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MTRR Gene

protein-coding   GIFtS: 65
GCID: GC05P007851

5-Methyltetrahydrofolate-Homocysteine Methyltransferase...

  See MTRR-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase1 2     Methionine Synthase Reductase2
MSR2 3     Methionine Synthase Reductase, Mitochondrial2
[Methionine Synthase]-Cobalamin Methyltransferase (Cob(II)Alamin Reducing)2     EC 1.16.1.83
cblE2     

External Ids:    HGNC: 74731   Entrez Gene: 45522   Ensembl: ENSG000001242757   OMIM: 6025685   UniProtKB: Q9UBK83   

Export aliases for MTRR gene to outside databases

Previous GC identifers: GC05P008057 GC05P007901 GC05P007921 GC05P007922


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for MTRR Gene:
Methionine is an essential amino acid required for protein synthesis and one-carbon metabolism. Its synthesis is
catalyzed by the enzyme methionine synthase. Methionine synthase eventually becomes inactive due to the oxidation
of its cob(I)alamin cofactor. The protein encoded by this gene regenerates a functional methionine synthase via
reductive methylation. It is a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases.
Patients of the cbl-E complementation group of disorders of folate/cobalamin metabolism are defective in
reductive activation of methionine synthase. Alternative splicing of this gene results in multiple transcript
variants encoding distinct isoforms. (provided by RefSeq, Jul 2008)

GeneCards Summary for MTRR Gene:
MTRR (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) is a protein-coding gene. Diseases associated with MTRR include cble, and homocystinuria-megaloblastic anemia, cbl e type. GO annotations related to this gene include NADP binding and iron ion binding. An important paralog of this gene is NOS3.

UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8
Function: Involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the
maintenance of methionine synthase in a functional state. Necessary for utilization of methylgroups from the
folate cycle, thereby affecting transgenerational epigenetic inheritance. Folate pathway donates methyl groups
necessary for cellular methylation and affects different pathways such as DNA methylation, possibly explaining
the transgenerational epigenetic inheritance effects

Gene Wiki entry for MTRR Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000005.9  NT_006576.17  NC_018916.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the MTRR gene promoter:
         Nkx3-1   TBP   COUP-TF1   COUP   Nkx3-1 v1   HNF-4alpha2   HNF-4alpha1   COUP-TF   POU2F1   POU2F1a   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMTRR promoter sequence
   Search Chromatin IP Primers for MTRR

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MTRR


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5p15.31   Ensembl cytogenetic band:  5p15.31   HGNC cytogenetic band: 5p15.31

MTRR Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MTRR gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05P007851:  view genomic region     (about GC identifiers)

Start:
7,851,299 bp from pter      End:
7,906,138 bp from pter
Size:
54,840 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8 (See protein sequence)
Recommended Name: Methionine synthase reductase  
Size: 725 amino acids; 80410 Da
Cofactor: FAD
Cofactor: FMN
2 PDB 3D structures from and Proteopedia for MTRR:
2QTL (3D)        2QTZ (3D)    
Secondary accessions: O60471 Q32MA9 Q7Z4M8
Alternative splicing: 3 isoforms:  Q9UBK8-1   Q9UBK8-2   Q9UBK8-3   

Explore the universe of human proteins at neXtProt for MTRR: NX_Q9UBK8

Explore proteomics data for MTRR at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See MTRR Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_002445.2  NP_076915.2  

    ENSEMBL proteins: 
     ENSP00000426710   ENSP00000264668   ENSP00000423139   ENSP00000427200   ENSP00000423863  
     ENSP00000424719   ENSP00000424644   ENSP00000402510   ENSP00000426132   ENSP00000424599  
     ENSP00000427416   ENSP00000421318   ENSP00000421991   ENSP00000341918  
    Reactome Protein details: Q9UBK8

    MTRR Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    Novus Biologicals MTRR Protein
    Novus Biologicals MTRR Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for MTRR

     
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    MTRR Antibody Products:

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    LSBio Antibodies in human, mouse, rat for MTRR

