Glutaredoxin 5, also known as GLRX5, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

which in humans is encoded by the ''GLRX5''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

located on

chromosome 14 Chromosome 14 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 14 spans about 107 million base pairs (the building material of DNA) and represents between 3 and 3.5% of the total DNA ...

. This gene encodes a

mitochondrial A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...

protein, which is evolutionarily conserved. It is involved in the biogenesis of iron- sulfur clusters, which are required for normal

iron homeostasis Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically imp ...

. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory

sideroblastic anemia Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). In sideroblastic anemia, the body has iron available but cannot incorpora ...

Structure

The GLRX5 gene contains 2

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

and encodes for a protein that is 13 kDa in size. The protein is highly expressed in erythroid cells.

Crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystal, crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric pat ...

of the GLRX5 protein reveals that the protein likely exists as a tetramer with two Fe-S clusters buried in the interior.

Function

GLRX5 is a

protein is conserved evolutionarily and plays a role in the formation of

iron-sulfur clusters Iron–sulfur proteins (or iron–sulphur proteins in British spelling) are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur cl ...

, which function to maintain

within the mitochondria and in the cell. GLRX5 is required for the steps in haem synthesis that involves mitochondrial enzymes, and is therefore involved in

hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

. GLRX5 activity is required for normal regulation of hemoglobin synthesis by the iron-sulfur protein

ACO1 Aconitase 1, soluble is a protein that in humans is encoded by the ACO1 gene. Function The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to cont ...

. The function of GLRX5 is highly conserved evolutionarily.

Clinical significance

Mutations in the GLRX5 gene have been associated with

, variant

glycine encephalopathy Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine cleava ...

(also known as non-ketotic hyperglycinemia,

NKH Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine clea ...

). as well as pyridoxine-refractory, autosomal recessive anemia (PRARSA). Cells with mutations in GLRX5 activity show deficiency in Fe-S cluster synthesis, which is likely causative of the observed symptoms.

Structure

Function

Clinical significance

See also

References

Further reading