GCLC

Glutamate—cysteine ligase catalytic subunit is an enzyme that in humans is encoded by the GCLC gene.[5][6]

GCLC
Identifiers
AliasesGCLC, GCL, GCS, GLCL, GLCLC, glutamate-cysteine ligase catalytic subunit
External IDsOMIM: 606857 MGI: 104990 HomoloGene: 1148 GeneCards: GCLC
Orthologs
SpeciesHumanMouse
Entrez

2729

14629

Ensembl

ENSG00000001084

ENSMUSG00000032350

UniProt

P48506

P97494

RefSeq (mRNA)

NM_001498
NM_001197115

NM_010295

RefSeq (protein)

NP_001184044
NP_001489

NP_034425

Location (UCSC)Chr 6: 53.5 – 53.62 MbChr 9: 77.66 – 77.7 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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. The gene encoding the catalytic subunit encodes a protein of 367 amino acids with a calculated molecular weight of 72.773 kDa and maps to chromosome 6. The regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Deficiency of gamma-glutamylcysteine synthetase in human is associated with enzymopathic hemolytic anemia.[6]

Model organisms

Model organisms have been used in the study of GCLC function. A conditional knockout mouse line, called Gclctm1a(EUCOMM)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty four tests were carried out on mutant mice, however no significant abnormalities were observed.[9]

References

  1. GRCh38: Ensembl release 89: ENSG00000001084 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000032350 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Gipp JJ, Chang C, Mulcahy RT (May 1992). "Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase". Biochemical and Biophysical Research Communications. 185 (1): 29–35. doi:10.1016/S0006-291X(05)80950-7. PMID 1350904.
  6. "Entrez Gene: GCLC glutamate-cysteine ligase, catalytic subunit".
  7. "Salmonella infection data for Gclc". Wellcome Trust Sanger Institute.
  8. "Citrobacter infection data for Gclc". Wellcome Trust Sanger Institute.
  9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  10. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. "International Knockout Mouse Consortium".
  12. "Mouse Genome Informatics".
  13. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  14. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  15. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  16. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

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