    MTRR Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for MTRR
    Cloud-Clone Corp. CLIAs for MTRR
    Search eBioscience for ELISAs for MTRR 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 8):
     IPR017927 Fd_Rdtase_FAD-bd
     IPR001094 Flavdoxin
     IPR008254 Flavodoxin/NO_synth
     IPR001433 OxRdtase_FAD/NAD-bd
     IPR003097 FAD-binding_1

    Graphical View of Domain Structure for InterPro Entry Q9UBK8

    ProtoNet protein and cluster: Q9UBK8

    4 Blocks protein domains:
    IPB001094 Flavodoxin signature
    IPB001433 Oxidoreductase FAD/NAD(P)-binding
    IPB001709 Flavoprotein pyridine nucleotide cytochrome reductase signature
    IPB008254 Flavodoxin/nitric oxide synthase


    UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8
    Similarity: Contains 1 FAD-binding FR-type domain
    Similarity: Contains 1 flavodoxin-like domain


    Find genes that share domains with MTRR           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MTRR_HUMAN, Q9UBK8
    Function: Involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the
    maintenance of methionine synthase in a functional state. Necessary for utilization of methylgroups from the
    folate cycle, thereby affecting transgenerational epigenetic inheritance. Folate pathway donates methyl groups
    necessary for cellular methylation and affects different pathways such as DNA methylation, possibly explaining
    the transgenerational epigenetic inheritance effects
    Catalytic activity: 2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP(+) = 2
    [methionine synthase]-cob(II)alamin + NADPH + 2 S-adenosyl-L-methionine
    Biophysicochemical properties: Kinetic parameters: KM=2.89 uM for NADPH; KM=3540 uM for NADH;

         Genatlas biochemistry entry for MTRR:
    5-methyltetrahydrofolate-homocysteine methyltransferase reductase,77kDa,sulfur aminoacid metabolism,with homology
    to cytochrome p450 reductase and C elegans methionine synthase reductase,activating cobalamin-dependent
    methionine synthase,risk factor for neural tube defect (combined with low cobalamin)

         Enzyme Number (IUBMB): EC 1.16.1.81

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003958NOT NADPH-hemoprotein reductase activity IBA--
    GO:0005506iron ion binding IEA--
    GO:0010181FMN binding TAS9501215
    GO:0016491oxidoreductase activity ----
    GO:0016709oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen IBA--
         
    Find genes that share ontologies with MTRR           About GenesLikeMe


    Phenotypes:
         2 MGI mutant phenotypes (inferred from 1 allele(MGI details for Mtrr):
     growth/size/body  homeostasis/metabolism 

    Find genes that share phenotypes with MTRR           About GenesLikeMe

    Animal Models:
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    miRNA
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    miRTarBase miRNAs that target MTRR:
    hsa-mir-19b-3p (MIRT031186), hsa-let-7b-5p (MIRT001613)

    Block miRNA regulation of human, mouse, rat MTRR using miScript Target Protectors
    2 qRT-PCR Assays for microRNAs that regulate MTRR:
    hsa-miR-374a* hsa-miR-361-5p
    SwitchGear 3'UTR luciferase reporter plasmidMTRR 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 2): MTRR (NM_024010)
    Sino Biological Human cDNA Clone for MTRR
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MTRR

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MTRR


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MTRR_HUMAN, Q9UBK8: Isoform B: Cytoplasm
    MTRR_HUMAN, Q9UBK8: Isoform C: Cytoplasm
    MTRR_HUMAN, Q9UBK8: Isoform A: Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol5
    cytoskeleton4
    nucleus4
    extracellular2
    endoplasmic reticulum1
    golgi apparatus1
    mitochondrion1
    peroxisome1
    plasma membrane1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS9501215
    GO:0045111intermediate filament cytoskeleton IDA--

