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]
↑ 6.06.1Camaschella C, Campanella A, De Falco L, Boschetto L, Merlini R, Silvestri L, Levi S, Iolascon A (2007). "The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload". Blood. 110 (4): 1353–8. doi:10.1182/blood-2007-02-072520. PMID17485548.
↑Camaschella C (Oct 2008). "Recent advances in the understanding of inherited sideroblastic anaemia". British Journal of Haematology. 143 (1): 27–38. doi:10.1111/j.1365-2141.2008.07290.x. PMID18637800.
Davis DA, Newcomb FM, Starke DW, Ott DE, Mieyal JJ, Yarchoan R (Oct 1997). "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. doi:10.1074/jbc.272.41.25935. PMID9325327.
Camaschella C, Campanella A, De Falco L, Boschetto L, Merlini R, Silvestri L, Levi S, Iolascon A (Aug 2007). "The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload". Blood. 110 (4): 1353–8. doi:10.1182/blood-2007-02-072520. PMID17485548.
