GSS glutathione synthetase [Homo sapiens] - Gene

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Summary

Official Symbol: GSSprovided by HGNC
Official Full Name: glutathione synthetaseprovided by HGNC
Primary source: HGNC:4624
See related: Ensembl:ENSG00000100983; HPRD:03000; MIM:601002; Vega:OTTHUMG00000032315
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: GSHS; MGC14098
Summary: Glutathione is important for a variety of biological functions, including protection of cells from oxidative damage by free radicals, detoxification of xenobiotics, and membrane transport. The protein encoded by this gene functions as a homodimer to catalyze the second step of glutathione biosynthesis, which is the ATP-dependent conversion of gamma-L-glutamyl-L-cysteine to glutathione. Defects in this gene are a cause of glutathione synthetase deficiency. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 20q11.2

Sequence :: Chromosome: 20; NC_000020.10 (33516236..33543601, complement)

See GSS in Epigenomics, MapViewer

Chromosome 20 - NC_000020.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

The findings indicate that Asp458 is essential for hGS catalysis and that it impacts the allostery of hGS.
Title: Aspartate 458 of human glutathione synthetase is important for cooperativity and active site structure.
These results imply that residues V44 and V45 are integral to the stability of human glutathione synthetase.
Title: Valine 44 and valine 45 of human glutathione synthetase are key for subunit stability and negative cooperativity.
SNPs not associted with schizophrenia in Japanese individuals
Title: No association between glutathione-synthesis-related genes and Japanese schizophrenia.
We have shown that susceptibility to health effects of air pollution on lung function growth is associated with genetic variation in the GSS gene
Title: Genetic variation in the glutathione synthesis pathway, air pollution, and children's lung function growth.
Single-nucleotide polymorphism in glutathione synthetase is associated with small-cell lung cancer.
Title: Genetic variation in glutathione metabolism and DNA repair genes predicts survival of small-cell lung cancer patients.
This research indicates that Gly369 and Gly370 have essential roles in hGS, while Gly371 has a lesser involvement.
Title: The role of the glycine triad in human glutathione synthetase.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
the cause of cellular ATP depletion in nephrotic cystinosis may be the futile cycle, formed between two ATP-dependant gamma-glutamyl cycle enzymes, gamma-glutamyl cysteine synthetase and 5-oxoprolinase
Title: A futile cycle, formed between two ATP-dependant gamma-glutamyl cycle enzymes, gamma-glutamyl cysteine synthetase and 5-oxoprolinase: the cause of cellular ATP depletion in nephrotic cystinosis?
A novel alternative splicing variant (ASV) of the GSS gene was identified in 10 human normal tissues and five human cancer cell lines.
Title: Alternative RNA splicing in expression of the glutathione synthetase gene in human cells.
Severe glutathione synthetase deficiency is associated with progressive retinal dystrophy of the rod-cone type, affecting the central retina with advanced macular edema in adulthood.
Title: Rod-cone dystrophy with maculopathy in genetic glutathione synthetase deficiency: a morphologic and electrophysiologic study.

Submit: New GeneRIF Correction See all (16)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Glutathione synthetase deficiency

MIM: 266130

Hemolytic anemia due to glutathione synthetase deficiency

MIM: 231900

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat causes a greater than 50% decrease in intracellular reduced glutathione (GSH), leading to the extracellular appearance of acidic FGF-1, an effect that is partially mediated through modulation of GSH biosynthetic enzymes	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
P48637	P48637	GSS	HPRD	PubMed
P48637	O43708	GSTZ1	HPRD	PubMed
BioGRID:109192	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
glutathione binding	IDA Inferred from Direct Assay more info	PubMed
glutathione synthase activity	TAS Traceable Author Statement more info
glycine binding	IEA Inferred from Electronic Annotation more info
ligase activity	IEA Inferred from Electronic Annotation more info
magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
aging	IEA Inferred from Electronic Annotation more info
cellular amino acid metabolic process	TAS Traceable Author Statement more info	PubMed
glutathione biosynthetic process	TAS Traceable Author Statement more info
nervous system development	TAS Traceable Author Statement more info	PubMed
response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
response to cadmium ion	IEA Inferred from Electronic Annotation more info
response to nutrient levels	IEA Inferred from Electronic Annotation more info
response to oxidative stress	TAS Traceable Author Statement more info	PubMed
response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
xenobiotic metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info
soluble fraction	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: glutathione synthetase

Names: glutathione synthetase; GSH-S; GSH synthetase; glutathione synthase

NP_000169.1

EC 6.3.2.3

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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

NG_008848.1 RefSeqGene

Range

5001..32366

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000178.2 → NP_000169.1 glutathione synthetase

Status: REVIEWED

Source sequence(s)

BC007927

Consensus CDS

CCDS13245.1

UniProtKB/Swiss-Prot

P48637

Related

ENSP00000216951, OTTHUMP00000030711, ENST00000216951, OTTHUMT00000078821

Conserved Domains (1) summary

cd00228
Location:6 – 474
Blast Score: 1781

eu-GS; Eukaryotic Glutathione Synthetase (eu-GS); catalyses the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. Belongs to the ATP-grasp superfamily.

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000020.10 Reference GRCh37.p5 Primary Assembly

Range

33516236..33543601, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000152.1 Alternate HuRef

Range

30294556..30321979, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF485789.1	AAL91591.1
genomic	AL133324.13	CAB93423.1
genomic	CH471077.2	EAW76239.1
		EAW76240.1
		EAW76241.1
genomic	DQ074975.1	AAY57328.1
mRNA	AB459500.1	BAG75452.1
mRNA	AK293144.1	BAH11461.1
mRNA	AK298292.1	BAH12750.1
mRNA	AK311421.1	None
mRNA	AK311567.1	None
mRNA	AK312492.1	BAG35394.1
mRNA	BC007927.1	AAH07927.1
mRNA	U34683.1	AAB62390.1
other-genetic	DQ893238.2	ABM84164.1
other-genetic	DQ896568.2	ABM87567.1