Affinage

MSRA

Mitochondrial peptide methionine sulfoxide reductase · UniProt Q9UJ68

Length
235 aa
Mass
26.1 kDa
Annotated
2026-06-10
95 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MSRA is a stereospecific methionine sulfoxide reductase that constitutes a core antioxidant defense system by catalytically repairing oxidized proteins and restoring their function (PMID:11606777, PMID:19461988). Catalysis depends on a conserved active-site cysteine within the GCFWG motif, which forms a sulfenic acid intermediate during reduction; invariant Glu, Tyr, and a second Tyr stabilize the sulfurane transition state and lower the catalytic cysteine pKa, and the enzyme is strictly stereoselective for the S-epimer of methionine sulfoxide (PMID:10799493, PMID:17062561, PMID:18697736). A single gene generates multiple isoforms from two promoters: an upstream promoter drives a mitochondrial-matrix isoform via a cleavable N-terminal 23-residue targeting sequence, while a downstream promoter drives cytosolic and nuclear isoforms, and this compartmentalization dictates distinct physiological consequences (PMID:12039877, PMID:12693988, PMID:16364291, PMID:18845237). Through methionine repair MSRA restores activity to oxidatively damaged substrates including cytochrome c (recovering electron-transport-chain function) and alpha-crystallin (recovering chaperone activity) (PMID:19461988, PMID:19733220), and its loss in knockout mice causes accumulation of oxidized proteins, heightened oxidative-stress sensitivity, and shortened lifespan (PMID:11606777). Compartment-specific transgenic studies show mitochondrial MSRA preserves insulin sensitivity via AMPK signaling whereas cytosolic MSRA modulates age-related mortality, establishing localization-dependent roles in metabolism and aging (PMID:26448611, PMID:27821326). Beyond canonical reductase chemistry, MSRA participates in protein modification and signaling: it engages a ubiquitin-like conjugation activity through its active site, mediates ubiquitination of 14-3-3 and alpha-synuclein, enhances Jab1/CSN5 deneddylase activity to drive p27 degradation, and acts upstream of the p38 MAPK pathway by reducing oxidized CaMKII (PMID:28874471, PMID:30096435, PMID:32456285, PMID:39157962).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2000 High

    Establishing the catalytic basis and substrate selectivity of MsrA was needed to define it as a true methionine sulfoxide reductase rather than a generic redox protein.

    Evidence Site-directed mutagenesis of the GCFWG cysteine, iodoacetamide inactivation, and stereospecificity assays with S/R methionine sulfoxide in yeast MsrA

    PMID:10799493

    Open questions at the time
    • Catalytic mechanism of intermediate resolution not yet defined
    • Did not address subcellular localization or substrates in vivo
  2. 2001 High

    Genetic loss-of-function tested whether MsrA matters at the organismal level, defining it as an antioxidant defense and lifespan regulator.

    Evidence MsrA knockout mouse exposed to hyperoxia, with protein carbonyl, lifespan, and thioredoxin reductase measurements

    PMID:11606777

    Open questions at the time
    • Specific oxidized protein substrates driving phenotype not identified
    • Mechanistic link between methionine repair and lifespan unresolved
  3. 2002 High

    Defining the mitochondrial targeting sequence answered where MSRA acts and separated localization from catalysis.

    Evidence EGFP-fusion imaging, deletion constructs, immuno-EM in liver, and in vitro activity assays

    PMID:12039877

    Open questions at the time
    • Did not resolve how non-mitochondrial isoforms are generated
    • Regulation of targeting not addressed
  4. 2003 High

    Showing a single gene yields both mitochondrial and cytosolic isoforms clarified the structural basis for compartmental distribution.

    Evidence Subcellular fractionation, immuno-EM, mass spectrometry, and 2D gels of rat liver MsrA

    PMID:12693988

    Open questions at the time
    • Promoter/transcript origin of isoforms not yet mapped
    • Functional difference between isoforms untested
  5. 2005 High

    Mapping two promoters generating three isoforms with distinct localizations explained how subcellular distribution is encoded, and knockdown confirmed a protective role.

    Evidence 5'RACE, promoter analysis, isoform-GFP localization, and siRNA knockdown with oxidative-stress viability in RPE cells

    PMID:16364291

    Open questions at the time
    • Distinct functional consequences of each isoform not dissected
    • Transcriptional control of promoters not addressed
  6. 2006 High

    Dissecting active-site residues defined the catalytic chemistry of the reductase step at residue resolution.

    Evidence Site-directed mutagenesis and kinetic analysis of Glu/Tyr/Tyr and catalytic Cys in Neisseria MsrA

    PMID:17062561

    Open questions at the time
    • Generality to mammalian enzyme inferred from bacterial ortholog
    • Regeneration step of active site not characterized here
  7. 2008 High

    Distinguishing free amino-acid substrate specificity in vivo confirmed MsrA reduces only the S-epimer of free methionine sulfoxide.