    Find genes that share ontologies with MTRR           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for MTRR About   (see all 8)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1One carbon pool by folate
    One Carbon Metabolism0.53
    Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics0.34
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics0.35
    Antimetabolite Pathway - Folate Cycle, Pharmacodynamics0.00
    2Defective BTD causes biotidinase deficiency
    Defective BTD causes biotidinase deficiency1.00
    Metabolism of vitamins and cofactors1.00
    Defective AMN causes hereditary megaloblastic anemia 11.00
    Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC1.00
    Defective MMAA causes methylmalonic aciduria type cblA1.00
    Defective MUT causes methylmalonic aciduria mut type1.00
    Defective CD320 causes methylmalonic aciduria1.00
    Defects in cobalamin (B12) metabolism1.00
    3Biological oxidations
    Biological oxidations0.56
    Methylation0.00
    Phase II conjugation0.56
    4Folate Metabolism
    Folate Metabolism0.54
    Vitamin B12 Metabolism0.54
    5Metabolism
    Metabolism0.38


    Find genes that share SuperPaths with MTRR           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    3 BioSystems Pathways for MTRR
        One Carbon Metabolism
    Folate Metabolism
    Vitamin B12 Metabolism


    5 Reactome Pathways for MTRR
        Defective MTR causes methylmalonic aciduria and homocystinuria type cblG
    Sulfur amino acid metabolism
    Cobalamin (Cbl, vitamin B12) transport and metabolism
    Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
    Methylation

    3 PharmGKB Pathways for MTRR
        Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics
    Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for MTRR
    Interactions:

        GeneGlobe Interaction Network for MTRR

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for MTRR (Q9UBK83 ENSP000002646684) via UniProtKB, MINT, STRING, and/or I2D (see all 32)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MMABQ96EY83, ENSP000002668394I2D: score=1 STRING: ENSP00000266839
    PSMC1ENSP000002613034STRING: ENSP00000261303
    UQCRFS1ENSP000003063974STRING: ENSP00000306397
    BIN3ENSP000002764164STRING: ENSP00000276416
    TIMM21ENSP000001695514STRING: ENSP00000169551
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000096sulfur amino acid metabolic process TAS--
    GO:0006306DNA methylation ISS--
    GO:0006555methionine metabolic process TAS9501215
    GO:0006766vitamin metabolic process TAS--
    GO:0006767water-soluble vitamin metabolic process TAS--

    Find genes that share ontologies with MTRR           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for MTRR

    9 HMDB Compounds for MTRR    About this table
    CompoundSynonyms CAS #PubMed Ids
    Cob(I)alaminVitamin B12s (see all 5)18534-66-2--
    Cob(II)alaminVitamin B12r (see all 5)14463-33-3--
    CyanocobalaminDimethylbenzimidazoylcobamide (see all 92)68-19-9--
    FAD1H-Purin-6-amine flavin dinucleotide (see all 21)146-14-5--
    Flavin MononucleotideFMN (see all 19)146-17-8--
    NADPAdenine-nicotinamide dinucleotide phosphate (see all 18)53-59-8--
    NADPH2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)53-57-6--
    S-Adenosylhomocysteine(S)-5'-(S)-(3-Amino-3-carboxypropyl)-5'-thioadenosine (see all 19)979-92-0--
    S-Adenosylmethionine(3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine (see all 16)29908-03-0--

    3 DrugBank Compounds for MTRR    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    CyanocobalaminCyanocob(III)alamin (see all 3)68-19-9targetcofactor17024475 15979034 16268464 15612980 17611986
    L-Methionine(S)-2-amino-4-(methylthio)butanoic acid (see all 6)63-68-3targetproduct of17101561 17079868 17369066
    HydroxocobalaminHydroxomin (see all 2)13422-51-0targetother17139284 17016423

    Selected Novoseek inferred chemical compound relationships for MTRR gene (see all 29)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    methionine 91 469 11466310 (5), 12416982 (5), 12871938 (5), 12482550 (4) (see all 99)
    folate 88.9 79 10484769 (2), 15797993 (2), 14632302 (2), 17220339 (2) (see all 54)
    homocysteine 87.9 98 12482550 (6), 15514263 (3), 12801615 (3), 11472746 (2) (see all 44)
    cob(ii)alamin 85.7 27 19243433 (3), 14717604 (3), 15347655 (3), 17477549 (2) (see all 8)
    cystathionine 85.3 25 17937607 (2), 17553479 (1), 17993766 (1), 14977639 (1) (see all 16)
    cobalamin 82.4 34 10484769 (3), 15347655 (3), 19243433 (2), 17113603 (2) (see all 11)
    vitamin b12 78.4 16 14656028 (2), 12807760 (1), 18226574 (1), 15135249 (1) (see all 13)
    methylmalonic acid 73.9 4 20082058 (1), 17522601 (1)
    5-methyltetrahydrofolate 69.6 6 16047261 (1), 15354395 (1), 17937607 (1)
    methylcobalamin 68.9 4 11006889 (1), 16769880 (1), 12971424 (1)

