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MSRB3 methionine sulfoxide reductase B3 [ Homo sapiens (human) ]

Gene ID: 253827, updated on 7-Apr-2024

Summary

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Official Symbol
MSRB3provided by HGNC
Official Full Name
methionine sulfoxide reductase B3provided by HGNC
Primary source
HGNC:HGNC:27375
See related
Ensembl:ENSG00000174099 MIM:613719; AllianceGenome:HGNC:27375
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
DFNB74
Summary
The protein encoded by this gene catalyzes the reduction of methionine sulfoxide to methionine. This enzyme acts as a monomer and requires zinc as a cofactor. Several transcript variants encoding two different isoforms have been found for this gene. One of the isoforms localizes to mitochondria while the other localizes to endoplasmic reticula. [provided by RefSeq, Jul 2010]
Expression
Broad expression in endometrium (RPKM 66.2), esophagus (RPKM 57.7) and 22 other tissues See more
Orthologs
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Genomic context

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Location:
12q14.3
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (65278683..65466907)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (65257707..65446355)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (65672463..65860687)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902953 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6606 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:65563126-65563698 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4630 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:65564244-65564447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6608 Neighboring gene Sharpr-MPRA regulatory region 14888 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4631 Neighboring gene LEM domain containing 3 Neighboring gene MPRA-validated peak1765 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:65655701-65656202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:65656203-65656702 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4632 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4633 Neighboring gene uncharacterized LOC124902954 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:65824313-65825512 Neighboring gene keratin 18 pseudogene 60 Neighboring gene uncharacterized LOC105369809 Neighboring gene MSRB3 antisense RNA 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:65930061-65931260 Neighboring gene uncharacterized LOC105369187 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:65950046-65951245 Neighboring gene uncharacterized LOC105369808

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
  • 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. MSRB3 promotes the progression of clear cell renal cell carcinoma via regulating endoplasmic reticulum stress. Ye X, et al. Pathol Res Pract, 2020 Feb. PMID 31889586
  2. Methionine Sulfoxide Reductase-B3 Risk Allele Implicated in Alzheimer's Disease Associates with Increased Odds for Brain Infarcts. Conner SC, et al. J Alzheimers Dis, 2019. PMID 30775993, Free PMC Article
  3. Methionine sulfoxide reductase B3 requires resolving cysteine residues for full activity and can act as a stereospecific methionine oxidase. Cao Z, et al. Biochem J, 2018 Feb 28. PMID 29420254, Free PMC Article
  4. Methionine Sulfoxide Reductase-B3 (MsrB3) Protein Associates with Synaptic Vesicles and its Expression Changes in the Hippocampi of Alzheimer's Disease Patients. Adams SL, et al. J Alzheimers Dis, 2017. PMID 28777754, Free PMC Article
  5. Down-regulation of MsrB3 induces cancer cell apoptosis through reactive oxygen species production and intrinsic mitochondrial pathway activation. Kwak GH, et al. Biochem Biophys Res Commun, 2017 Jan 29. PMID 28007593

