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    MSRA methionine sulfoxide reductase A [ Homo sapiens (human) ]

    Gene ID: 4482, updated on 2-Nov-2024

    Summary

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    Official Symbol
    MSRAprovided by HGNC
    Official Full Name
    methionine sulfoxide reductase Aprovided by HGNC
    Primary source
    HGNC:HGNC:7377
    See related
    Ensembl:ENSG00000175806 MIM:601250; AllianceGenome:HGNC:7377
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PMSR
    Summary
    This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
    Expression
    Broad expression in kidney (RPKM 12.0), bone marrow (RPKM 3.1) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MSRA in Genome Data Viewer
    Location:
    8p23.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (10054292..10428891)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (9310290..9686356, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (9911802..10286401)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105379235 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18909 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18910 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:9912619-9913205 Neighboring gene uncharacterized LOC124901885 Neighboring gene MSRA divergent transcript Neighboring gene uncharacterized LOC124901886 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26989 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:10109393-10109588 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26990 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26991 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:10191981-10192805 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:10191156-10191980 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr8:10194133-10194989 Neighboring gene transmembrane protein 126A pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr8:10214030-10214233 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:10273265-10274127 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr8:10275622-10276144 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:10280427-10280927 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:10282861-10283372 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:10283373-10283882 Neighboring gene uncharacterized LOC124901887 Neighboring gene long intergenic non-protein coding RNA 3022 Neighboring gene RNA, U6 small nuclear 729, pseudogene Neighboring gene serine protease 52, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Association study of common polymorphisms in MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 and OLFM4 genes with obesity-related traits among Portuguese children. Albuquerque D, et al. J Hum Genet, 2014 Jun. PMID 24670271
    2. Identification of the oxidative stress-related gene MSRA as a rheumatoid arthritis susceptibility locus by genome-wide pathway analysis. Martín JE, et al. Arthritis Rheum, 2010 Nov. PMID 20617525
    3. Focus on Molecules: methionine sulfoxide reductase A. Kantorow M, et al. Exp Eye Res, 2012 Jul. PMID 20888813, Free PMC Article
    4. Methionine sulfoxide reductase A down-regulation in human breast cancer cells results in a more aggressive phenotype. De Luca A, et al. Proc Natl Acad Sci U S A, 2010 Oct 26. PMID 20937881, Free PMC Article
    5. A genome-wide association study for quantitative traits in schizophrenia in China. Ma X, et al. Genes Brain Behav, 2011 Oct. PMID 21679298

    See all (81) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients.
      Title: Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients.
    2. Methionine sulfoxide reductase A (MsrA) modulates cells and protects against Mycoplasma genitalium induced cytotoxicity.
      Title: Methionine sulfoxide reductase A (MsrA) modulates cells and protects against Mycoplasma genitalium induced cytotoxicity.
    3. Three SNPs (RUNX3 rs7553295 G > T, AMD1 rs1279590 G > A and MSRA rs73534533 C > A) were replicated in the validation dataset, and their meta-analysis showed an adjusted hazards ratio [HR] of 0.82 [95% confidence interval (CI) =0.75-0.89] and pmeta = 2.86 x 10(-6) , 0.81 (0.73-0.91) and pmeta = 4.63 x 10(-4) , and 0.77 (0.68-0.89) and pmeta = 2.07 x 10(-4) , respectively).
      Title: Genetic variants in RUNX3, AMD1 and MSRA in the methionine metabolic pathway and survival in nonsmall cell lung cancer patients.
    4. myristoylated MSRA is a late endosomal protein that may play a role in lipid metabolism or may protect endosomal proteins from oxidative damage.
      Title: Myristoylated methionine sulfoxide reductase A is a late endosomal protein.
    5. Data show that miR-193b, by directly targeting focal adhesion kinase (FAK), CRK-like proto-oncogene (CRKL), and methionine sulfoxide reductase A (MSRA), regulates focal adhesion signaling and ROS signaling, which play pivotal roles in liposarcomagenesis and adipogenic differentiation.
      Title: miR-193b-Regulated Signaling Networks Serve as Tumor Suppressors in Liposarcoma and Promote Adipogenesis in Adipose-Derived Stem Cells.
    6. this study we have identified, for the first time, compounds structurally related to the natural products fusaricidins that markedly activate recombinant bovine and human MsrA and human MsrB.
      Title: Identification of activators of methionine sulfoxide reductases A and B.
    7. The association of MsrA haplotypes with executive functions indicated that MsrA is associated with executive function defects in bipolar I disorder patients.
      Title: Methionine sulfoxide reductase A (MsrA) associated with bipolar I disorder and executive functions in A Han Chinese population.
    8. Silencing the expression of the main Msr elements-MsrA, MsrB1, or MsrB2 exacerbates sensitivity toward oxidative stress.
      Title: Proteome alteration in oxidative stress-sensitive methionine sulfoxide reductase-silenced HEK293 cells.
    9. ARD1 has a crucial role in the cellular response to oxidative stress as a bona fide regulator of MSRA.
      Title: Arrest defective 1 regulates the oxidative stress response in human cells and mice by acetylating methionine sulfoxide reductase A.
    10. The functional MSRA rs10903323 G/A polymorphism is associated with coronary artery disease development.
      Title: Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a Chinese population.
    Submit: New GeneRIF Correction See all GeneRIFs (42)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study for quantitative traits in schizophrenia in China.
    EBI GWAS Catalog
    A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French Population.
    EBI GWAS Catalog
    Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study.
    EBI GWAS Catalog
    Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100.
    EBI GWAS Catalog
    Genetic variants associated with disordered eating.
    EBI GWAS Catalog
    Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
    EBI GWAS Catalog
    Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.
    EBI GWAS Catalog
    Genome-wide association study of blood pressure and hypertension.
    EBI GWAS Catalog
    Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif downregulates the expression of methionine sulfoxide reductase A (MSRA) in Vif-expression T cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables L-methionine-(S)-S-oxide reductase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables peptide-methionine (S)-S-oxide reductase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables peptide-methionine (S)-S-oxide reductase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to oxidative stress IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in methionine metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein modification process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein repair TAS
    Traceable Author Statement
    more info
    		  