    Evidence MsrA knockout mouse plasma sulfoxide measurement, cell culture, and yeast complementation

    PMID:18697736

    Open questions at the time
    • R-epimer reduction pathway handled by separate enzymes, not addressed
    • Protein-bound versus free substrate preference not compared
  8. 2008 Medium

    Connecting MsrA loss to dopamine dysregulation extended its role into neurological homeostasis.

    Evidence MsrA knockout mouse dopamine and locomotor measurements with tyrosine hydroxylase analysis

    PMID:18466776

    Open questions at the time
    • Direct molecular target in dopamine pathway not identified
    • Correlation between dopamine levels and MsrA status does not establish causal mechanism
  9. 2008 Medium

    Hormonal induction of MsrA by ecdysone linked oxidative-stress resistance to developmental signaling in Drosophila.

    Evidence Ecdysone treatment of Kc cells, RT-PCR, H2O2 viability, and EcR-knockout comparison

    PMID:17239346

    Open questions at the time
    • Mammalian relevance of ecdysone regulation not applicable
    • Direct EcR-USP binding to MsrA promoter not shown
  10. 2008 Medium

    Characterizing dual-promoter retinoic-acid regulation revealed how isoform expression is transcriptionally tuned.

    Evidence Promoter-reporter assays, deletion analysis, retinoic acid treatment, and RAR siRNA knockdown

    PMID:18845237

    Open questions at the time
    • Endogenous retinoid control in vivo not confirmed
    • Other transcription factors at the two promoters not mapped
  11. 2009 High

    Identifying specific protein substrates and repair outcomes showed how MSRA restores function to oxidatively damaged proteins.

    Evidence Co-IP, CNBr cleavage with mass spectrometry of oxidized methionines, in vitro repair with activity assays, and KO lens analysis for cytochrome c and alpha-crystallin

    PMID:19461988 PMID:19733220

    Open questions at the time
    • Full substrate repertoire beyond cytochrome c and crystallin not defined
    • In vivo flux of repair versus protein turnover not quantified
  12. 2015 Medium

    Compartment-specific overexpression demonstrated that mitochondrial MSRA controls metabolic homeostasis through AMPK signaling.

    Evidence TgMito versus TgCyto transgenic mice on high-fat diet with glucose/insulin tests and AMPK measurements

    PMID:26448611

    Open questions at the time
    • Mitochondrial substrate transmitting the AMPK signal not identified
    • Single-lab transgenic models
  13. 2016 Medium

    Compartment-specific transgenics linked cytosolic MSRA to age-related mortality independent of lifespan extension, establishing localization-dependent aging effects.

    Evidence Cytosol- and mitochondria-targeted transgenic mice with Gompertz/log-rank lifespan and insulin sensitivity analyses

    PMID:27821326

    Open questions at the time
    • Sex-specific effects not mechanistically explained
    • Molecular targets distinguishing the two compartments not identified
  14. 2017 Medium

    Discovery of a ubiquitin-like conjugation activity using the same active site revealed a moonlighting function distinct from methionine repair.

    Evidence In vitro Ubl modification assay with UbaA E1 and DMSO, LC-MS/MS conjugate identification, and active-site mutant analysis in archaea

    PMID:28874471

    Open questions at the time
    • Archaeal system; mammalian relevance requires inference
    • In vivo conjugate function not established
  15. 2018 Medium

    Demonstrating MsrA-mediated ubiquitination of 14-3-3 and alpha-synuclein extended the non-canonical modification activity to a mammalian, neurologically relevant context.

    Evidence Co-IP, ubiquitination and phosphorylation assays in brain tissue, KO comparison, and active-site competition assays

    PMID:30096435

    Open questions at the time
    • Direct catalytic role versus scaffolding not fully separated
    • Physiological consequence for synucleinopathy not established
  16. 2018 High

    Showing Drosophila MsrA lacks the oxidase step refined the mechanistic understanding of the active-site sulfenic acid chemistry across orthologs.

    Evidence Recombinant Drosophila MSRA in vitro reductase and oxidase assays with stepwise mechanistic dissection

    PMID:30529269

    Open questions at the time
    • Structural basis for the missing disulfide-exchange step not resolved
    • Physiological role of the oxidase activity unclear
  17. 2020 Medium

    Linking MSRA to Jab1/CSN5 deneddylase activity connected it to cell-cycle control through p27 degradation.