See all (45) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MicroRNA-874-3p Aggravates Doxorubicin-Induced Renal Podocyte Injury via Targeting Methionine Sulfoxide Reductase B3.
    Title: MicroRNA-874-3p Aggravates Doxorubicin-Induced Renal Podocyte Injury via Targeting Methionine Sulfoxide Reductase B3.
  2. MSRB3 promotes the progression of clear cell renal cell carcinoma via regulating endoplasmic reticulum stress.
    Title: MSRB3 promotes the progression of clear cell renal cell carcinoma via regulating endoplasmic reticulum stress.
  3. individuals with MSRB3 rs61921502 minor allele had increased odds for brain infarcts on MRI compared to those with no minor allele
    Title: Methionine Sulfoxide Reductase-B3 Risk Allele Implicated in Alzheimer's Disease Associates with Increased Odds for Brain Infarcts.
  4. we characterise the mammalian enzyme Msr B3. There are two splice variants of this enzyme that differ only in their N-terminal signal sequence, which directs the protein to either the endoplasmic reticulum (ER) or mitochondria
    Title: Methionine sulfoxide reductase B3 requires resolving cysteine residues for full activity and can act as a stereospecific methionine oxidase.
  5. This characterization of GWAS-implicated MSRB3 protein expression in human hippocampus suggests that patterns of neuronal and vascular MsrB3 protein expression reflect or underlie pathology associated with Alzheimer disease.
    Title: Methionine Sulfoxide Reductase-B3 (MsrB3) Protein Associates with Synaptic Vesicles and its Expression Changes in the Hippocampi of Alzheimer's Disease Patients.
  6. Oncogene induction in differentiated cells induces massive DNA damage, mammary stem cells are resistant, owing to a preemptive program driven by ZEB1 and MSRB3. The prevention of oncogene-induced DNA damage precludes induction of the oncosuppressive p53-dependent DNA-damage response, thereby increasing stem cells' intrinsic susceptibility to malignant transformation.
    Title: A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
  7. The data suggest that MsrB3 attenuates HO-1 induction by inhibiting reactive oxygen species production, endoplasmic reticulum stress, and Nrf2 activation.
    Title: Methionine sulfoxide reductase B3 deficiency stimulates heme oxygenase-1 expression via ROS-dependent and Nrf2 activation pathways.
  8. MsrB3 plays an important role in cancer cell survival through the modulation of the intrinsic apoptosis pathway.
    Title: Down-regulation of MsrB3 induces cancer cell apoptosis through reactive oxygen species production and intrinsic mitochondrial pathway activation.
  9. Taken together, our results suggest that MsrB3 plays a critical role in cancer cell apoptosis through the modulation of ER stress status.
    Title: MsrB3 deficiency induces cancer cell apoptosis through p53-independent and ER stress-dependent pathways.
  10. MsrB3 deficiency activates the cell cycle inhibitors p21 and p27.
    Title: Methionine sulfoxide reductase B3 deficiency inhibits cell growth through the activation of p53-p21 and p27 pathways.
Submit: New GeneRIF Correction See all GeneRIFs (16)

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

Associated conditions

Description Tests
Autosomal recessive nonsyndromic hearing loss 74
MedGen: C2239351 OMIM: 613718 GeneReviews: Not available
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EBI GWAS Catalog

Description
A genome-wide association study for diabetic nephropathy genes in African Americans.
EBI GWAS Catalog
A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales.
EBI GWAS Catalog
Common variants at 12q14 and 12q24 are associated with hippocampal volume.
EBI GWAS Catalog
Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances.
EBI GWAS Catalog
Genome-wide association study reveals multiple loci associated with primary tooth development during infancy.
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

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

Clone Names

  • FLJ36866, DKFZp686C1178

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables L-methionine-(R)-S-oxide reductase activity IEA
Inferred from Electronic Annotation
more info
  
enables peptide-methionine (R)-S-oxide reductase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables peptide-methionine (R)-S-oxide reductase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables peptide-methionine (R)-S-oxide reductase activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables zinc ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in protein repair IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein repair TAS
Traceable Author Statement
more info
  
involved_in response to oxidative stress IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
methionine-R-sulfoxide reductase B3
Names
methionine-R-sulfoxide reductase B3, mitochondrial
NP_001026849.1
NP_001180389.1
NP_001180390.1
NP_932346.1
XP_024304686.1
XP_024304687.1
XP_024304688.1
XP_024304689.1
XP_054227626.1
XP_054227627.1
XP_054227628.1
XP_054227629.1

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.

