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GCLC glutamate-cysteine ligase catalytic subunit [ Homo sapiens (human) ]

Gene ID: 2729, updated on 12-Jan-2019

Summary

Official Symbol
GCLCprovided by HGNC
Official Full Name
glutamate-cysteine ligase catalytic subunitprovided by HGNC
Primary source
HGNC:HGNC:4311
See related
Ensembl:ENSG00000001084 MIM:606857
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GCL; GCS; GLCL; GLCLC
Summary
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. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.[provided by RefSeq, Oct 2010]
Expression
Ubiquitous expression in liver (RPKM 39.8), urinary bladder (RPKM 19.1) and 24 other tissues See more
Orthologs

Genomic context

See GCLC in Genome Data Viewer
Location:
6p12.1
Exon count:
16
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 6 NC_000006.12 (53497341..53545129, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (53362139..53409927, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene RNA, 7SK small nuclear pseudogene 256 Neighboring gene Nanog homeobox pseudogene 3 Neighboring gene uncharacterized LOC105375095 Neighboring gene uncharacterized LOC101927136 Neighboring gene long intergenic non-protein coding RNA 1564

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Pathways from BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ADP binding IDA
Inferred from Direct Assay
more info
PubMed 
ATP binding IEA
Inferred from Electronic Annotation
more info
 
coenzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
glutamate binding IDA
Inferred from Direct Assay
more info
PubMed 
glutamate-cysteine ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutamate-cysteine ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
glutamate-cysteine ligase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
magnesium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
protein heterodimerization activity IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
L-ascorbic acid metabolic process IEA
Inferred from Electronic Annotation
more info
 
aging IEA
Inferred from Electronic Annotation
more info
 
apoptotic mitochondrial changes IEA
Inferred from Electronic Annotation
more info
 
cell redox homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to fibroblast growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to follicle-stimulating hormone stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to hepatocyte growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to insulin stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to mechanical stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to thyroxine stimulus IEA
Inferred from Electronic Annotation
more info
 
cysteine metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
glutamate metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
glutathione biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutathione biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
glutathione biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
glutathione biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of extrinsic apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of hepatic stellate cell activation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein ubiquitination IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of proteasomal ubiquitin-dependent protein catabolic process IEA
Inferred from Electronic Annotation
more info
 
regulation of blood vessel size IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of mitochondrial depolarization IEA
Inferred from Electronic Annotation
more info
 
response to activity IEA
Inferred from Electronic Annotation
more info
 
response to arsenic-containing substance IEA
Inferred from Electronic Annotation
more info
 
response to cadmium ion IEA
Inferred from Electronic Annotation
more info
 
response to heat IDA
Inferred from Direct Assay
more info
PubMed 
response to hormone IDA
Inferred from Direct Assay
more info
PubMed 
response to human chorionic gonadotropin IEA
Inferred from Electronic Annotation
more info
 
response to interleukin-1 IEA
Inferred from Electronic Annotation
more info
 
response to nitrosative stress IEA
Inferred from Electronic Annotation
more info
 
response to nutrient IEA
Inferred from Electronic Annotation
more info
 
response to oxidative stress IDA
Inferred from Direct Assay
more info
PubMed 
response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol TAS
Traceable Author Statement
more info
 
glutamate-cysteine ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutamate-cysteine ligase complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
glutamate--cysteine ligase catalytic subunit
Names
GCS heavy chain
gamma-ECS
gamma-glutamylcysteine synthetase
NP_001184044.1
NP_001489.1
XP_016866238.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012071.2 RefSeqGene

    Range
    5029..52789
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1166

mRNA and Protein(s)

  1. NM_001197115.1NP_001184044.1  glutamate--cysteine ligase catalytic subunit isoform b

    See identical proteins and their annotated locations for NP_001184044.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also referred to as delta4) lacks an in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform b), compared to isoform a.
    Source sequence(s)
    AB262176, AB516284, AK313480, AL531593, BC039894, BI550814
    Consensus CDS
    CCDS75471.1
    UniProtKB/Swiss-Prot
    P48506
    UniProtKB/TrEMBL
    E1CEI4, Q14TF0
    Related
    ENSP00000424211.2, ENST00000513939.6
    Conserved Domains (1) summary
    pfam03074
    Location:198570
    GCS; Glutamate-cysteine ligase
  2. NM_001498.4NP_001489.1  glutamate--cysteine ligase catalytic subunit isoform a

    See identical proteins and their annotated locations for NP_001489.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    AB262176, AK313480, AL531593, BC039894, BI550814
    Consensus CDS
    CCDS4952.1
    UniProtKB/Swiss-Prot
    P48506
    UniProtKB/TrEMBL
    Q14TF0
    Related
    ENSP00000229416.6, ENST00000229416.10
    Conserved Domains (2) summary
    pfam03074
    Location:236608
    GCS; Glutamate-cysteine ligase
    cl28253
    Location:2276
    RpsA; Ribosomal protein S1 [Translation, ribosomal structure and biogenesis]

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p12 Primary Assembly

    Range
    53497341..53545129 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017010749.1XP_016866238.1  glutamate--cysteine ligase catalytic subunit isoform X1

    Related
    ENSP00000495056.1, ENST00000509541.5
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