    Evidence Co-IP, deneddylase activity assay, Cullin-1 neddylation analysis, and p27 levels in MsrA-knockout cells

    PMID:32456285

    Open questions at the time
    • Whether MSRA repairs an oxidized methionine on Jab1 not shown
    • Single-lab characterization
  18. 2024 Medium

    Placing MSRA upstream of p38 MAPK via ox-CaMKII reduction defined a signaling axis protective against cardiac remodeling.

    Evidence Ang II mouse model, MsrA siRNA knockdown in HL-1 cells, RNA-seq, ox-CaMKII/p38 Western blots, and p38-inhibitor rescue

    PMID:39157962

    Open questions at the time
    • Direct repair of CaMKII methionines not biochemically confirmed in this study
    • Single-lab pharmacological pathway dissection
  19. 2025 Medium

    Iron-dependent multimerization and activation of MSRA, coupled to PKA methionine maintenance, mechanistically tied the enzyme to adipose browning and cancer cachexia.

    Evidence Iron-binding mutagenesis, biophysical multimer characterization, PKA methionine oxidation analysis, and MsrA knockout PDA mouse browning/survival measurements (preprint)

    PMID:bio_10.1101_2025.07.16.664180

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Structural details of iron-coordinated multimer not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how MSRA's canonical reductase activity and its non-canonical ubiquitin-like/signaling activities are coordinated in vivo, and which compartment-specific substrates drive its distinct metabolic, aging, and neurological roles.
  • No unifying structural model reconciling reductase and Ubl activities in mammals
  • Comprehensive compartment-resolved substrate maps lacking
  • Causal substrate for AMPK/PKA/p38 signaling effects unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 5 GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
CAMK2CRYAACRYABCYCSJAB1/CSN5PRKACASNCAYWHAZ