    3 PharmGKB related drug/compound annotations for MTRR gene    About this table
    Drug/compound PharmGKB Annotation
    vitamin b-complex, plainCA  
    folic acidCA  
    methotrexateCA  



    Find genes that share compounds with MTRR           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for MTRR gene (2 alternative transcripts): 
    NM_002454.2  NM_024010.2  

    Unigene Cluster for MTRR:

    5-methyltetrahydrofolate-homocysteine methyltransferase reductase
    Hs.481551  [show with all ESTs]
    Unigene Representative Sequence: NM_002454
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 26):
    ENST00000507837 ENST00000502509 ENST00000511639 ENST00000513439(uc010itn.1)
    ENST00000264668(uc003jed.3 uc003jee.4 uc003jef.4 uc003jeg.4 uc010ito.3)
    ENST00000508047 ENST00000510279 ENST00000514220 ENST00000511461 ENST00000503550
    ENST00000440940 ENST00000514369 ENST00000502550 ENST00000506877 ENST00000512217
    ENST00000510525 ENST00000508890 ENST00000508101
    miRNA
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    2 qRT-PCR Assays for microRNAs that regulate MTRR:
    hsa-miR-374a* hsa-miR-361-5p
    SwitchGear 3'UTR luciferase reporter plasmidMTRR 3' UTR sequence
    Inhib. RNA
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      QuantiFast Probe-based Assays in human, mouse, rat MTRR

    Additional mRNA sequence: 

    AF025794.1 AF121214.1 AK308442.1 AK311663.1 BC035977.1 BC054816.1 BC062577.1 BC109216.1 
    BC109217.1 

    15 DOTS entries:

    DT.316433  DT.101981916  DT.100764835  DT.75144196  DT.92437944  DT.120815985  DT.100764831  DT.100764837 
    DT.120815957  DT.120815978  DT.120815993  DT.92437947  DT.120816016  DT.92039497  DT.99978919 

    Selected AceView cDNA sequences (see all 165):

    BX093000 AI373715 BC054816 BI772430 AI276625 BC062577 AU124440 AU279788 
    BQ431497 AA279726 AL079567 BM468590 AI016080 BC035977 AA252150 CD559384 
    AA905139 AF025794 AI758177 BV170893 BX375211 CB997527 N94585 AA905280 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for MTRR (see all 14)    About this scheme

    ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b · 6c ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c ^ 10a · 10b ^ 11 ^ 12 ^
    SP1:                    -                                                                             -                 -           -     -           -         
    SP2:                                                                                                  -                 -           -     -           -         
    SP3:                                                                                                  -                 -     -     -     -           -         
    SP4:                                                                                                  -                 -                 -           -         
    SP5:                                                                                                                    -           -     -                     

    ExUns: 13a · 13b · 13c ^ 14 ^ 15 ^ 16 ^ 17a · 17b
    SP1:                                                
    SP2:                                                
    SP3:                                                
    SP4:                                                
    SP5:                                                


    ECgene alternative splicing isoforms for MTRR

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    MTRR expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAGACAGCGG
    MTRR Expression
    About this image


    MTRR expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Brain (Nervous System)    fully expand to see all 2 entries
             Cerebral Cortex
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Ovary (Reproductive System)
             Oviduct
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
    MTRR Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MTRR Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.481551

    UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8
    Tissue specificity: Found in all tissues tested, particularly abundant in skeletal muscle

