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    MTRR 5-methyltetrahydrofolate-homocysteine methyltransferase reductase [ Homo sapiens (human) ]

    Gene ID: 4552, updated on 10-Dec-2024

    Summary

    Official Symbol
    MTRRprovided by HGNC
    Official Full Name
    5-methyltetrahydrofolate-homocysteine methyltransferase reductaseprovided by HGNC
    Primary source
    HGNC:HGNC:7473
    See related
    Ensembl:ENSG00000124275 MIM:602568; AllianceGenome:HGNC:7473
    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
    MSR; cblE
    Summary
    This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]
    Expression
    Ubiquitous expression in lung (RPKM 14.2), kidney (RPKM 10.4) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See MTRR in Genome Data Viewer
    Location:
    5p15.31
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (7850859..7901113)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (7789841..7840236)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (7869261..7901226)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107986403 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7394801-7395566 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7395567-7396332 Neighboring gene long intergenic non-protein coding RNA 2142 Neighboring gene uncharacterized LOC105374646 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7420020-7420743 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7420744-7421468 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr5:7422307-7423176 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7424665-7425194 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7425195-7425722 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr5:7427184-7427875 Neighboring gene adenylate cyclase 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:7480982-7481482 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:7481483-7481983 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:7515349-7515849 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:7526205-7526704 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7596934-7597448 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7597449-7597963 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:7663263-7663836 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr5:7663837-7664409 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:7667125-7668324 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:7683613-7683799 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22344 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22345 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22346 Neighboring gene Sharpr-MPRA regulatory region 1766 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7815313-7815850 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7816816-7817543 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:7816087-7816815 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15904 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15905 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15906 Neighboring gene cilia and flagella associated protein 90 Neighboring gene FAST kinase domains 3 Neighboring gene uncharacterized LOC124900936 Neighboring gene semaphorin 5A pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Methylcobalamin deficiency type cblE Compare labs
    Neural tube defects, folate-sensitive
    MedGen: C1866558 OMIM: 601634 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    Identification of novel germline polymorphisms governing capecitabine sensitivity.
    EBI GWAS Catalog

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC129643

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables FAD binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables FMN binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables FMN binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables NADPH binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables NADPH-hemoprotein reductase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables [methionine synthase] reductase (NADPH) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables [methionine synthase] reductase (NADPH) activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables [methionine synthase] reductase (NADPH) activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables flavin adenine dinucleotide binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables flavin adenine dinucleotide binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in S-adenosylmethionine cycle ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in cobalamin metabolic process TAS
    Traceable Author Statement
    more info
     
    involved_in folic acid metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in folic acid metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in homocysteine catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in homocysteine metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in methionine biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in methionine biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of cystathionine beta-synthase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in intermediate filament cytoskeleton IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     

    General protein information

    Preferred Names
    methionine synthase reductase
    Names
    [methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing)
    aqCbl reductase
    aquacobalamin reductase
    methionine synthase reductase, mitochondrial
    NP_001351369.1
    NP_001351370.1
    NP_001351371.1
    NP_002445.2
    NP_076915.3
    XP_024301832.1
    XP_047273189.1
    XP_047273190.1
    XP_047273191.1
    XP_047273192.1
    XP_047273193.1
    XP_047273194.1
    XP_054208631.1
    XP_054208632.1
    XP_054208633.1
    XP_054208634.1
    XP_054208635.1
    XP_054208636.1
    XP_054208637.1

    NCBI Reference Sequences (RefSeq)

    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_008856.2 RefSeqGene

      Range
      23291..55256
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001364440.2NP_001351369.1  methionine synthase reductase

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) represents the longest transcript. Variants 1, 2, 6, 7, and 8 all encode the same protein.
      Source sequence(s)
      AC010346, AC025174
      Consensus CDS
      CCDS47190.1
      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
      Conserved Domains (2) summary
      cd06203
      Location:277697
      methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
      pfam00258
      Location:6142
      Flavodoxin_1; Flavodoxin
    2. NM_001364441.2NP_001351370.1  methionine synthase reductase