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 The conserved GCFWG motif in MsrA is essential for catalytic activity; site-directed mutagenesis of the cysteine within this motif (or treatment with iodoacetamide) causes complete loss of enzyme activity. The yeast MsrA is stereoselective for L-methionine S-sulfoxide (S-epimer), establishing substrate stereospecificity. Site-directed mutagenesis of active-site residues; iodoacetamide inactivation; in vitro enzymatic activity assays; circular dichroism; stereospecificity assays with S- and R-methionine sulfoxide The Journal of biological chemistry High 10799493
2001 MsrA knockout mice exhibit enhanced sensitivity to oxidative stress, shorter lifespan, accumulation of oxidized proteins, and impaired upregulation of thioredoxin reductase under oxidative stress, establishing MsrA as a key antioxidant defense and lifespan regulator in mammals. MsrA knockout mouse model; exposure to 100% oxygen; protein carbonyl measurements; lifespan analysis; Western blotting for thioredoxin reductase Proceedings of the National Academy of Sciences of the United States of America High 11606777
2002 Human MSRA is targeted to the mitochondrial matrix via an N-terminal 23 amino acid mitochondrial targeting sequence. The N-terminal signal sequence is not required for catalytic enzyme activity. EGFP fusion protein imaging in mammalian cell lines; deletion constructs; immunohistochemistry of mouse and rat liver; pre-embedding immunostaining with electron microscopy; in vitro activity assays FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 12039877
2003 Rat liver MsrA exists as both mitochondrial matrix and cytosolic isoforms encoded by a single gene; the mitochondrial form contains a cleavable N-terminal signal sequence. Both isoforms carry oxidative modifications of cysteine residues in native tissue. Subcellular fractionation; enzymatic activity assays; Western blotting; immunoelectron microscopy; mass spectrometry identification; 2D gel electrophoresis The Biochemical journal High 12693988
2005 The human MSRA gene produces three isoforms from two distinct promoters: msrA1 (mitochondrial targeting), and msrA2/3 (cytosolic and nuclear localization). siRNA-mediated silencing of MSRA increases oxidative damage susceptibility in RPE cells. 5'RACE cloning of transcripts; promoter analysis; subcellular localization of isoform-GFP fusions; siRNA knockdown; oxidative stress cell viability assays Experimental eye research High 16364291
2008 Mammals reduce methionine-S-sulfoxide via an MsrA-dependent pathway; MsrA knockout mice accumulate methionine-R-sulfoxide in plasma (but not S-sulfoxide), demonstrating MsrA is specifically required for reduction of the S-epimer of free methionine sulfoxide in vivo. MsrA knockout mouse; SK-Hep1 cell culture on methionine sulfoxides; plasma sulfoxide measurement; yeast free methionine-R-sulfoxide reductase complementation The Journal of biological chemistry High 18697736
2006 Invariant Glu-94, Tyr-82, and Tyr-134 in the MsrA active site (Neisseria meningitidis) are required for catalysis of the reductase step: they stabilize the sulfurane transition state and lower the pKa of the catalytic Cys-51, which forms a sulfenic acid intermediate upon substrate reduction. Site-directed mutagenesis; kinetic analysis; mechanistic characterization of reductase step The Journal of biological chemistry High 17062561
2008 MsrA knockout mice display abnormal dopamine levels (elevated at younger ages, decreased at 16 months) and impaired locomotor behavior, suggesting MsrA regulates dopamine signaling pathways, correlated with age-dependent changes in tyrosine hydroxylase activating protein expression. MsrA knockout mouse; dopamine measurements in striatal brain regions; amphetamine response testing; locomotor activity assays; tyrosine hydroxylase expression analysis Free radical biology & medicine Medium 18466776
2008 In Drosophila, MsrA is induced by ecdysone via the EcR-USP complex; this hormonal induction is required for ecdysone-mediated protection against H2O2-induced oxidative stress. EcR-deficient cells lose both ecdysone induction of MsrA and H2O2 resistance. Ecdysone treatment of Kc cells; RT-PCR; H2O2 viability assay; EcR-knockout cell line comparison Biochemical and biophysical research communications Medium 17239346
2008 The human MSRA gene is regulated by two distinct promoters: promoter 1 (upstream, drives the mitochondrial msrA1 isoform) and promoter 2 (downstream, drives cytosolic/nuclear msrA2/3 isoforms). Both promoters are partially regulated by all-trans retinoic acid via RARA and other RARs. Promoter-reporter assays; deletion analysis; retinoic acid treatment; RAR siRNA knockdown; cell-line-specific expression analysis Genomics Medium 18845237
2009 MsrA co-immunoprecipitates with cytochrome c and four of the five mitochondrial electron transport chain complexes. MsrA repairs oxidized methionines (Met65 and Met80) in cytochrome c, restoring cytochrome c oxidase activity and reducing cytochrome c peroxidase activity. MsrA deletion causes accumulation and degradation of oxidized cytochrome c in lens. Co-immunoprecipitation; cyanogen bromide cleavage for oxidized methionine identification; in vitro MsrA repair assay with activity measurements; mass spectrometry; MsrA knockout mouse lens analysis Molecular vision High 19461988