    involved_in response to oxidative stress TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in actin cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in midbody IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    mitochondrial peptide methionine sulfoxide reductase
    Names
    cytosolic methionine-S-sulfoxide reductase
    peptide Met(O) reductase
    peptide met (O) reductase
    peptide-methionine (S)-S-oxide reductase
    NP_001129142.1
    NP_001129143.1
    NP_001186658.1
    NP_036463.1
    XP_011542124.1
    XP_011542125.1
    XP_016868939.1
    XP_016868940.1
    XP_024302930.1
    XP_054188220.1
    XP_054188221.1
    XP_054188222.1
    XP_054216474.1
    XP_054216475.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001135670.3 → NP_001129142.1  mitochondrial peptide methionine sulfoxide reductase isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (b) that is shorter than isoform a.
      Source sequence(s)
      AC023385, AC034111, AC112673
      Consensus CDS
      CCDS47798.1
      UniProtKB/Swiss-Prot
      Q9UJ68
      Related
      ENSP00000410912.2, ENST00000441698.6
      Conserved Domains (1) summary
      cl00366
      Location:30 → 192
      PMSR; Peptide methionine sulfoxide reductase

    2. NM_001135671.3 → NP_001129143.1  mitochondrial peptide methionine sulfoxide reductase isoform c

      See identical proteins and their annotated locations for NP_001129143.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (c) has a shorter and distinct N-terminus, compared to isoform a.
      Source sequence(s)
      AC023385, AC079200, AC112673
      Consensus CDS
      CCDS47799.1
      UniProtKB/Swiss-Prot
      Q9UJ68
      Related
      ENSP00000371930.5, ENST00000382490.9
      Conserved Domains (1) summary
      PRK00058
      Location:1 → 189
      PRK00058; methionine sulfoxide reductase A; Provisional

    3. NM_001199729.3 → NP_001186658.1  mitochondrial peptide methionine sulfoxide reductase isoform d

      See identical proteins and their annotated locations for NP_001186658.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains alternate 5' exon structure, and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (d) is shorter at the N-terminus, compared to isoform a.
      Source sequence(s)
      AC023385, AC079200, AC112673
      Consensus CDS
      CCDS56522.1
      UniProtKB/Swiss-Prot
      Q9UJ68
      Related
      ENSP00000436839.1, ENST00000528246.5
      Conserved Domains (1) summary
      PRK00058
      Location:2 → 166
      PRK00058; methionine sulfoxide reductase A; Provisional

    4. NM_012331.5 → NP_036463.1  mitochondrial peptide methionine sulfoxide reductase isoform a precursor

      See identical proteins and their annotated locations for NP_036463.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      AC023385, AC034111, AC079200, AC112673
      Consensus CDS
      CCDS5975.1
      UniProtKB/Swiss-Prot
      E9PAS8, Q52TC4, Q549N4, Q66MI7, Q9UJ68
      Related
      ENSP00000313921.4, ENST00000317173.9
      Conserved Domains (1) summary
      PRK00058
      Location:30 → 232
      PRK00058; methionine sulfoxide reductase A; Provisional

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      10054292..10428891
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011543822.3 → XP_011542124.1  mitochondrial peptide methionine sulfoxide reductase isoform X1

      UniProtKB/TrEMBL
      E5RIA9
      Conserved Domains (1) summary
      cl00366
      Location:30 → 182
      PMSR; Peptide methionine sulfoxide reductase

    2. XM_011543823.3 → XP_011542125.1  mitochondrial peptide methionine sulfoxide reductase isoform X2

      UniProtKB/TrEMBL
      E5RIA9
      Conserved Domains (1) summary
      cl00366
      Location:30 → 181
      PMSR; Peptide methionine sulfoxide reductase

    3. XM_024447162.2 → XP_024302930.1  mitochondrial peptide methionine sulfoxide reductase isoform X5

      Conserved Domains (1) summary
      cl00366
      Location:30 → 110
      PMSR; Peptide methionine sulfoxide reductase

    4. XM_017013451.3 → XP_016868940.1  mitochondrial peptide methionine sulfoxide reductase isoform X4

      UniProtKB/TrEMBL
      B7Z694

    5. XM_017013450.3 → XP_016868939.1  mitochondrial peptide methionine sulfoxide reductase isoform X3

      UniProtKB/Swiss-Prot
      Q9UJ68
      Conserved Domains (1) summary
      PRK00058
      Location:2 → 166
      PRK00058; methionine sulfoxide reductase A; Provisional

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_018654717.1 Reference GRCh38.p14 PATCHES

      Range
      2918137..3294116 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054332247.1 → XP_054188222.1  mitochondrial peptide methionine sulfoxide reductase isoform X3

    2. XM_054332245.1 → XP_054188220.1  mitochondrial peptide methionine sulfoxide reductase isoform X1

    3. XM_054332246.1 → XP_054188221.1  mitochondrial peptide methionine sulfoxide reductase isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      9310290..9686356 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360500.1 → XP_054216475.1  mitochondrial peptide methionine sulfoxide reductase isoform X3

    2. XM_054360499.1 → XP_054216474.1  mitochondrial peptide methionine sulfoxide reductase isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UJ68.1 GenPept UniProtKB/Swiss-Prot:Q9UJ68

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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