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

    Gene ID: 2729, updated on 17-Jun-2024

    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; AllianceGenome:HGNC:4311
    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
    NEW
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    Try the new Transcript table

    Genomic context

    See GCLC in Genome Data Viewer
    Location:
    6p12.1
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (53497341..53545101, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (53337262..53388129, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (53362139..53409899, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene RN7SK pseudogene 256 Neighboring gene Nanog homeobox pseudogene 3 Neighboring gene GCLC antisense RNA 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:53407007-53407644 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:53408583-53409324 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17291 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17292 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:53437832-53438332 Neighboring gene KRT19 interacting long noncoding RNA in hepatocellular carcinoma Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:53480209-53481408 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 Functions

    What's a GeneRIF?

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

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

    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_054211163.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_001197115.2NP_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/TrEMBL
      A0A2R8YEL6, E1CEI4, H0Y9I7
      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, Q14399
      UniProtKB/TrEMBL
      A0A2R8YEL6, Q14TF0
      Related
      ENSP00000497574.1, ENST00000650454.1
      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: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      53497341..53545101 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      53337262..53388129 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355188.1XP_054211163.1  glutamate--cysteine ligase catalytic subunit isoform X1

      UniProtKB/Swiss-Prot
      P48506, Q14399
      UniProtKB/TrEMBL
      A0A2R8YEL6, Q14TF0