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
      Source sequence(s)
      AC010346, AC025174
      Consensus CDS
      CCDS47190.1
      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
      Conserved Domains (2) summary
      cd06203
      Location:277697
      methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
      pfam00258
      Location:6142
      Flavodoxin_1; Flavodoxin
    3. NM_001364442.2NP_001351371.1  methionine synthase reductase

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
      Source sequence(s)
      AC010346, AC025174
      Consensus CDS
      CCDS47190.1
      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
      Conserved Domains (2) summary
      cd06203
      Location:277697
      methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
      pfam00258
      Location:6142
      Flavodoxin_1; Flavodoxin
    4. NM_002454.3NP_002445.2  methionine synthase reductase

      See identical proteins and their annotated locations for NP_002445.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
      Source sequence(s)
      BC054816, BC109216
      Consensus CDS
      CCDS47190.1
      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
      Related
      ENSP00000402510.2, ENST00000440940.7
      Conserved Domains (2) summary
      cd06203
      Location:277697
      methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
      pfam00258
      Location:6142
      Flavodoxin_1; Flavodoxin
    5. NM_024010.4NP_076915.3  methionine synthase reductase

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.
      Source sequence(s)
      AC010346, AC025174
      Consensus CDS
      CCDS47190.1
      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
      Related
      ENSP00000264668.2, ENST00000264668.6
      Conserved Domains (2) summary
      cd06203
      Location:277697
      methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
      pfam00258
      Location:6142
      Flavodoxin_1; Flavodoxin

    RNA

    1. NR_134480.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC054816, BC109217, DA384356
    2. NR_134481.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AF121214, BC035977, BC054816
    3. NR_134482.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC054816, BC062577, BC109217
    4. NR_157168.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    5. NR_157169.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
      Related
      ENST00000511461.5
    6. NR_157170.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    7. NR_157171.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    8. NR_157172.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    9. NR_157173.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    10. NR_157174.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    11. NR_157175.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    12. NR_157176.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    13. NR_157177.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    14. NR_157178.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      7850859..7901113
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047417233.1XP_047273189.1  methionine synthase reductase isoform X1

      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
    2. XM_024446064.2XP_024301832.1  methionine synthase reductase isoform X1

      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
      Conserved Domains (2) summary
      cd06203
      Location:277697
      methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...
      pfam00258
      Location:6142
      Flavodoxin_1; Flavodoxin
    3. XM_047417234.1XP_047273190.1  methionine synthase reductase isoform X1

      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
    4. XM_047417235.1XP_047273191.1  methionine synthase reductase isoform X2

    5. XM_047417236.1XP_047273192.1  methionine synthase reductase isoform X3

    6. XM_047417237.1XP_047273193.1  methionine synthase reductase isoform X4

      UniProtKB/TrEMBL
      H0Y8S9
      Related
      ENSP00000421991.1, ENST00000510525.5
    7. XM_047417238.1XP_047273194.1  methionine synthase reductase isoform X5

      UniProtKB/TrEMBL
      H0Y8S9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      7789841..7840236
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352656.1XP_054208631.1  methionine synthase reductase isoform X1

      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
    2. XM_054352658.1XP_054208633.1  methionine synthase reductase isoform X1

      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
    3. XM_054352657.1XP_054208632.1  methionine synthase reductase isoform X1

      UniProtKB/Swiss-Prot
      O60471, Q32MA9, Q7Z4M8, Q9UBK8
    4. XM_054352659.1XP_054208634.1  methionine synthase reductase isoform X2

    5. XM_054352660.1XP_054208635.1  methionine synthase reductase isoform X3

    6. XM_054352661.1XP_054208636.1  methionine synthase reductase isoform X4

      UniProtKB/TrEMBL
      H0Y8S9
    7. XM_054352662.1XP_054208637.1  methionine synthase reductase isoform X5

      UniProtKB/TrEMBL
      H0Y8S9