• Gene id: 2729

Gene Summary

• Gene Symbol: GCLC   Gene   UCSC   Ensembl
• Aliases: GCL, GCS, GLCL, GLCLC
• Gene name: glutamate-cysteine ligase catalytic subunit
• Alternate names: glutamate--cysteine ligase catalytic subunit, GCS heavy chain, gamma-ECS, gamma-glutamylcysteine synthetase,
• Gene location: 6p12.1 (43517023: 43562406)     Exons: 12     NC_000006.12
• Gene summary(Entrez): 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 ca
• OMIM: 606857

Protein Summary

• Protein general information: P48506  
  • Name: Glutamate cysteine ligase catalytic subunit (EC 6.3.2.2) (GCS heavy chain) (Gamma ECS) (Gamma glutamylcysteine synthetase)
  • Length: 637  
  • Mass: 72766
• Sequence:

  MGLLSQGSPLSWEETKRHADHVRRHGILQFLHIYHAVKDRHKDVLKWGDEVEYMLVSFDHENKKVRLVLSGEKVL
  ETLQEKGERTNPNHPTLWRPEYGSYMIEGTPGQPYGGTMSEFNTVEANMRKRRKEATSILEENQALCTITSFPRL
  GCPGFTLPEVKPNPVEGGASKSLFFPDEAINKHPRFSTLTRNIRHRRGEKVVINVPIFKDKNTPSPFIETFTEDD
  EASRASKPDHIYMDAMGFGMGNCCLQVTFQACSISEARYLYDQLATICPIVMALSAASPFYRGYVSDIDCRWGVI
  SASVDDRTREERGLEPLKNNNYRISKSRYDSIDSYLSKCGEKYNDIDLTIDKEIYEQLLQEGIDHLLAQHVAHLF
  IRDPLTLFEEKIHLDDANESDHFENIQSTNWQTMRFKPPPPNSDIGWRVEFRPMEVQLTDFENSAYVVFVVLLTR
  VILSYKLDFLIPLSKVDENMKVAQKRDAVLQGMFYFRKDICKGGNAVVDGCGKAQNSTELAAEEYTLMSIDTIIN
  GKEGVFPGLIPILNSYLENMEVDVDTRCSILNYLKLIKKRASGELMTVARWMREFIANHPDYKQDSVITDEMNYS
  LILKCNQIANELCECPELLGSAFRKVKYSGSKTDSSN

• Structural information:
  • Interpro: IPR004308  IPR014746  
  • STRING: ENSP00000229416
• Other Databases: GeneCards:  GCLC  Malacards:  GCLC

