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

Gene ID: 17768, updated on 2-Nov-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
Enables methenyltetrahydrofolate cyclohydrolase activity; methylenetetrahydrofolate dehydrogenase (NAD+) activity; and methylenetetrahydrofolate dehydrogenase (NADP+) activity. Predicted to be involved in tetrahydrofolate interconversion. 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, Nov 2024]
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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See Mthfd2 in Genome Data Viewer
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 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. Analysis of the promoter region of the gene encoding NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase. Bélanger C, et al. Nucleic Acids Res, 1991 Aug 25. PMID 1843253, Free PMC Article
  2. Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF-κB Activation and Protects against Inflammatory Responses. Cui Y, et al. J Immunol, 2024 Apr 15. PMID 38407485
  3. Mammalian fibroblasts lacking mitochondrial NAD+-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase are glycine auxotrophs. Patel H, et al. J Biol Chem, 2003 May 23. PMID 12646567
  4. 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
  5. 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

See all (49) 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)
  • Endonuclease-mediated (2) 
  • Targeted (4)  1 citation

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 magnesium ion binding ISO
Inferred from Sequence Orthology
more info
  
enables magnesium ion binding ISS
Inferred from Sequence or Structural Similarity
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 (NAD+) activity ISS
Inferred from Sequence or Structural Similarity
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 (NADP+) activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables phosphate ion binding ISO
Inferred from Sequence Orthology
more info
  
enables phosphate ion binding ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in 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 IEA
Inferred from Electronic Annotation
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

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