GLRX5
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGLRX5, C14orf87, FLB4739, GRX5, PR01238, PRO1238, PRSA, SIDBA3, SPAHGC, glutaredoxin 5
External IDsOMIM: 609588 MGI: 1920296 HomoloGene: 31984 GeneCards: GLRX5
Orthologs
SpeciesHumanMouse
Entrez

51218

73046

Ensembl

ENSG00000182512

ENSMUSG00000021102

UniProt

Q86SX6

Q80Y14

RefSeq (mRNA)

NM_016417

NM_028419

RefSeq (protein)

NP_057501

NP_082695

Location (UCSC)Chr 14: 95.53 – 95.54 MbChr 12: 105 – 105.01 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Glutaredoxin 5, also known as GLRX5, is a protein which in humans is encoded by the GLRX5 gene located on chromosome 14.[5] 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.[6]

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.[7] Crystal structure of the GLRX5 protein reveals that the protein likely exists as a tetramer with two Fe-S clusters buried in the interior.[8]

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,[9] 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.[10]

Clinical significance

Mutations in the GLRX5 gene have been associated with sideroblastic anemia,[11] variant glycine encephalopathy (also known as non-ketotic hyperglycinemia, NKH).[12] as well as pyridoxine-refractory, autosomal recessive anemia (PRARSA).[10] Cells with mutations in GLRX5 activity show deficiency in Fe-S cluster synthesis, which is likely causative of the observed symptoms.[7]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000182512 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021102 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Wingert RA, Galloway JL, Barut B, Foott H, Fraenkel P, Axe JL, Weber GJ, Dooley K, Davidson AJ, Schmid B, Schmidt B, Paw BH, Shaw GC, Kingsley P, Palis J, Schubert H, Chen O, Kaplan J, Zon LI (Aug 2005). "Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis". Nature. 436 (7053): 1035–39. Bibcode:2005Natur.436.1035W. doi:10.1038/nature03887. PMID 16110529. S2CID 4333813.
  6. ↑ "GLRX5 glutaredoxin 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-26.
  7. 1 2 Ye H, Jeong SY, Ghosh MC, Kovtunovych G, Silvestri L, Ortillo D, Uchida N, Tisdale J, Camaschella C, Rouault TA (2010). "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. doi:10.1172/JCI40372. PMC 2860907. PMID 20364084.
  8. ↑ Johansson C, Roos AK, Montano SJ, Sengupta R, Filippakopoulos P, Guo K, von Delft F, Holmgren A, Oppermann U, Kavanagh KL (2011). "The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity". Biochem. J. 433 (2): 303–11. doi:10.1042/BJ20101286. hdl:10616/41576. PMID 21029046.
  9. ↑ Wingert RA, Galloway JL, Barut B, Foott H, Fraenkel P, Axe JL, Weber GJ, Dooley K, Davidson AJ, Schmid B, Schmidt B, Paw BH, Shaw GC, Kingsley P, Palis J, Schubert H, Chen O, Kaplan J, Zon LI (2005). "Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis". Nature. 436 (7053): 1035–39. Bibcode:2005Natur.436.1035W. doi:10.1038/nature03887. PMID 16110529. S2CID 4333813.
  10. 1 2 Camaschella 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. PMID 17485548.
  11. ↑ 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. PMID 18637800.
  12. ↑ Baker PR, Friederich MW, Swanson MA, Shaikh T, Bhattacharya K, Scharer GH, Aicher J, Creadon-Swindell G, Geiger E, MacLean KN, Lee WT, Deshpande C, Freckmann ML, Shih LY, Wasserstein M, Rasmussen MB, Lund AM, Procopis P, Cameron JM, Robinson BH, Brown GK, Brown RM, Compton AG, Dieckmann CL, Collard R, Coughlin CR, Spector E, Wempe MF, Van Hove JL (Feb 2014). "Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5". Brain. 137 (Pt 2): 366–79. doi:10.1093/brain/awt328. PMC 3914472. PMID 24334290.

Further reading

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