2009 Methionine oxidation of alpha-crystallin (Met138 of alphaA, Met68 of alphaB) abolishes its chaperone activity. MsrA reduces these methionine sulfoxides and restores chaperone function. Deletion of MsrA in mice results in increased PMSO-alpha-crystallin accumulation in lens. In vitro oxidation and MsrA repair of alpha-crystallin; CNBr cleavage and mass spectrometry for methionine sulfoxide identification; chaperone activity assay (light scattering); MsrA knockout mouse lens analysis Biochimica et biophysica acta High 19733220
2015 Mitochondria-targeted MsrA overexpression, but not cytosolic MsrA, preserves insulin sensitivity in diet-induced obese mice without altering obesity itself. The protective effect is associated with activation of AMPK signaling, suggesting a mechanism by which mitochondrial protein methionine repair modulates metabolic homeostasis. Transgenic mouse models with compartment-specific MsrA overexpression (TgMito vs TgCyto); high-fat diet feeding; glucose tolerance and insulin sensitivity tests; AMPK activity measurements PloS one Medium 26448611
2017 Archaeal MsrA catalyzes ubiquitin-like (Ubl) protein modification in the presence of the Ubl-activating E1 enzyme UbaA and mild oxidant (DMSO), using the same active site as methionine sulfoxide reduction. This Ubl modification activity is distinct from and antagonized by the methionine sulfoxide reductase activity; MsrA-dependent Ubl conjugates include Orc3 and Cdc48d proteins involved in DNA replication and protein remodeling. In vitro Ubl modification assay; LC-MS/MS identification of conjugates; active-site mutant analysis; DMSO-dependent activity assay; reductant inhibition studies mBio Medium 28874471
2018 Mammalian MsrA mediates ubiquitination of 14-3-3 zeta protein in brain and promotes binding of 14-3-3 proteins to alpha-synuclein; it also enhances ubiquitination and phosphorylation of Ser129 of alpha-synuclein. MsrA competes for ubiquitin capture using the same active site as methionine sulfoxide binding. Co-immunoprecipitation; ubiquitination assays in brain tissue; phosphorylation analysis; MsrA knockout mouse brain comparison; active-site competition assays Free radical biology & medicine Medium 30096435
2020 MsrA interacts with Jab1/CSN5 and enhances its deneddylase activity (removal of Nedd8 from Cullin-1). This interaction increases Jab1 binding affinity to P27, promoting P27 ubiquitination and degradation. MsrA ablation causes dramatic increase in P27 expression. Co-immunoprecipitation; deneddylase activity assay; P27 level measurement in MsrA-knockout cells; Cullin-1 neddylation state analysis Antioxidants (Basel, Switzerland) Medium 32456285
2007 A novel splice variant of MSRA (msrA2a) exists in rat vascular smooth muscle cells, encoding a mitochondrially targeted isoform with confirmed enzymatic activity on methionine sulfoxide substrate. Endogenous MSRA immunoreactivity in VSMCs is exclusively mitochondrial. RT-PCR and sequence analysis of splice variants; recombinant protein expression and in vitro activity assay; immunofluorescence localization Free radical research Medium 17907003
2018 Drosophila MSRA lacks methionine oxidase activity despite having an active site sequence identical to mammalian MSRA. The Drosophila enzyme cannot complete the third step of the oxidase mechanism (disulfide exchange at carboxy-terminal cysteine to regenerate the active site), though it performs the reductase reaction and first two steps normally. Recombinant Drosophila MSRA expression; in vitro methionine sulfoxide reductase and oxidase assays; mechanistic dissection of active-site sulfenic acid chemistry; carboxy-terminal domain analysis Free radical biology & medicine High 30529269
2024 S-Methyl-L-cysteine (SMLC) acts as a methionine analog substrate for MsrA, enabling scavenging of free radicals. SMLC activates MsrA which reduces oxidized CaMKII (ox-CaMKII) and inhibits p38 MAPK phosphorylation, protecting against Ang II-induced atrial remodeling. MsrA knockdown abolishes the protective effects of SMLC, placing MsrA upstream of the p38 MAPK pathway. In vivo Ang II mouse model; siRNA knockdown of MsrA in HL-1 cells; RNA sequencing; Western blotting for ox-CaMKII and p38 MAPK; SB203580 (p38 inhibitor) rescue experiment Food & function Medium 39157962
2016 Cytosolic MsrA overexpression (TgCyto) reduces age-related death rate in female mice by Gompertz analysis but does not extend median lifespan; mitochondrial MsrA overexpression improves insulin sensitivity in aged females, demonstrating subcellular localization-dependent effects on aging and metabolic phenotypes. Transgenic mouse models with cytosol- and mitochondria-targeted MsrA; Gompertz and log-rank lifespan analysis; glucose tolerance and insulin sensitivity tests Redox biology Medium 27821326
2025 Iron coordinates to conserved E203-xx-H206 motifs to multimerize, stabilize, and enzymatically activate MSRA. Activated MSRA maintains reduced methionines near the ATP-binding site of Protein Kinase A (PKA), thereby facilitating PKA-driven adipose browning. MsrA deletion in PDA mouse models impairs WAT browning and improves survival of tumor-bearing animals. Iron-binding mutagenesis; structural/biophysical characterization of MSRA multimers; PKA methionine oxidation state analysis; MsrA knockout mouse model of PDA; WAT browning and cachexia measurements bioRxivpreprint Medium bio_10.1101_2025.07.16.664180

