Biology:GLRX5
 Generic protein structure example |
Glutaredoxin 5, also known as GLRX5, is a protein which in humans is encoded by the GLRX5 gene located on chromosome 14.[1] This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron- sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia.[2]
Structure
The GLRX5 gene contains 2 exons and encodes for a protein that is 13 kDa in size. The protein is highly expressed in erythroid cells.[3] Crystal structure of the GLRX5 protein reveals that the protein likely exists as a tetramer with two Fe-S clusters buried in the interior.[4]
Function
GLRX5 is a mitochondrial protein is conserved evolutionarily and plays a role in the formation of iron-sulfur clusters, which function to maintain iron homeostasis within the mitochondria and in the cell. GLRX5 is required for the steps in haem synthesis that involves mitochondrial enzymes,[5] and is therefore involved in hematopoiesis. GLRX5 activity is required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1. The function of GLRX5 is highly conserved evolutionarily.[6]
Clinical significance
Mutations in the GLRX5 gene have been associated with sideroblastic anemia,[7] variant glycine encephalopathy (also known as non-ketotic hyperglycinemia, NKH).[8] as well as pyridoxine-refractory, autosomal recessive anemia (PRARSA).[6] Cells with mutations in GLRX5 activity show deficiency in Fe-S cluster synthesis, which is likely causative of the observed symptoms.[3]
See also
References
- ↑ "Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis". Nature 436 (7053): 1035–39. Aug 2005. doi:10.1038/nature03887. PMID 16110529. Bibcode: 2005Natur.436.1035W.
- ↑ "GLRX5 glutaredoxin 5 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/51218.
- ↑ 3.0 3.1 "Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts". J. Clin. Invest. 120 (5): 1749–61. 2010. doi:10.1172/JCI40372. PMID 20364084.
- ↑ "The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity". Biochem. J. 433 (2): 303–11. 2011. doi:10.1042/BJ20101286. PMID 21029046.
- ↑ "Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis". Nature 436 (7053): 1035–39. 2005. doi:10.1038/nature03887. PMID 16110529. Bibcode: 2005Natur.436.1035W.
- ↑ 6.0 6.1 "The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload". Blood 110 (4): 1353–8. 2007. doi:10.1182/blood-2007-02-072520. PMID 17485548.
- ↑ "Recent advances in the understanding of inherited sideroblastic anaemia". British Journal of Haematology 143 (1): 27–38. Oct 2008. doi:10.1111/j.1365-2141.2008.07290.x. PMID 18637800.
- ↑ "Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5". Brain 137 (Pt 2): 366–79. Feb 2014. doi:10.1093/brain/awt328. PMID 24334290.
Further reading
- "Thioltransferase (glutaredoxin) is detected within HIV-1 and can regulate the activity of glutathionylated HIV-1 protease in vitro". The Journal of Biological Chemistry 272 (41): 25935–40. Oct 1997. doi:10.1074/jbc.272.41.25935. PMID 9325327.
- "The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload". Blood 110 (4): 1353–8. Aug 2007. doi:10.1182/blood-2007-02-072520. PMID 17485548.
- "Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations". Pediatric Blood & Cancer 54 (2): 273–8. Feb 2010. doi:10.1002/pbc.22244. PMID 19731322.
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