Genomic

  1. NG_023441.1 RefSeqGene

    Range
    5041..193265
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001031679.3 → NP_001026849.1  methionine-R-sulfoxide reductase B3 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001026849.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1. Variants 2, 3, and 4 all encode isoform 2.
    Source sequence(s)
    AC025419, AK293084, AY358229, BX648776
    Consensus CDS
    CCDS31853.1
    UniProtKB/TrEMBL
    F5H199
    Related
    ENSP00000312274.6, ENST00000308259.10
    Conserved Domains (1) summary
    PRK00222
    Location:35 → 163
    PRK00222; methionine sulfoxide reductase B; Provisional

  2. NM_001193460.2 → NP_001180389.1  methionine-R-sulfoxide reductase B3 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001180389.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1. Variants 2, 3, and 4 all encode isoform 2.
    Source sequence(s)
    AC025419, AY358229, BC040053, BX648776, DC357690
    Consensus CDS
    CCDS31853.1
    UniProtKB/TrEMBL
    F5H199
    Related
    ENSP00000441650.1, ENST00000535664.5
    Conserved Domains (1) summary
    PRK00222
    Location:35 → 163
    PRK00222; methionine sulfoxide reductase B; Provisional

  3. NM_001193461.2 → NP_001180390.1  methionine-R-sulfoxide reductase B3 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001180390.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1. Variants 2, 3, and 4 all encode isoform 2.
    Source sequence(s)
    AC025419, AC026124, AY358229, BX500552, BX648776
    Consensus CDS
    CCDS31853.1
    UniProtKB/TrEMBL
    F5H199
    Related
    ENSP00000481483.1, ENST00000614640.4
    Conserved Domains (1) summary
    PRK00222
    Location:35 → 163
    PRK00222; methionine sulfoxide reductase B; Provisional

  4. NM_198080.4 → NP_932346.1  methionine-R-sulfoxide reductase B3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_932346.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AC025419, AY358229, BX648776, DC357690
    Consensus CDS
    CCDS8973.1
    UniProtKB/Swiss-Prot
    B4DR19, B7ZAQ0, Q6UXS2, Q8IXL7
    Related
    ENSP00000347324.3, ENST00000355192.8
    Conserved Domains (1) summary
    PRK00222
    Location:42 → 170
    PRK00222; methionine sulfoxide reductase B; Provisional

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    65278683..65466907
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024448921.2 → XP_024304689.1  methionine-R-sulfoxide reductase B3 isoform X1

    UniProtKB/TrEMBL
    F5H199
    Related
    ENSP00000494941.1, ENST00000646299.1
    Conserved Domains (1) summary
    PRK00222
    Location:35 → 163
    PRK00222; methionine sulfoxide reductase B; Provisional

  2. XM_024448919.2 → XP_024304687.1  methionine-R-sulfoxide reductase B3 isoform X1

    UniProtKB/TrEMBL
    F5H199
    Related
    ENSP00000494265.1, ENST00000642411.1
    Conserved Domains (1) summary
    PRK00222
    Location:35 → 163
    PRK00222; methionine sulfoxide reductase B; Provisional

  3. XM_024448918.2 → XP_024304686.1  methionine-R-sulfoxide reductase B3 isoform X1

    UniProtKB/TrEMBL
    F5H199
    Related
    ENSP00000496008.1, ENST00000642404.1
    Conserved Domains (1) summary
    PRK00222
    Location:35 → 163
    PRK00222; methionine sulfoxide reductase B; Provisional

  4. XM_024448920.1 → XP_024304688.1  methionine-R-sulfoxide reductase B3 isoform X1

    UniProtKB/TrEMBL
    F5H199
    Conserved Domains (1) summary
    PRK00222
    Location:35 → 163
    PRK00222; methionine sulfoxide reductase B; Provisional

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    65257707..65446355
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054371653.1 → XP_054227628.1  methionine-R-sulfoxide reductase B3 isoform X1

  2. XM_054371651.1 → XP_054227626.1  methionine-R-sulfoxide reductase B3 isoform X1

  3. XM_054371652.1 → XP_054227627.1  methionine-R-sulfoxide reductase B3 isoform X1

  4. XM_054371654.1 → XP_054227629.1  methionine-R-sulfoxide reductase B3 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IXL7.2 GenPept UniProtKB/Swiss-Prot:Q8IXL7

Gene LinkOut

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