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for MTRR gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Mtrr1 , 5 5-methyltetrahydrofolate-homocysteine methyltransferase more1, 5 78.88(n)1
    78.74(a)1
      13 (35.54 cM)5
    2100091  NM_172480.21  NP_766068.11 
     685607805 
    chicken
    (Gallus gallus)
    Aves MTRR1 5-methyltetrahydrofolate-homocysteine methyltransferase more 66.52(n)
    61.42(a)
      428502  XM_004935129.1  XP_004935186.1 
    lizard
    (Anolis carolinensis)
    Reptilia MTRR6
    5-methyltetrahydrofolate-homocysteine methyltransf...
    63(a)
    1 ↔ 1
    4(82510544-82538408)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.97232 Xenopus laevis transcribed sequence with weak similarity more 72(n)    BX845943.1 
    zebrafish
    (Danio rerio)
    Actinopterygii mtrr1 5-methyltetrahydrofolate-homocysteine methyltransferase more 58.49(n)
    56.02(a)
      560667  XM_684065.2  XP_689157.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG148823 [methionine synthase]-cobalamin
    methyltransferase more
    31(a)     --
    worm
    (Caenorhabditis elegans)
    Secernentea mtrr-11 mtrr-1 44.58(n)
    34.04(a)
      174471  NM_063577.4  NP_495978.1 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes NCP16
    NADP-cytochrome P450 reductase; involved in ergost...
    25(a)
    1 → many
    VIII(190543-192618) YHR042W


    ENSEMBL Gene Tree for MTRR (if available)
    TreeFam Gene Tree for MTRR (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for MTRR gene
    NOS32  POR2  NOS22  NOS12  

    Find genes that share paralogs with MTRR           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for MTRR
    PGOHUM00000232597


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    MTRR_HUMAN, Q9UBK8: Variant Met-49 has been associated with an increased risk for spina bifida and may be associated
    with chromosomal non-disjunction and Down syndrome


    Selected SNPs for MTRR (see all 974)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0157314
    Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE)4--see VAR_0157312 G R mis40--------
    VAR_0128414
    Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE)4--see VAR_0128412 C R mis40--------
    VAR_0128384
    Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE)4--see VAR_0128382 V M mis40--------
    VAR_0128424
    Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE)4--see VAR_0128422 G R mis40--------
    VAR_0128394
    Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE)4--see VAR_0128392 A T mis40--------
    rs18013941,2,,4
    C,F,Hother17832542(+) GAAATA/GTGTGA 4 I M mis135Minor allele frequency- G:0.41EA MN NS NA WA CSA EU 10160
    rs1446944541,2
    C,F--7828803(+) ACGACA/GTATTT 2 -- us2k11Minor allele frequency- G:0.00NA 4522
    rs768737461,2
    C,F--7828896(+) CTCAGG/ATTGGA 2 -- us2k12Minor allele frequency- A:0.01NA EU 5531
    rs77286211,2
    C,F,H--7828922(+) AAAGTT/CGTTTA 2 -- us2k16Minor allele frequency- C:0.00NS EA NA 4468
    rs1855351911,2
    C--7828970(+) AGTACA/CTGCCT 2 -- us2k10--------

    HapMap Linkage Disequilibrium report for MTRR (7851299 - 7906138 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for MTRR:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2729710CNV Deletion23290073
    esv2663385CNV Deletion23128226
    esv2729709CNV Deletion23290073
    nsv4705CNV Insertion18451855
    nsv508345CNV Loss20534489
    dgv334n21CNV Gain19592680

    Human Gene Mutation Database (HGMD): MTRR
    Locus Specific Mutation Databases (LSDB): MTRR

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing MTRR
    DNA2.0 Custom Variant and Variant Library Synthesis for MTRR

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 602568   
    OMIM disorders: 236270  601634  
    UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8
  • Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE) [MIM:236270]: An autosomal
    recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts
    homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and
    hypomethioninemia. Cells from patients with HMAE fail to incorporate methyltetrahydrofolate into methionine in
    whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent.
    Note=The disease is caused by mutations affecting the gene represented in this entry
  • Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida
    (myelomeningocele) and anencephaly. Note=Disease susceptibility is associated with variations affecting the gene
    represented in this entry

  • 14 diseases for MTRR:    
    About MalaCards
    cble    homocystinuria-megaloblastic anemia, cbl e type    disorders of intracellular cobalamin metabolism    gonorrhea
    cardia cancer    neural tube defects, folate-sensitive    homocysteine plasma level    hyperhomocysteinemia
    homocystinuria    megaloblastic anemia    homocysteinemia    neural tube defects
    spina bifida    coronary artery disease

