MSRA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMSRA, PMSR, methionine sulfoxide reductase A
External IDsOMIM: 601250 MGI: 106916 HomoloGene: 5812 GeneCards: MSRA
Orthologs
SpeciesHumanMouse
Entrez

4482

110265

Ensembl

ENSG00000175806
ENSG00000285250

ENSMUSG00000054733

UniProt

Q9UJ68

Q9D6Y7

RefSeq (mRNA)

NM_001135670
NM_001135671
NM_001199729
NM_012331

RefSeq (protein)

NP_001129142
NP_001129143
NP_001186658
NP_036463

Location (UCSC)Chr 8: 10.05 – 10.43 MbChr 14: 64.36 – 64.69 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Peptide methionine sulfoxide reductase (Msr) is a family of enzymes that in humans is encoded by the MSRA gene.[5][6]

Function

Msr is ubiquitous and highly conserved. Human and animal studies have shown the highest levels of expression in kidney and liver. It carries out the enzymatic reduction of methionine sulfoxide (MetO), the oxidized form of the amino acid methionine (Met), back to methionine, using thioredoxin to catalyze the enzymatic reduction and repair of oxidized methionine residues.[7] Its proposed function is thus the repair of oxidative damage to proteins to restore biological activity.[6] Oxidation of methionine residues in tissue proteins can cause them to misfold or otherwise render them dysfunctional.[7]

Clinical significance

MetO increases with age in body tissues, which is believed by some to contribute to biological ageing.[7][8] Moreover, levels of methionine sulfoxide reductase A (MsrA) decline in aging tissues in mice and in association with age-related disease in humans.[7] There is thus a rationale for thinking that by maintaining the structureincreased levels or activity of MsrA might retard the rate of aging.

Indeed, transgenic Drosophila (fruit flies) that overexpress methionine sulfoxide reductase show extended lifespan.[9] However, the effects of MsrA overexpression in mice were ambiguous.[10] MsrA is found in both the cytosol and the energy-producing mitochondria, where most of the body's endogenous free radicals are produced. Transgenically increasing the levels of MsrA in either the cytosol or the mitochondria had no significant effect on lifespan assessed by most standard statistical tests, and may possibly have led to early deaths in the cytosol-specific mice, although the survival curves appeared to suggest a slight increase in maximum (90%) survivorship, as did analysis using Boschloo's test, a binomial test designed to test greater extreme variation.[10]

Deletion of this gene has been associated with insulin resistance in mice,[11] while overexpression reduces insulin resistance in old mice.[10]

See also

References

  1. 1 2 3 ENSG00000285250 GRCh38: Ensembl release 89: ENSG00000175806, ENSG00000285250 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000054733 - 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. ↑ Kuschel L, Hansel A, Schonherr R, Weissbach H, Brot N, Hoshi T, Heinemann SH (Sep 1999). "Molecular cloning and functional expression of a human peptide methionine sulfoxide reductase (hMsrA)". FEBS Lett. 456 (1): 17–21. doi:10.1016/S0014-5793(99)00917-5. PMID 10452521. S2CID 19104671.
  6. 1 2 "Entrez Gene: MSRA methionine sulfoxide reductase A".
  7. 1 2 3 4 Stadtman ER, Van Remmen H, Richardson A, Wehr NB, Levine RL (2005). "Methionine oxidation and aging". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1703 (2): 135–140. doi:10.1016/j.bbapap.2004.08.010. PMID 15680221.
  8. ↑ Shringarpure R, Davies KJ (2002). "Protein turnover by the proteasome in aging and disease". Free Radical Biology & Medicine. 32 (11): 1084–1089. doi:10.1016/S0891-5849(02)00824-9. PMID 12031893.
  9. ↑ Ruan H, Tang XD, Chen ML, Joiner ML, Sun G, Brot N, Weissbach H, Heinemann SH, Iverson L, Wu CF, Hoshi T (2002). "High-quality life extension by the enzyme peptide methionine sulfoxide reductase". Proceedings of the National Academy of Sciences of the United States of America. 99 (5): 2748–2753. Bibcode:2002PNAS...99.2748R. doi:10.1073/pnas.032671199. PMC 122419. PMID 11867705.
  10. 1 2 3 Salmon AB, Kim G, Liu C, Wren JD, Georgescu C, Richardson A, Levine RL (December 2016). "Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice". Redox Biol. 10: 251–256. doi:10.1016/j.redox.2016.10.012. PMC 5099276. PMID 27821326.
  11. ↑ Styskal JL, Nwagwu FA, Watkins YN, Liang H, Richardson A, Musi N, Salmon AB (October 2012). "Methionine sulfoxide reductase a affects insulin resistance by protecting insulin receptor function". Free Radic. Biol. Med. 56: 123–32. doi:10.1016/j.freeradbiomed.2012.10.544. PMC 3578155. PMID 23089224.

Further reading


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