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

    Gene ID: 4552, updated on 15-Sep-2018

    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; Vega:OTTHUMG00000090477
    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

    Genomic context

    See MTRR in Genome Data Viewer
    Location:
    5p15.31
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (7851186..7901124)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (7851299..7901237)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107986403 Neighboring gene long intergenic non-protein coding RNA 2142 Neighboring gene uncharacterized LOC105374646 Neighboring gene adenylate cyclase 2 Neighboring gene chromosome 5 open reading frame 49 Neighboring gene FAST kinase domains 3 Neighboring gene semaphorin 5A pseudogene Neighboring gene RNA, U1 small nuclear 76, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • 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 Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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 BioSystems

    • Biological oxidations, organism-specific biosystem (from REACTOME)
      Biological oxidations, organism-specific biosystemAll organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ...
    • Cobalamin (Cbl, vitamin B12) transport and metabolism, organism-specific biosystem (from REACTOME)
      Cobalamin (Cbl, vitamin B12) transport and metabolism, organism-specific biosystemVitamin B12 (cobalamin, Cbl) is a water-soluble vitamin with a key role in blood formation and normal functioning of the brain and nervous system. Cbl consists of a planar corrin ring coordinating wi...
    • Defective MTR causes methylmalonic aciduria and homocystinuria type cblG, organism-specific biosystem (from REACTOME)
      Defective MTR causes methylmalonic aciduria and homocystinuria type cblG, organism-specific biosystemDefects in MTR cause methylcobalamin deficiency type G (cblG; MIM:250940), an autosomal recessive inherited disease that causes mental retardation, macrocytic anemia, and homocystinuria (Leclerc et a...
    • Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE, organism-specific biosystem (from REACTOME)
      Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE, organism-specific biosystemDefects in MTRR cause methylcobalamin deficiency type E (cblE; methionine synthase reductase deficiency; MIM:236270) (Wilson et al. 1999). Patients with cblE exhibit megaloblastic anemia and hyperhom...
    • Defects in cobalamin (B12) metabolism, organism-specific biosystem (from REACTOME)
      Defects in cobalamin (B12) metabolism, organism-specific biosystemCobalamin (Cbl, vitamin B12) is a nutrient essential for normal functioning of the brain and nervous system and for the formation of blood. Cbl-dependent methionine synthase (MTR) is required for con...
    • Defects in vitamin and cofactor metabolism, organism-specific biosystem (from REACTOME)
      Defects in vitamin and cofactor metabolism, organism-specific biosystemVitamins are essential nutrients, required in small amounts from the diet for the normal growth and development of a multicellular organism. Where there is vitamin deficiency, either by poor diet or ...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diseases of metabolism, organism-specific biosystem (from REACTOME)
      Diseases of metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Folate Metabolism, organism-specific biosystem (from WikiPathways)
      Folate Metabolism, organism-specific biosystem
      Folate Metabolism
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of amino acids and derivatives, organism-specific biosystem (from REACTOME)
      Metabolism of amino acids and derivatives, organism-specific biosystemThis group of reactions is responsible for: 1) the breakdown of amino acids; 2) the synthesis of urea from ammonia and amino groups generated by amino acid breakdown; 3) the synthesis of the ten amin...
    • Metabolism of vitamins and cofactors, organism-specific biosystem (from REACTOME)
      Metabolism of vitamins and cofactors, organism-specific biosystemVitamins are a diverse group of organic compounds, classified according to their solubility, either fat-soluble or water-soluble, that are either not synthesized or synthesized only in limited amount...
    • Metabolism of water-soluble vitamins and cofactors, organism-specific biosystem (from REACTOME)
      Metabolism of water-soluble vitamins and cofactors, organism-specific biosystemVitamins are a diverse group of organic compounds, required in small amounts in the diet. They have distinct biochemical roles, often as coenzymes, and are either not synthesized or synthesized only ...
    • Methylation, organism-specific biosystem (from REACTOME)
      Methylation, organism-specific biosystemMethylation is a common but minor pathway of Phase II conjugation compared to glucuronidation or sulfonation. The cofactor used in methylation conjugation is S-adenosylmethionine (SAM). SAM is the ...
    • One Carbon Metabolism, organism-specific biosystem (from WikiPathways)
      One Carbon Metabolism, organism-specific biosystemThis one-carbon metabolism pathway is centered around folate. Folate has two key carbon-carbon double bonds. Saturating one of them yields dihydrofolate (DHF) and adding an additional molecule of hyd...
    • Phase II conjugation, organism-specific biosystem (from REACTOME)
      Phase II conjugation, organism-specific biosystemPhase II of biotransformation is concerned with conjugation, that is using groups from cofactors to react with functional groups present or introduced from phase I on the compound. The enzymes involv...
    • Sulfur amino acid metabolism, organism-specific biosystem (from REACTOME)
      Sulfur amino acid metabolism, organism-specific biosystemThe main sulfur amino acids are methionine, cysteine, homocysteine and taurine. Of these, the first two are proteinogenic.This group of reactions contains all processes that 1) break down sulfur amin...
    • Vitamin B12 Metabolism, organism-specific biosystem (from WikiPathways)
      Vitamin B12 Metabolism, organism-specific biosystem
      Vitamin B12 Metabolism

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • MGC129643

    Gene Ontology Provided by GOA

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

    General protein information

    Preferred Names
    methionine synthase reductase
    Names
    [methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing)
    methionine synthase reductase, mitochondrial
    NP_002445.2
    XP_024301831.1
    XP_024301832.1
    XP_024301833.1

    NCBI Reference Sequences (RefSeq)

    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_008856.1 RefSeqGene

      Range
      5001..37021
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001364440.1NP_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
      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_001364441.1NP_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
      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_001364442.1NP_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
      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_002454.2NP_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
      Q9UBK8
      Related
      ENSP00000402510.2, OTTHUMP00000220821, ENST00000440940.6, OTTHUMT00000366333
      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_024010.3NP_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
      CCDS3874.1
      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_134480.1 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_134481.1 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_134482.1 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
      Related
      ENST00000511461.5, OTTHUMT00000366327
    4. NR_157168.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    5. NR_157169.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    6. NR_157170.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    7. NR_157171.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    8. NR_157172.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    9. NR_157173.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    10. NR_157174.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    11. NR_157175.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    12. NR_157176.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    13. NR_157177.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174
    14. NR_157178.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC010346, AC025174

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

      Range
      7851186..7901124
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024446064.1XP_024301832.1  methionine synthase reductase isoform X2

      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. XM_024446065.1XP_024301833.1  methionine synthase reductase isoform X2

      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_024446063.1XP_024301831.1  methionine synthase reductase isoform X1

      Conserved Domains (2) summary
      cd06203
      Location:292712
      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:21157
      Flavodoxin_1

    RNA

    1. XR_001742077.1 RNA Sequence

    2. XR_001742076.1 RNA Sequence

    3. XR_001742071.1 RNA Sequence

    4. XR_925614.1 RNA Sequence

    5. XR_001742072.1 RNA Sequence

    6. XR_001742075.1 RNA Sequence

    7. XR_001742074.1 RNA Sequence

      Related
      ENST00000510525.5, OTTHUMT00000366328
    8. XR_001742070.2 RNA Sequence

    9. XR_001742073.2 RNA Sequence

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