    4 diseases from the University of Copenhagen DISEASES database for MTRR:
    Hyperhomocysteinemia     Down syndrome     Spina bifida     Homocystinuria

    Find genes that share disorders with MTRR           About GenesLikeMe

    Selected Novoseek inferred disease relationships for MTRR gene (see all 17)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hyperhomocysteinemia 84.3 12 15866085 (1), 10484769 (1), 11006889 (1), 17079868 (1) (see all 7)
    neural tube defects 77.4 9 12812837 (2), 15979034 (2), 18413293 (1), 17101561 (1) (see all 7)
    homocystinuria 73.1 11 12555939 (2), 20120036 (2), 15714522 (1), 9501215 (1) (see all 8)
    anemia megaloblastic 70.4 4 10484769 (1), 17554763 (1)
    spina bifida 60.3 7 12375236 (2), 12812837 (1), 12649067 (1), 10444342 (1) (see all 5)
    down syndrome 59.1 25 11807890 (4), 18257130 (2), 11443546 (2), 16115349 (1) (see all 12)
    gonorrhea 51.7 1 10837198 (1)
    cleft lip 36.5 1 17581676 (1)
    vascular diseases 36.1 1 19348062 (1)
    coronary artery disease 24.2 5 12801615 (2), 11006889 (1), 15612980 (1), 16485733 (1)

    Genatlas disease: MTRR
    megaloblastic anemia,developmental delay,hyperhomocysteinemia and hypomathioninemia,cblE complementation group of
    disorders in folate/cobalamin metabolism

    GeneTests: MTRR
    GeneReviews: MTRR
    Genetic Association Database (GAD): MTRR
    Human Genome Epidemiology (HuGE) Navigator: MTRR (220 documents)

    Export disorders for MTRR gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for MTRR gene, integrated from 10 sources (see all 349):
    (articles sorted by number of sources associating them with MTRR)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. (PubMed id 15979034)1, 2, 4, 7, 9 O'Leary V.B.... Brody L.C. (Mol. Genet. Metab. 2005)
    2. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. (PubMed id 9501215)1, 2, 3, 9 Leclerc D.... Gravel R.A. (Proc. Natl. Acad. Sci. U.S.A. 1998)
    3. The methionine synthase reductase 66A&gt;G polymorphism is a maternal risk factor for spina bifida. (PubMed id 17024475)1, 4, 7, 9 van der Linden I.J....Blom H.J. (J. Mol. Med. 2006)
    4. Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population. (PubMed id 16268464)1, 4, 7, 9 GuAcant-Rodriguez R.M....GueA!nt J.L. (Thromb. Haemost. 2005)
    5. Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. (PubMed id 15612980)1, 4, 7, 9 Miriuka S.G....Cole D.E. (Transpl. Int. 2005)
    6. Restricted role for methionine synthase reductase defined by subcellular localization. (PubMed id 18221906)1, 2, 9 Froese D.S....Gravel R.A. (Mol. Genet. Metab. 2008)
    7. Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry. (PubMed id 17892308)1, 2, 9 Wolthers K.R.... Scrutton N.S. (Biochemistry 2007)
    8. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms as risk factors for hepatocellular carcinoma in a Korean population. (PubMed id 19035314)1, 4, 9 Kwak S.Y....Hwang S.G. (Anticancer Res. 2008)
    9. Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption. (PubMed id 17376725)1, 4, 9 Ananth C.V....Rozen R.R. (Mol. Genet. Metab. 2007)
    10. Effects of polymorphisms of methionine synthase and methionine synthase reductase on total plasma homocysteine in the NHLBI Family Heart Study. (PubMed id 12482550)1, 4, 9 Jacques P.F....Rozen R. (Atherosclerosis 2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4552 HGNC: 7473 AceView: MTRR Ensembl:ENSG00000124275 euGenes: HUgn4552
    ECgene: MTRR H-InvDB: MTRR

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for MTRR Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=MTRR[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for MTRR gene:
    Search GeneIP for patents involving MTRR

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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