Glutamate--cysteine ligase regulatory subunit (GCLM)

The protein contains 274 amino acids for an estimated molecular weight of 30727 Da.

 

No function (updated: Feb. 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 80

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VariantDescription
dbSNP:rs17880087

The reference OMIM entry for this protein is 601176

Glutamate-cysteine ligase, modifier subunit; gclm
Glutamate-cysteine ligase, regulatory; glclr
Gamma-glutamylcysteine synthetase, regulatory subunit

DESCRIPTION

Gamma-glutamylcysteine synthetase, also known as glutamate-cysteine ligase (EC 6.3.2.2), is the first rate-limiting enzyme in glutathione biosynthesis.

CLONING

Human liver gamma-glutamylcysteine synthetase consists of 2 subunits: a heavy catalytic subunit (GCLC; 606857) and a light regulatory subunit. Gipp et al. (1995) reported the cloning of a full-length cDNA for the light subunit. The cDNA encodes a 274-amino acid protein of approximately 30.7 kD that is 96% identical to the previously cloned rat sequence (Huang et al., 1993). Northern blot analysis detected 1.4- and 4.1-kb transcripts in several tissue types. The smaller transcript was detected in the colon, whereas both forms were found in skeletal muscle.

GENE STRUCTURE

Rozet et al. (1998) determined that the GLCLR gene encompasses 22 kb and contains 7 exons.

MAPPING

By fluorescence in situ hybridization (FISH), Tsuchiya et al. (1995) mapped the human GLCLR gene to 1p22-p21 and the mouse gene to 3H1-3. By Southern blot analysis of DNA from a panel of somatic cell hybrids, Sierra-Rivera et al. (1996) assigned GLCLR to chromosome 1; sublocalization to 1p21 was achieved by FISH. Rozet et al. (1998) found an EST of GLCLR within a YAC contig encompassing the critically deleted region of human malignant mesothelioma, between loci D1S435 and D1S236. They refined the physical mapping of GLCLR to 1p22.1.

MOLECULAR GENETICS

Nakamura et al. (2002) reported an association between a polymorphism in the GCLM gene (601176.0001) and myocardial infarction (608446). Schizophrenia (181500) is a major and frequent chronic psychiatric disorder with a strong genetic component. Converging evidence points to the involvement of oxidative stress and N-methyl D-aspartate (NMDA) receptor (138249) hypofunction in the pathophysiology of the disease. As a main cellular nonprotein antioxidant and redox regulator, glutathione (GSH) plays a major role in protecting nervous tissue against reactive oxygen species and in modulating redox-sensitive sites, including NMDA receptors (NMDA-R). Tosic et al. (2006) noted that studies had found GSH levels to be decreased in patients' cerebrospinal fluid, in medial prefrontal cortex in vivo, and in striatum postmortem tissue. GSH-deficient models revealed morphologic, electrophysiologic, and behavioral anomalies similar to those observed in patients. Tosic et al. (2006) found an association between schizophrenia and the gene of the key GSH-synthesizing enzyme, GCLM. A functional role of the GCLM gene variance in schizophrenia was supported by its low expression in patients' fibroblasts and by the decreased stimulation of the enzyme activity when challenged by an oxidative stress. The findings were considered consistent with the concept that an abnormal GSH metabolism is a factor for schizophrenia. One of the case-control studies was conducted in Switzerland and the other in Denmark. Two particular combinations of variation at 3 SNPs related to the GCLM gene, TT/GG/TC and CC/GG/TT, had odds ratios of 4.89 and 4.17, respectively. Tosic et al. (2006) observed that the GCLM gene is localized on 1p21, a region shown by previous linkage studies to be one of the several critical for schizophrenia (Pulver et al., 2000, Arinami et al., 2005). ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601176 was added.