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

Summary

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

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_000072.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

M63445 (e-PCR)
- UniSTS:159524

PMC133862P1 (e-PCR)
- UniSTS:270671

Mthfd2 (e-PCR), detects polymorphism
- UniSTS:507073

AW558851 (e-PCR)
- UniSTS:179403

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 more info	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

EC 1.5.1.15

EC 3.5.4.9

XP_006505760.1

EC 1.5.1.15

EC 3.5.4.9

XP_011239547.1

EC 1.5.1.15

EC 3.5.4.9

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)

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

NC_000072.7 Reference GRCm39 C57BL/6J

Range

83282686..83302926 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]