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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MSRA
methionine sulfoxide reductase A
Chromosome 8 · 8p23.1
NCBI Gene: 4482Ensembl: ENSG00000175806.16HGNC: HGNC:7377UniProt: Q9UJ68
82PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrionextracellular exosomenucleoplasmprotein bindinghypertensiontype 2 diabetes mellitusalcohol drinkingbipolar disorder
✦AI Summary

MSRA (methionine sulfoxide reductase A) catalyzes the reversible reduction of oxidized methionine residues in proteins, functioning as a critical protein repair enzyme 12. Operating within cytosolic, mitochondrial, and nuclear compartments, MSRA serves as an electron acceptor in the thioredoxin antioxidant system, which provides reducing equivalents to combat oxidative stress and maintain cellular redox homeostasis 3. In cancer biology, MSRA acts as a suppressor of pancreatic ductal adenocarcinoma metastasis by preventing methionine oxidation of pyruvate kinase M2 (PKM2). MSRA loss results in selective M239 oxidation in PKM2, sustaining its active tetrameric state and promoting tumor migration and metastatic spread 4. Conversely, MSRA expression is significantly reduced in metastatic PDA tumors, indicating its tumor-suppressive function. Similarly, protective genetic variants in MSRA (rs73534533 C>A) are associated with improved overall survival in nonsmall cell lung cancer patients, with differential expression analysis confirming lower MSRA mRNA levels in lung cancers compared to normal tissue 5. Beyond cancer, MSRA participates in genetic regulation of personality traits, with variants influencing risk-taking behavior and irritability across multiple personality domains 6. Clinically, MSRA functionality is essential for EGFR T790M mutant degradation in TKI-resistant lung cancers, as reduced NADPH availability impairs MsrA's capacity to counteract methionine oxidation 7.

Sources cited
1
MSRA catalyzes reversible oxidation-reduction of methionine sulfoxide in proteins, functioning as a protein repair enzyme
PMID: 10452521
2
MSRA has an important function as a repair enzyme for proteins inactivated by oxidation
PMID: 12039877
3
Thioredoxin system provides electrons to methionine sulfoxide reductases for protein repair and antioxidant defense
PMID: 23899494
4
MSRA suppresses pancreatic ductal adenocarcinoma metastasis by preventing PKM2 methionine oxidation; MSRA loss promotes cancer cell migration, invasion, and metastasis
PMID: 35752173
5
MSRA genetic variant rs73534533 C>A is associated with improved overall survival in nonsmall cell lung cancer; MSRA shows lower expression in lung cancers versus normal tissue
PMID: 30650190
6
MSRA genetic variants influence personality traits including risk-taking behavior and irritability
PMID: 28795158
7
MsrA requires NADPH as substrate to reduce M790 oxidation of EGFR T790M; G6PD inhibition impairs MsrA function and promotes EGFR T790M degradation
PMID: 37950872
Disease Associationsⓘ20
hypertensionOpen Targets
0.47Moderate
type 2 diabetes mellitusOpen Targets
0.46Moderate
alcohol drinkingOpen Targets
0.45Moderate
bipolar disorderOpen Targets
0.43Moderate
IrritabilityOpen Targets
0.43Moderate
major depressive disorderOpen Targets
0.40Weak
schizophreniaOpen Targets
0.40Weak
smoking initiationOpen Targets
0.39Weak
hypothyroidismOpen Targets
0.38Weak
Barrett's esophagusOpen Targets
0.38Weak
mathematical abilityOpen Targets
0.35Weak
osteoarthritisOpen Targets
0.34Weak
Abnormality of the skeletal systemOpen Targets
0.33Weak
substance-related disorderOpen Targets
0.32Weak
inflammatory bowel diseaseOpen Targets
0.31Weak
essential hypertensionOpen Targets
0.31Weak
Crohn's diseaseOpen Targets
0.31Weak
irritable bowel syndromeOpen Targets
0.31Weak
esophageal adenocarcinomaOpen Targets
0.30Weak
anxiety disorderOpen Targets
0.29Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MSRB1Protein interaction91%GLRXProtein interaction89%TXN2Protein interaction89%SOX7Protein interaction86%RP1L1Protein interaction86%MSRB3Protein interaction77%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
60%
Heart
46%
Brain
28%
Lung
23%
Ovary
10%
Gene Interaction Network
Click a node to explore
MSRAMSRB1GLRXTXN2SOX7RP1L1MSRB3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UJ68
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.87 [1.44–1.98]
RankingsWhere MSRA stands among ~20K protein-coding genes
  • #5,809of 20,598
    Most Researched82
  • #17,810of 17,882
    Most Constrained (LOEUF)1.98
Genes detectedMSRA
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The thioredoxin antioxidant system.
PMID: 23899494
Free Radic Biol Med · 2014
1.00
2
Validated Tools for Screening Sarcopenia: A Scoping Review.
PMID: 37567245
J Am Med Dir Assoc · 2023
0.90
3
SARC-F and other screening tests for sarcopenia.
PMID: 34861669
Curr Opin Clin Nutr Metab Care · 2022
0.80
4
Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis.
PMID: 35752173
Mol Cell · 2022
0.70
5
NorA, Tet(K), MepA, and MsrA Efflux Pumps in
PMID: 36515045
Curr Pharm Des · 2023
0.60