Glutaredoxin-related protein 5, mitochondrial (GLRX5)
The protein contains 157 amino acids for an estimated molecular weight of 16628 Da.
Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer (PubMed:20364084, PubMed:23615440). Receives 2Fe/2S clusters from scaffold protein ISCU and mediates their transfer to apoproteins, to the 4Fe/FS cluster biosynthesis machinery, or export from mitochondrion (PubMed:20364084, PubMed:23615440, PubMed:24334290). Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1 (PubMed:20364084). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| 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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| Variant | Description |
|---|---|
| SIDBA3 | |
| dbSNP:rs11628901 | |
| SIDBA3 |
Biological Process
Cell redox homeostasis
Hemopoiesis
Iron-sulfur cluster assembly
Protein lipoylation
Protein maturation by [2Fe-2S] cluster transfer
Protein maturation by [4Fe-4S] cluster transfer
Small molecule metabolic process
[2Fe-2S] cluster assembly
Cellular Component
Dendrite
Mitochondrial matrix
Mitochondrion
Neuronal cell body
Nucleus
Obsolete cell
The reference OMIM entry for this protein is 609588
Glutaredoxin 5; glrx5
Grx5
C14orf87
Pro1238
Flb4739
CLONING
Strausberg et al. (2002) identified the human GLRX5 gene as C14ORF87. Wingert et al. (2005) determined that the human GLRX5 gene encodes a 157-amino acid protein that is highly conserved among zebrafish, mouse, and human.GENE FUNCTION
Wingert et al. (2005) found high expression of Grx5 in developing blood and in liver and heart of zebrafish. In mice, Grx5 expression at embryonic day 7.5 (E7.5) was ubiquitous, but preferential expression in yolk sac blood islands was evident by E8.5. There was progressive downregulation of Grx5 in maturing primitive red cells between E10.5 and E12.5 and high expression in fetal liver at E12.5.MAPPING
Wingert et al. (2005) mapped the GLRX5 gene to human 14q32 using homology of synteny between human and zebrafish.MOLECULAR GENETICS
In a southern Italian man with autosomal recessive pyridoxine-refractory sideroblastic anemia (205950), Camaschella et al. (2007) identified a homozygous mutation in the GLRX5 gene (609588.0001).ANIMAL MODEL
Wingert et al. (2005) showed that the hypochromic anemia in 'shiraz' (sir) zebrafish mutants is caused by deficiency of grx5, a gene required in yeast for Fe/S cluster assembly. Wingert et al. (2005) found that grx5 is expressed in erythroid cells of zebrafish and mice. Zebrafish grx5 rescued the assembly of delta-grx5 yeast Fe/S, showing that the biochemical function of grx5 is evolutionarily conserved. In contrast to yeast, vertebrates use iron regulatory protein-1 (IRP1; 100880) to sense intracellular iron and regulate mRNA stability or the translation of iron metabolism genes. Wingert et al. (2005) found that loss of Fe/S cluster assembly in sir animals activated IRP1 and blocked heme biosynthesis catalyzed by aminolevulinate synthase-2 (ALAS2; 301300). Overexpression of ALAS2 RNA without the 5-prime iron response element that binds IRP1 rescued sir embryos, whereas overexpression of ALAS2, including the iron response element, did not. Further, antisense knockdown of IRP1 restored sir embryo hemoglobin synthesis. Wingert et al. (2005) concluded that their findings uncover a connection between heme biosynthesis and Fe/S clusters, indicating that hemoglobin production in the differentiating red cell is regulated through Fe/S cluster assembly. ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 609588 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).