMEVDVD
560 570 580 590 600
TRCSILNYLK LIKKRASGEL MTVARWMREF IANHPDYKQD SVITDEMNYS
610 620 630
LILKCNQIAN ELCECPELLG SAFRKVKYSG SKTDSSN
Length:637
Mass (Da):72,766
Last modified:January 23, 2007 - v2
Checksum:i511F33F106A15504
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E1CEI4E1CEI4_HUMAN
Glutamate--cysteine ligase catalyti...
GCLC
599Annotation score:
B4E2I4B4E2I4_HUMAN
Glutamate--cysteine ligase catalyti...
GCLC
584Annotation score:
D6RGF8D6RGF8_HUMAN
Glutamate--cysteine ligase catalyti...
GCLC
54Annotation score:
A0A0C4DGB2A0A0C4DGB2_HUMAN
Glutamate--cysteine ligase catalyti...
GCLC
252Annotation score:
A0A2R8Y648A0A2R8Y648_HUMAN
Glutamate--cysteine ligase catalyti...
GCLC
361Annotation score:
A0A2R8YEL6A0A2R8YEL6_HUMAN
Glutamate--cysteine ligase catalyti...
GCLC
639Annotation score:
D6RIT4D6RIT4_HUMAN
Glutamate--cysteine ligase catalyti...
GCLC
18Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01488455L → S. Corresponds to variant dbSNP:rs2066512Ensembl.1
Natural variantiVAR_021110127R → C in HAGGSD. 1 PublicationCorresponds to variant dbSNP:rs760031222Ensembl.1
Natural variantiVAR_015403158P → L in HAGGSD. 1 Publication1
Natural variantiVAR_013514370H → L in HAGGSD. 1 PublicationCorresponds to variant dbSNP:rs121907946EnsemblClinVar.1
Natural variantiVAR_021100462P → S1 PublicationCorresponds to variant dbSNP:rs17883718Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90656 mRNA Translation: AAA58499.1
AY780794 Genomic DNA Translation: AAV31778.1
AL033397 Genomic DNA No translation available.
BC022487 mRNA Translation: AAH22487.1
BC039894 mRNA Translation: AAH39894.1
L39773 Genomic DNA Translation: AAC41751.1
AF118846 Genomic DNA Translation: AAD18031.1
CCDSiCCDS4952.1
PIRiJH0611
RefSeqiNP_001184044.1, NM_001197115.1
NP_001489.1, NM_001498.3
UniGeneiHs.654465

Genome annotation databases

EnsembliENST00000229416; ENSP00000229416; ENSG00000001084
GeneIDi2729
KEGGihsa:2729
UCSCiuc003pbx.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90656 mRNA Translation: AAA58499.1
AY780794 Genomic DNA Translation: AAV31778.1
AL033397 Genomic DNA No translation available.
BC022487 mRNA Translation: AAH22487.1
BC039894 mRNA Translation: AAH39894.1
L39773 Genomic DNA Translation: AAC41751.1
AF118846 Genomic DNA Translation: AAD18031.1
CCDSiCCDS4952.1
PIRiJH0611
RefSeqiNP_001184044.1, NM_001197115.1
NP_001489.1, NM_001498.3
UniGeneiHs.654465

3D structure databases

ProteinModelPortaliP48506
SMRiP48506
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108991, 11 interactors
IntActiP48506, 2 interactors
STRINGi9606.ENSP00000229416

Chemistry databases

BindingDBiP48506
ChEMBLiCHEMBL4055
DrugBankiDB00151 L-Cysteine
DB00142 L-Glutamic Acid
DB00163 Vitamin E

PTM databases

iPTMnetiP48506
PhosphoSitePlusiP48506

Polymorphism and mutation databases

BioMutaiGCLC
DMDMi1346190

Proteomic databases

EPDiP48506
PaxDbiP48506
PeptideAtlasiP48506
PRIDEiP48506
ProteomicsDBi55896

Protocols and materials databases

DNASUi2729
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229416; ENSP00000229416; ENSG00000001084
GeneIDi2729
KEGGihsa:2729
UCSCiuc003pbx.5 human

Organism-specific databases

CTDi2729
DisGeNETi2729
EuPathDBiHostDB:ENSG00000001084.10
GeneCardsiGCLC
HGNCiHGNC:4311 GCLC
HPAiCAB009569
HPA036359
HPA036360
MalaCardsiGCLC
MIMi230450 phenotype
606857 gene+phenotype
neXtProtiNX_P48506
OpenTargetsiENSG00000001084
Orphaneti33574 Glutamate-cysteine ligase deficiency
PharmGKBiPA28612
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3754 Eukaryota
ENOG410XQIG LUCA
GeneTreeiENSGT00390000011908
HOGENOMiHOG000199354
HOVERGENiHBG005924
InParanoidiP48506
KOiK11204
OMAiPIYRGYL
OrthoDBiEOG091G03DC
PhylomeDBiP48506
TreeFamiTF105644

Enzyme and pathway databases

UniPathwayi
UPA00142;UER00209

BioCyciMetaCyc:ENSG00000001084-MONOMER
BRENDAi6.3.2.2 2681
ReactomeiR-HSA-174403 Glutathione synthesis and recycling
R-HSA-5578999 Defective GCLC causes Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD)
SIGNORiP48506

Miscellaneous databases

ChiTaRSiGCLC human
GeneWikiiGCLC
GenomeRNAii2729
PMAP-CutDBiP48506
PROiPR:P48506
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000001084 Expressed in 229 organ(s), highest expression level in female gonad
CleanExiHS_GCLC
ExpressionAtlasiP48506 baseline and differential
GenevisibleiP48506 HS

Family and domain databases

InterProiView protein in InterPro
IPR004308 GCS
IPR014746 Gln_synth/guanido_kin_cat_dom
PANTHERiPTHR11164 PTHR11164, 1 hit
PfamiView protein in Pfam
PF03074 GCS, 1 hit
SUPFAMiSSF55931 SSF55931, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGSH1_HUMAN
AccessioniPrimary (citable) accession number: P48506
Secondary accession number(s): Q14399
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 168 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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