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. Proceedings of the National Academy of Sciences of the United States of America 543 11606777
2000 Identification and characterization of a putative active site for peptide methionine sulfoxide reductase (MsrA) and its substrate stereospecificity. The Journal of biological chemistry 156 10799493
2008 Mitochondrial function and redox control in the aging eye: role of MsrA and other repair systems in cataract and macular degenerations. Experimental eye research 152 18588875
1999 The minimal gene set member msrA, encoding peptide methionine sulfoxide reductase, is a virulence determinant of the plant pathogen Erwinia chrysanthemi. Proceedings of the National Academy of Sciences of the United States of America 129 9927663
2002 The outer membrane localization of the Neisseria gonorrhoeae MsrA/B is involved in survival against reactive oxygen species. Proceedings of the National Academy of Sciences of the United States of America 108 12096194
2001 Peptide methionine sulfoxide reductase (MsrA) is a virulence determinant in Mycoplasma genitalium. Journal of bacteriology 93 11544227
2003 Subcellular localization of methionine sulphoxide reductase A (MsrA): evidence for mitochondrial and cytosolic isoforms in rat liver cells. The Biochemical journal 91 12693988
2002 Mitochondrial targeting of the human peptide methionine sulfoxide reductase (MSRA), an enzyme involved in the repair of oxidized proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 91 12039877
2017 Assessing the Risk of Sarcopenia in the Elderly: The Mini Sarcopenia Risk Assessment (MSRA) Questionnaire. The journal of nutrition, health & aging 85 28537342
2003 Msr(A) and related macrolide/streptogramin resistance determinants: incomplete transporters? International journal of antimicrobial agents 80 13678826
2006 Molecular evolution of peptide methionine sulfoxide reductases (MsrA and MsrB): on the early development of a mechanism that protects against oxidative damage. Journal of molecular evolution 66 17180746
2004 Methionine sulfoxide reductase A (MsrA) deficiency affects the survival of Mycobacterium smegmatis within macrophages. Journal of bacteriology 63 15150247
1995 Identification of a chromosomally encoded ABC-transport system with which the staphylococcal erythromycin exporter MsrA may interact. Gene 63 7883194
2019 Baicalin Inhibits Biofilm Formation and the Quorum-Sensing System by Regulating the MsrA Drug Efflux Pump in Staphylococcus saprophyticus. Frontiers in microbiology 62 31921008
2004 The peptide methionine sulfoxide reductases, MsrA and MsrB (hCBS-1), are downregulated during replicative senescence of human WI-38 fibroblasts. FEBS letters 61 14759519
2005 Overexpression of MsrA protects WI-38 SV40 human fibroblasts against H2O2-mediated oxidative stress. Free radical biology & medicine 60 16257642
2003 Characteristic expression of three genes, msr(A), mph(C) and erm(Y), that confer resistance to macrolide antibiotics on Staphylococcus aureus. FEMS microbiology letters 59 12670694
2008 Spread of invasive Spanish Staphylococcus aureus spa-type t067 associated with a high prevalence of the aminoglycoside-modifying enzyme gene ant(4')-Ia and the efflux pump genes msrA/msrB. The Journal of antimicrobial chemotherapy 51 18948410
2009 Structural and kinetic analysis of an MsrA-MsrB fusion protein from Streptococcus pneumoniae. Molecular microbiology 46 19400786
2008 Contribution of the stereospecific methionine sulphoxide reductases MsrA and MsrB to oxidative and nitrosative stress resistance in the food-borne pathogen Campylobacter jejuni. Microbiology (Reading, England) 46 18667555
2007 MsrA protects cardiac myocytes against hypoxia/reoxygenation induced cell death. Biochemical and biophysical research communications 46 18083115
2008 MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels. Free radical biology & medicine 44 18466776
2008 Mammals reduce methionine-S-sulfoxide with MsrA and are unable to reduce methionine-R-sulfoxide, and this function can be restored with a yeast reductase. The Journal of biological chemistry 44 18697736
2007 Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma. BMC cancer 44 17784942
2005 Gene structure, localization and role in oxidative stress of methionine sulfoxide reductase A (MSRA) in the monkey retina. Experimental eye research 41 16364291
1996 Minimal functional system required for expression of erythromycin resistance by msrA in Staphylococcus aureus RN4220. Gene 41 8996099
2001 Uptake of fibrillar beta-amyloid by microglia isolated from MSR-A (type I and type II) knockout mice. Neuroreport 38 11338182
2006 Staphylococcus efflux msr(A) gene characterized in Streptococcus, Enterococcus, Corynebacterium, and Pseudomonas isolates. Antimicrobial agents and chemotherapy 36 16495276
2011 Implications of central obesity-related variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on quantitative metabolic traits in adult Danes. PloS one 35 21674055
2017 Replication and characterization of CADM2 and MSRA genes on human behavior. Heliyon 34 28795158
2014 Association study of common polymorphisms in MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 and OLFM4 genes with obesity-related traits among Portuguese children. Journal of human genetics 34 24670271
