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    Mthfd2 methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase [ Mus musculus (house mouse) ]

    Gene ID: 17768, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Mthfd2provided by MGI
    Official Full Name
    methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolaseprovided by MGI
    Primary source
    MGI:MGI:1338850
    See related
    Ensembl:ENSMUSG00000005667 AllianceGenome:MGI:1338850
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    NMDMC
    Summary
    Predicted to enable several functions, including magnesium ion binding activity; methenyltetrahydrofolate cyclohydrolase activity; and methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity. Predicted to be involved in tetrahydrofolate interconversion. Predicted to act upstream of or within one-carbon metabolic process. Located in mitochondrion. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; respiratory system; and sensory organ. Orthologous to human MTHFD2 (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Broad expression in liver E14 (RPKM 25.7), liver E14.5 (RPKM 21.2) and 17 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    6 C3; 6 35.94 cM
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 6 NC_000072.7 (83282686..83302926, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 6 NC_000072.6 (83305704..83326011, complement)

    Chromosome 6 - NC_000072.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E6447 Neighboring gene STARR-seq mESC enhancer starr_16458 Neighboring gene predicted gene 15624 Neighboring gene dynactin 1 Neighboring gene solute carrier family 4, sodium bicarbonate cotransporter, member 5 Neighboring gene STARR-seq mESC enhancer starr_16459 Neighboring gene STARR-positive B cell enhancer ABC_E4836 Neighboring gene STARR-positive B cell enhancer ABC_E1323 Neighboring gene STARR-positive B cell enhancer ABC_E6448 Neighboring gene STARR-seq mESC enhancer starr_16463 Neighboring gene MOB kinase activator 1A Neighboring gene bolA family member 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells. Yue L, et al. Stem Cell Reports, 2020 Aug 11. PMID 32679066, Free PMC Article
    2. Mammalian fibroblasts lacking mitochondrial NAD+-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase are glycine auxotrophs. Patel H, et al. J Biol Chem, 2003 May 23. PMID 12646567
    3. Mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is essential for embryonic development. Di Pietro E, et al. Mol Cell Biol, 2002 Jun. PMID 12024029, Free PMC Article
    4. Isolation and characterization of cDNA clones encoding the murine NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase. Bélanger C, et al. J Biol Chem, 1989 Mar 25. PMID 2647744
    5. Structural organization of the murine gene encoding NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase. Bélanger C, et al. Gene, 1991 Jan 15. PMID 1999293

    See all (43) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF-kappaB Activation and Protects against Inflammatory Responses.
      Title: Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF-κB Activation and Protects against Inflammatory Responses.
    2. Mitochondrial one-carbon metabolic enzyme MTHFD2 facilitates mammary gland development during pregnancy.
      Title: Mitochondrial one-carbon metabolic enzyme MTHFD2 facilitates mammary gland development during pregnancy.
    3. MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function.
      Title: MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function.
    4. Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells.
      Title: Mthfd2 Modulates Mitochondrial Function and DNA Repair to Maintain the Pluripotency of Mouse Stem Cells.
    5. Data suggest that Ad4BP plays role in regulation of intracellular NADPH concentration via transcription of Me1 and Mthfd2 genes in adrenocortical cells. (Ad4BP = nuclear receptor subfamily 5 group A member 1; Me1 = malic enzyme 1; Mthfd2 = bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase)
      Title: Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells.
    6. A mutation in methylenetetrahydrofolate reductase (MTHFR) gene, may contribute to the risk of both arterial and deep-vein thrombosis in patients with nephrotic syndrome.
      Title: Arterial thrombosis associated with factor V Leiden and methylenetetrahydrofolate reductase C677T mutation in childhood membranous glomerulonephritis.
    7. Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase derived from a trifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase.
      Title: Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase derived from a trifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase.
    8. results demonstrate a metabolic role for NAD+ dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase in supporting purine biosynthesis
      Title: Mammalian fibroblasts lacking mitochondrial NAD+-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase are glycine auxotrophs.
    9. Results describe the ubiquitous expression of NAD-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase in mouse embryos, suggesting it has a broad role during embryogenesis.
      Title: The expression of mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase supports a role in rapid cell growth.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Targeted (4)  1 citation
    • Endonuclease-mediated (2) 

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables catalytic activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables magnesium ion binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables methenyltetrahydrofolate cyclohydrolase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables methenyltetrahydrofolate cyclohydrolase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables methenyltetrahydrofolate cyclohydrolase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables methylenetetrahydrofolate dehydrogenase (NAD+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables methylenetetrahydrofolate dehydrogenase (NAD+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables methylenetetrahydrofolate dehydrogenase (NAD+) activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables methylenetetrahydrofolate dehydrogenase (NADP+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables methylenetetrahydrofolate dehydrogenase (NADP+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables methylenetetrahydrofolate dehydrogenase (NADP+) activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables oxidoreductase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phosphate ion binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    acts_upstream_of_or_within metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within one-carbon metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tetrahydrofolate interconversion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tetrahydrofolate metabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrion HDA PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
    NP_032664.1
    XP_006505760.1
    XP_011239547.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

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

    mRNA and Protein(s)

    1. NM_008638.2 → NP_032664.1  bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial precursor

      See identical proteins and their annotated locations for NP_032664.1

      Status: VALIDATED

      Source sequence(s)
      AK159680, BY068806, DV651355
      Consensus CDS
      CCDS20277.1
      UniProtKB/Swiss-Prot
      P18155, Q3TMN4
      UniProtKB/TrEMBL
      Q3U8E7
      Related
      ENSMUSP00000005810.7, ENSMUST00000005810.9
      Conserved Domains (1) summary
      COG0190
      Location:39 → 333
      FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000072.7 Reference GRCm39 C57BL/6J

      Range
      83282686..83302926 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006505697.5 → XP_006505760.1  bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial isoform X2

      UniProtKB/TrEMBL
      Q3U8E7
      Conserved Domains (1) summary
      COG0190
      Location:20 → 314
      FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]

    2. XM_011241245.4 → XP_011239547.1  bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q3U8E7
      Conserved Domains (1) summary
      COG0190
      Location:42 → 336
      FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P18155.1 GenPept UniProtKB/Swiss-Prot:P18155

    Gene LinkOut

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

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