Molecule Information

General Information of the Molecule (ID: Mol00396)

Name	Glutamate--cysteine ligase regulatory subunit (GCLM) ,Homo sapiens
Synonyms	GCS light chain; Gamma-ECS regulatory subunit; Gamma-glutamylcysteine synthetase regulatory subunit; Glutamate--cysteine ligase modifier subunit; GLCLR Click to Show/Hide
Molecule Type	Protein
Gene Name	GCLM
Gene ID	2730
Location	chr1:93885199-93909456[-]
Sequence	MGTDSRAAKALLARARTLHLQTGNLLNWGRLRKKCPSTHSEELHDCIQKTLNEWSSQINP DLVREFPDVLECTVSHAVEKINPDEREEMKVSAKLFIVESNSSSSTRSAVDMACSVLGVA QLDSVIIASPPIEDGVNLSLEHLQPYWEELENLVQSKKIVAIGTSDLDKTQLEQLYQWAQ VKPNSNQVNLASCCVMPPDLTAFAKQFDIQLLTHNDPKELLSEASFQEALQESIPDIQAH EWVPLWLLRYSVIVKSRGIIKSKGYILQAKRRGS Click to Show/Hide
Uniprot ID	GSH0_HUMAN
Ensembl ID	ENSG00000023909
HGNC ID	HGNC:4312
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

1 drug(s) in total

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Cisplatin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Ovarian cancer				[1]
Resistant Disease	Ovarian cancer [ICD-11: 2C73.0]			Disease Info
Resistant Drug	Cisplatin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	A2780-DR cells	Ovary	Homo sapiens (Human)	CVCL_EG64
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Clonogenic assay
Mechanism Description	The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer.Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19-knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

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Ovarian cancer [ICD-11: 2C73]

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Differential expression of molecule in resistant diseases
The Studied Tissue	Ovary
The Specified Disease	Ovarian cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.55E-01; Fold-change: 6.08E-01; Z-score: 4.83E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue	p-value: 1.10E-01; Fold-change: -9.79E-01; Z-score: -7.26E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients Molecule expression in the diseased tissue of patients Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances		Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section Download Molecule expression data of patients in the disease section of the tissue Download Molecule expression data in the tissue of healthy individual

Tissue-specific Molecule Abundances in Healthy Individuals

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Download the Tissue-Specific Variation(s) Profile

References

Ref 1	The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer. Sci Rep. 2016 May 19;6:26093. doi: 10.1038/srep26093.