2009 Deletion of mouse MsrA results in HBO-induced cataract: MsrA repairs mitochondrial cytochrome c. Molecular vision 34 19461988
2010 Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population. Journal of human genetics 32 20703240
2009 Methionine sulfoxide reductase A (MsrA) restores alpha-crystallin chaperone activity lost upon methionine oxidation. Biochimica et biophysica acta 29 19733220
2006 Characterization of the amino acids from Neisseria meningitidis MsrA involved in the chemical catalysis of the methionine sulfoxide reduction step. The Journal of biological chemistry 29 17062561
2012 Protective effects of taurine against oxidative stress in the heart of MsrA knockout mice. Journal of cellular biochemistry 28 22740506
2007 Prolonged selenium-deficient diet in MsrA knockout mice causes enhanced oxidative modification to proteins and affects the levels of antioxidant enzymes in a tissue-specific manner. Free radical research 28 17364942
2019 Genetic variants in RUNX3, AMD1 and MSRA in the methionine metabolic pathway and survival in nonsmall cell lung cancer patients. International journal of cancer 27 30650190
2019 The Neisseria gonorrhoeae Methionine Sulfoxide Reductase (MsrA/B) Is a Surface Exposed, Immunogenic, Vaccine Candidate. Frontiers in immunology 27 30787927
2020 MsrA Suppresses Inflammatory Activation of Microglia and Oxidative Stress to Prevent Demyelination via Inhibition of the NOX2-MAPKs/NF-κB Signaling Pathway. Drug design, development and therapy 26 32308370
2017 Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea. mBio 24 28874471
2016 Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice. Redox biology 24 27821326
2015 Enhancing stress tolerance by overexpression of a methionine sulfoxide reductase A (MsrA) gene in Pleurotus ostreatus. Applied microbiology and biotechnology 21 25573474
2010 Methionine sulfoxide reductase A (MsrA) protects cultured mouse embryonic stem cells from H2O2-mediated oxidative stress. Journal of cellular biochemistry 21 20506347
2007 Ecdysone induction of MsrA protects against oxidative stress in Drosophila. Biochemical and biophysical research communications 21 17239346
2015 Methionine sulfoxide reductase A (MsrA) contributes to Salmonella Typhimurium survival against oxidative attack of neutrophils. Immunobiology 19 26224245
2006 Protein-carbonyl accumulation in the non-replicative senescence of the methionine sulfoxide reductase A (msrA) knockout yeast strain. Amino acids 19 17077964
2022 Luteolin increases susceptibility to macrolides by inhibiting MsrA efflux pump in Trueperella pyogenes. Veterinary research 18 35012652
2015 MsrA Overexpression Targeted to the Mitochondria, but Not Cytosol, Preserves Insulin Sensitivity in Diet-Induced Obese Mice. PloS one 18 26448611
2012 Variation in MSRA modifies risk of neonatal intestinal obstruction in cystic fibrosis. PLoS genetics 18 22438829
2015 PEP-1-MsrA ameliorates inflammation and reduces atherosclerosis in apolipoprotein E deficient mice. Journal of translational medicine 17 26410585
2013 The sRNA RyhB regulates the synthesis of the Escherichia coli methionine sulfoxide reductase MsrB but not MsrA. PloS one 17 23671689
2009 Differential expression of the antioxidant repair enzyme methionine sulfoxide reductase (MSRA and MSRB) in human skin. The American Journal of dermatopathology 17 19542914
2012 Methionine sulfoxide reductase A (MsrA) deficient Mycoplasma genitalium shows decreased interactions with host cells. PloS one 15 22558404
2024 S-Methyl-L-cysteine targeting MsrA attenuates Ang II-induced oxidative stress and atrial remodeling via the p38 MAPK signaling pathway. Food & function 14 39157962
2019 Identification of MsrA homologues for the preparation of (R)-sulfoxides at high substrate concentrations. Organic & biomolecular chemistry 14 30860233
2010 Identification of the oxidative stress-related gene MSRA as a rheumatoid arthritis susceptibility locus by genome-wide pathway analysis. Arthritis and rheumatism 14 20617525
2008 Retinoic acid regulates the human methionine sulfoxide reductase A (MSRA) gene via two distinct promoters. Genomics 14 18845237
2002 Peptide methionine sulfoxide reductase (MsrA) is not a major virulence determinant for the oral pathogen Actinobacillus actinomycetemcomitans. Microbiology (Reading, England) 14 12427959
2016 Essential Role of the Linker Region in the Higher Catalytic Efficiency of a Bifunctional MsrA-MsrB Fusion Protein. Biochemistry 13 27551953
2016 A rapid loop-mediated isothermal amplification (LAMP) method for detection of the macrolide-streptogramin type B resistance gene msrA in Staphylococcus aureus. Journal of global antimicrobial resistance 12 27607914
2015 Methionine sulfoxide reductase A (MsrA) associated with bipolar I disorder and executive functions in A Han Chinese population. Journal of affective disorders 12 26117066
2023 NorA, Tet(K), MepA, and MsrA Efflux Pumps in Staphylococcus aureus, their Inhibitors and 1,8-Naphthyridine Sulfonamides. Current pharmaceutical design 11 36515045
2022 Metabolic benefits of methionine restriction in adult mice do not require functional methionine sulfoxide reductase A (MsrA). Scientific reports 10 35332198
