Gclc Glutamate-cysteine ligase catalytic subunit [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Gclcprovided by FlyBase
Official Full Name: Glutamate-cysteine ligase catalytic subunitprovided by FlyBase
Primary source: FLYBASE:FBgn0040319
Locus tag: Dmel_CG2259
See related: AllianceGenome:FB:FBgn0040319
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: 2259; CG2259; Dmel\CG2259; DmGCLC; DmGCS; DmGCSh; GCL; gclc; gclC; GclC; GCLc; GCLC; Gcs; Gcsh; GCSh; mTOR
Summary: Enables glutamate-cysteine ligase activity. Involved in several processes, including glutathione biosynthetic process; imaginal disc-derived wing morphogenesis; and response to copper ion. Located in nucleus and perinuclear region of cytoplasm. Part of glutamate-cysteine ligase complex. Is expressed in embryonic/larval midgut; organism; and posterior midgut primordium. Human ortholog(s) of this gene implicated in cystic fibrosis; glutamate-cysteine ligase deficiency; hemolytic anemia; and myocardial infarction. Orthologous to human GCLC (glutamate-cysteine ligase catalytic subunit). [provided by Alliance of Genome Resources, Jan 2025]
Orthologs: all
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Genomic context

Location:: 7D6-7D6; 1-22 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	X	NC_004354.4 (8102181..8116147, complement)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	X	NC_004354.3 (7996214..8010180, complement)

Chromosome X - NC_004354.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

we report phenotypic analysis of a complete loss-of-function mutant in the gamma-glutamylcysteine synthetase catalytic subunit (Gclc) gene in the fruit fly Drosophila melanogaster.Gclc encodes the evolutionarily conserved catalytic component of the enzyme that conjugates glutamate and cysteine in the GSH biosynthesis pathway.
Title: Dual Roles of Glutathione in Ecdysone Biosynthesis and Antioxidant Function During Larval Development in Drosophila.
Microarray analysis revealed that glutamate cysteine ligasec overexpression and thus enhanced glutathione production has a broad impact on gene expression that largely affects different processes in young and old flies.
Title: Age-dependent changes in the transcription profile of long-lived Drosophila over-expressing glutamate cysteine ligase.
GSH biosynthesis in the nucleus is associated with migration of only the GCLc subunit from the cytoplasm into the nucleus, and this migration requires the presence of an intact nuclear localization signal
Title: The catalytic subunit of Drosophila glutamate-cysteine ligase is a nucleocytoplasmic shuttling protein.
that the longevity effects of GCLc are dependent on dosage and that there are specific tissues (mushroom bodies, motor neurons, and transverse muscle cells) particularly sensitive to the benefits of GCLc overexpression.
Title: Modulating longevity in Drosophila by over- and underexpression of glutamate-cysteine ligase.
The reversibility of the dephosphorylation-dependent activation was indicated by the time-dependent inactivation of the in vitro activated Drosophila GCL, by preincubation with MgATP.
Title: Mechanisms of gamma-glutamylcysteine ligase regulation.
Neuronal overexpression of GCLc in a long-lived background extended mean and maximum life spans up to 50%, without affecting the rate of oxygen consumption by the flies
Title: Overexpression of glutamate-cysteine ligase extends life span in Drosophila melanogaster.
investigation of mutations in GCL modifier subunit and the GCL catalytic subunit that modify catalytic activity and lower glutathione levels
Title: The modifier subunit of Drosophila glutamate-cysteine ligase regulates catalytic activity by covalent and noncovalent interactions and influences glutathione homeostasis in vivo.

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Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Dm1849 (e-PCR)
- UniSTS:55224

Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
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	IEA Inferred from Electronic Annotation more info
enables glutamate-cysteine ligase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables glutamate-cysteine ligase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in axonogenesis	IMP Inferred from Mutant Phenotype 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	IGI Inferred from Genetic Interaction more info	PubMed
involved_in glutathione biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in glutathione metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in imaginal disc-derived wing morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to copper ion	IDA Inferred from Direct Assay more info	PubMed
involved_in response to copper ion	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
part_of glutamate-cysteine ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of glutamate-cysteine ligase complex	IPI Inferred from Physical Interaction more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: Glutamate-cysteine ligase catalytic subunit

Names: CG2259-PA; CG2259-PB; CG2259-PC; CG2259-PD; Gclc-PA; Gclc-PB; Gclc-PC; Gclc-PD; catalytic subunit of glutamate- cysteine ligase; gamma-Glutamylcysteine synthetase; gamma-Glutamylcysteine synthetase catalytic subunit; gamma-glutamylcysteine ligase; glutamate cysteine ligase; glutamate-cysteine ligase

NP_001285001.1

EC 6.3.2.2

NP_001285002.1

EC 6.3.2.2

NP_525005.2

EC 6.3.2.2

NP_996373.1

EC 6.3.2.2

NCBI Reference Sequences (RefSeq)

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Genome Annotation

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

Reference assembly

Genomic

NC_004354.4 Reference assembly

Range

8102181..8116147 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001298072.1 → NP_001285001.1 Glutamate-cysteine ligase catalytic subunit, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001285001.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9NGQ3, Q9W3K5

UniProtKB/TrEMBL

A4V448

Conserved Domains (1) summary

pfam03074
Location:232 → 675

GCS; Glutamate-cysteine ligase
NM_080266.3 → NP_525005.2 Glutamate-cysteine ligase catalytic subunit, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_525005.2

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9NGQ3, Q9W3K5

UniProtKB/TrEMBL

A4V448

Related

FBpp0071063

Conserved Domains (1) summary

pfam03074
Location:232 → 675

GCS; Glutamate-cysteine ligase
NM_001298073.1 → NP_001285002.1 Glutamate-cysteine ligase catalytic subunit, isoform D [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001285002.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9NGQ3, Q9W3K5

UniProtKB/TrEMBL

A4V448

Conserved Domains (1) summary

pfam03074
Location:232 → 675

GCS; Glutamate-cysteine ligase
NM_206650.2 → NP_996373.1 Glutamate-cysteine ligase catalytic subunit, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_996373.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9NGQ3, Q9W3K5

UniProtKB/TrEMBL

A4V448

Conserved Domains (1) summary

pfam03074
Location:232 → 675

GCS; Glutamate-cysteine ligase