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0006750	glutathione biosynthetic process	IBA	biological process
GO:0004357	glutamate-cysteine ligase activity	IBA	molecular function
GO:0017109	glutamate-cysteine ligase complex	IBA	cellular component
GO:0006750	glutathione biosynthetic process	IEA	biological process
GO:0003824	catalytic activity	IEA	molecular function
GO:0004357	glutamate-cysteine ligase activity	IEA	molecular function
GO:0006750	glutathione biosynthetic process	IEA	biological process
GO:0000166	nucleotide binding	IEA	molecular function
GO:0016874	ligase activity	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0004357	glutamate-cysteine ligase activity	IEA	molecular function
GO:0005829	cytosol	TAS	cellular component
GO:0006750	glutathione biosynthetic process	TAS	biological process
GO:1901029	negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	IEA	biological process
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA	biological process
GO:0031397	negative regulation of protein ubiquitination	IEA	biological process
GO:0019852	L-ascorbic acid metabolic process	IEA	biological process
GO:0006750	glutathione biosynthetic process	IEA	biological process
GO:0005829	cytosol	IEA	cellular component
GO:0071372	cellular response to follicle-stimulating hormone stimulus	IEA	biological process
GO:0071333	cellular response to glucose stimulus	IEA	biological process
GO:0070555	response to interleukin-1	IEA	biological process
GO:0051409	response to nitrosative stress	IEA	biological process
GO:0046686	response to cadmium ion	IEA	biological process
GO:0044752	response to human chorionic gonadotropin	IEA	biological process
GO:0044344	cellular response to fibroblast growth factor stimulus	IEA	biological process
GO:0035729	cellular response to hepatocyte growth factor stimulus	IEA	biological process
GO:0032869	cellular response to insulin stimulus	IEA	biological process
GO:0014823	response to activity	IEA	biological process
GO:0007584	response to nutrient	IEA	biological process
GO:0007568	aging	IEA	biological process
GO:0006750	glutathione biosynthetic process	IEA	biological process
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway	IEA	biological process
GO:0051900	regulation of mitochondrial depolarization	IEA	biological process
GO:0046685	response to arsenic-containing substance	IEA	biological process
GO:0017109	glutamate-cysteine ligase complex	IEA	cellular component
GO:0009410	response to xenobiotic stimulus	IEA	biological process
GO:0006749	glutathione metabolic process	IEA	biological process
GO:0004357	glutamate-cysteine ligase activity	IEA	molecular function
GO:2000490	negative regulation of hepatic stellate cell activation	IEA	biological process
GO:0097069	cellular response to thyroxine stimulus	IEA	biological process
GO:0071260	cellular response to mechanical stimulus	IEA	biological process
GO:0044877	protein-containing complex binding	IEA	molecular function
GO:0043524	negative regulation of neuron apoptotic process	IEA	biological process
GO:0017109	glutamate-cysteine ligase complex	IEA	cellular component
GO:0006979	response to oxidative stress	IEA	biological process
GO:0004357	glutamate-cysteine ligase activity	IEA	molecular function
GO:0005739	mitochondrion	IEA	cellular component
GO:0006750	glutathione biosynthetic process	IEA	biological process
GO:0006750	glutathione biosynthetic process	IDA	biological process
GO:0016595	glutamate binding	IDA	molecular function
GO:0009408	response to heat	IDA	biological process
GO:0006750	glutathione biosynthetic process	IDA	biological process
GO:0006750	glutathione biosynthetic process	IDA	biological process
GO:0006536	glutamate metabolic process	IDA	biological process
GO:0045454	cell redox homeostasis	IDA	biological process
GO:0009725	response to hormone	IDA	biological process
GO:0006536	glutamate metabolic process	IDA	biological process
GO:0006536	glutamate metabolic process	IDA	biological process
GO:0004357	glutamate-cysteine ligase activity	IDA	molecular function
GO:0017109	glutamate-cysteine ligase complex	IDA	cellular component
GO:0017109	glutamate-cysteine ligase complex	IDA	cellular component
GO:0004357	glutamate-cysteine ligase activity	IDA	molecular function
GO:0043531	ADP binding	IDA	molecular function
GO:0006979	response to oxidative stress	IDA	biological process
GO:0006979	response to oxidative stress	IDA	biological process
GO:0004357	glutamate-cysteine ligase activity	IDA	molecular function
GO:0045892	negative regulation of transcription, DNA-templated	IDA	biological process
GO:0043066	negative regulation of apoptotic process	IDA	biological process
GO:0006534	cysteine metabolic process	IDA	biological process
GO:0000287	magnesium ion binding	IDA	molecular function
GO:0006750	glutathione biosynthetic process	IMP	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0004357	glutamate-cysteine ligase activity	IMP	molecular function
GO:0097746	regulation of blood vessel diameter	IMP	biological process
GO:0004357	glutamate-cysteine ligase activity	IMP	molecular function

KEGG pathways

Pathway id	Pathway name
hsa01100	Metabolic pathways
hsa00270	Cysteine and methionine metabolism
hsa00480	Glutathione metabolism
hsa04216	Ferroptosis

Diseases

Associated diseases	References
Anemia due to disorders of glutathione metabolism	KEGG:H00668
Anemia due to disorders of glutathione metabolism	KEGG:H00668
Cystic fibrosis	PMID:16690975
Hemolytic anemia	PMID:10733484
Myocardial infarction	PMID:12598062
colorectal cancer	PMID:8705999
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
17327269	Teratozoospermia			13 (5 controls, 8 cases)	Male infertility	GSE6967 analyzed by GEO2R (cutoff 1.5 fold)