2007 Identification of a new functional splice variant of the enzyme methionine sulphoxide reductase A (MSRA) expressed in rat vascular smooth muscle cells. Free radical research 10 17907003
2023 Sexually dimorphic effects of methionine sulfoxide reductase A (MsrA) on murine longevity and health span during methionine restriction. GeroScience 9 37391679
2021 KRAS, YWHAE, SP1 and MSRA as biomarkers in endometrial cancer. Translational cancer research 9 35116456
2018 Methionine sulfoxide reductase A (MsrA) mediates the ubiquitination of 14-3-3 protein isotypes in brain. Free radical biology & medicine 9 30096435
2016 Salmonella Typhimurium methionine sulfoxide reductase A (MsrA) prefers TrxA in repairing methionine sulfoxide. Preparative biochemistry & biotechnology 9 27191346
2022 A Novel Small RNA, DsrO, in Deinococcus radiodurans Promotes Methionine Sulfoxide Reductase (msrA) Expression for Oxidative Stress Adaptation. Applied and environmental microbiology 8 35575549
2020 Methionine sulfoxide reductase A (MsrA) modulates cells and protects against Mycoplasma genitalium induced cytotoxicity. Free radical biology & medicine 8 32222467
2020 The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function. Antioxidants (Basel, Switzerland) 8 32456285
2018 Drosophila methionine sulfoxide reductase A (MSRA) lacks methionine oxidase activity. Free radical biology & medicine 7 30529269
2015 ClpP-independent function of ClpX interferes with telithromycin resistance conferred by Msr(A) in Staphylococcus aureus. Antimicrobial agents and chemotherapy 6 25801573
2012 MSRA polymorphism is associated with the risk of rheumatoid arthritis in a Chinese population. Scandinavian journal of rheumatology 5 23244167
2022 Recombinant Humanized IgG1 Antibody Protects against oxLDL-Induced Oxidative Stress and Apoptosis in Human Monocyte/Macrophage THP-1 Cells by Upregulation of MSRA via Sirt1-FOXO1 Axis. International journal of molecular sciences 4 36233020
2015 Regulation of expression of sodA and msrA genes of Corynebacterium glutamicum in response to oxidative and radiative stress. Genetics and molecular research : GMR 4 25867357
2024 Polygenic markers of survival and longevity in the antioxidant genes PON1, PON2, MTHFR, MSRA, SOD1, NQO1, and CAT in a 20-year follow-up study in the population from the Volga-Ural region. Gene 3 38679184
2021 Structural Insights into a Bifunctional Peptide Methionine Sulfoxide Reductase MsrA/B Fusion Protein from Helicobacter pylori. Antioxidants (Basel, Switzerland) 3 33807684
2012 Mutations in msrA and msrB, encoding epimer-specific methionine sulfoxide reductases, affect expression of glycerol-catabolic operons in Enterococcus faecalis differently. Microbiology (Reading, England) 3 23258264
2021 Molecular Expression of Bioactive Recombinant Methionine Sulfoxide Reductase A (MsrA). Protein and peptide letters 2 32586239
2015 Essential role of the C-terminal helical domain in active site formation of selenoprotein MsrA from Clostridium oremlandii. PloS one 2 25692691
2011 The protein truncation caused by fusion of PEP-1 peptide and protective roles of transduced PEP-1-MsrA in skin cells. BMB reports 2 21524351
2025 ApoE Mimetic Peptide-MsrA Fusion Protein Restores HDL Function and Ameliorates Atherosclerosis via Circulatory Redox Remodeling in SR-BI Deficient Mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 40888010
2023 Mycobacterium smegmatis secreting methionine sulfoxide reductase A (MsrA) modulates cellular processes in mouse macrophages. Biochimie 1 36809827
2023 Sulfur Amino Acid Restriction alters mitochondrial function depending on tissue, sex, and Methionine sulfoxide reductase A (MsrA) status. Research square 1 38196647
2013 Molecular cloning and characterisation of the methionine sulphoxide reductase A (msrA) gene locus in Campylobacter lari organisms. British journal of biomedical science 1 24400424
2006 [The frequency of the occurrence of genes ermA, ermB, ermC and msrA/B among methicillin-resistant Staphylococcus aureus strains resistant to erythromycin]. Medycyna doswiadczalna i mikrobiologia 1 17340992
1993 MSR--a program for kinetic analysis of enzyme modification data on PC. Computers in biology and medicine 1 8375153
2026 Frequency of macrolide resistance gene msrA in clinically isolated erythromycin resistant Staphylococcus aureus strains from a tertiary care setting in Sindh, Pakistan. Pakistan journal of pharmaceutical sciences 0 41879410
2026 Discovery, evolution, and environmental co-selection of novel msrA-harboring plasmids in multidrug-resistant Staphylococcus from retail foods. International journal of food microbiology 0 41935458
2026 Evolution and transmission landscape of the staphylococcal msrA gene mediating resistance to 14-membered macrolides and type B streptogramins. Frontiers in microbiology 0 42100691
2025 Single-Cell Nuclear Sequencing Atlas Revealed the Induction of Parkinson's Disease by RELN+ Neuron 3 and the Gene Regulatory Network of MSRA. Current medicinal chemistry 0 38561620
2025 Novel Visual Perspective for Tracking of Larval Development, Aging and Antiaging Drugs Screening by Fluorescent Sensing MsrA. Analytical chemistry 0 40459335
2021 Variability in the antioxidant MSRA gene affects the psychopathology of patients with anorexia nervosa. Acta neuropsychiatrica 0 34396949

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