Gamma-glutamylcyclotransferase (GGCT)
The protein contains 188 amino acids for an estimated molecular weight of 21008 Da.
Catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides and may play a significant role in glutathione homeostasis. Induces release of cytochrome c from mitochondria with resultant induction of apoptosis. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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The reference OMIM entry for this protein is 137170
Gamma-glutamyl cyclotransferase; ggct
Glutamylcyclotransferase, gamma; gctg
Chromosome 7 open reading frame 24; c7orf24
Cytochrome c-releasing factor, 21-kd; crf21
DESCRIPTION
GGCT (EC 2.3.2.4) catalyzes the formation of 5-oxoproline (pyroglutamic acid) from gamma-glutamyl dipeptides and may play a significant role in glutathione homeostasis (Oakley et al., 2008).CLONING
By mass spectrometric analysis of peptides obtained from an apoptosis-inducing protein, followed by database analysis and RT-PCR of total RNA from a human leukemia cell line, Masuda et al. (2006) cloned GGCT, which they called CRF21. SDS-PAGE detected purified CRF21 at an apparent molecular mass of 21 kD. Using tryptic peptides obtained from GGCT partially purified from expired human red blood cells for database analysis, Oakley et al. (2008) obtained a full-length GGCT cDNA. The deduced 188-amino acid protein has a calculated molecular mass of 21 kD. EST database analysis revealed moderate GGCT expression in a wide range of human tissues, with highest levels in bladder and salivary gland. Database analysis identified GGCT orthologs in a range of species from C. elegans to mammals, but not in plants.GENE FUNCTION
Geranylgeraniol (GGO) induces apoptosis in human tumor cell lines through a mitochondria-dependent pathway that includes cytochrome c release. Masuda et al. (2006) found that GGO was unable to induce cytochrome c release from isolated human mitochondria directly, and they identified CRF21 as a cytosolic cytochrome c-releasing factor involved in GGO-induced apoptosis. Overexpression of CRF21 in HeLa cells induced cytochrome c release and apoptosis. Masuda et al. (2006) noted that GGO-induced apoptosis was inhibited by a dominant-negative mutation of JNK (MAPK8; 601158) that impeded JNK signaling, suggesting involvement of JNK and CRF21 in GGO-induced apoptosis. Oakley et al. (2008) confirmed that recombinant human GGCT used gamma-glutamyl-L-alanine as its substrate. The enzymatic kinetics were similar to those of GGCT purified from human erythrocytes.BIOCHEMICAL FEATURES
- Crystal Structure Oakley et al. (2008) determined the crystal structure of recombinant human GGCT to 2.4-angstrom resolution. GGCT adopted a mixed alpha/beta topology with 6 beta stands, 5 alpha helices, and 4 short 3(10) helices, and it assumed a unique structural fold that the authors termed a GGCT fold. GGCT formed dimers, and each monomer featured an invagination that Oakley et al. (2008) proposed was the active site. The site was lined with hydrophilic and amphipathic residues, including a conserved glu98 that appeared to function as a general acid/base in the reaction. Mutation of glu98 to ala or gln did not alter the structural fold, but it completely inactivated the enzyme. Mutation analysis showed that gly23 and tyr105 also contributed to substrate binding interactions.GENE STRUCTURE
Oakley et al. (2008) determined that the GGCT gene contains 5 exons and spans 8 kb.MAPPING
Bissbort et al. (1984) assigned the GGCT gene to chromosome 7pter-p14 by somatic cell hybrid studies. By genomic sequence analysis, Oakley et al. (2008) mapped the GGCT gene to chromosome 7p15-p14. They identified putative GGCT pseudogenes on chromosomes 5 and 20. Oakley et al. (2008) noted that the mouse Ggct gene maps to a region of chromosome 6 that shares homology of synteny with human chromosome 7p15-p14. ... More on the omim web site
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 137170 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed