Dhfr dihydrofolate reductase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Dhfrprovided by MGI
Official Full Name: dihydrofolate reductaseprovided by MGI
Primary source: MGI:MGI:94890
See related: Ensembl:ENSMUSG00000021707 AllianceGenome:MGI:94890
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: 8430436I03Rik
Summary: Enables dihydrofolate reductase activity. Involved in several processes, including positive regulation of nitric-oxide synthase activity; tetrahydrobiopterin biosynthetic process; and tetrahydrofolate interconversion. Located in mitochondrion and nucleus. Is expressed in several structures, including alimentary system; genitourinary system; hemolymphoid system; integumental system; and nervous system. Human ortholog(s) of this gene implicated in acute lymphoblastic leukemia. Orthologous to several human genes including DHFRP1 (dihydrofolate reductase pseudogene 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in liver E14 (RPKM 9.4), liver E14.5 (RPKM 7.0) and 22 other tissues See more
Orthologs: human all
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Genomic context

Location:: 13 C3; 13 47.64 cM

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	13	NC_000079.7 (92491291..92525561)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	13	NC_000079.6 (92354783..92389053)

Chromosome 13 - NC_000079.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Endothelial NOX4 aggravates eNOS uncoupling by decreasing dihydrofolate reductase after subarachnoid hemorrhage.
Title: Endothelial NOX4 aggravates eNOS uncoupling by decreasing dihydrofolate reductase after subarachnoid hemorrhage.
endothelial Rb positively impacts arterial function by supporting vasoprotective endothelial DHFR/nitric oxide pathway activity, leading to reduced abdominal aortic aneurysm development.
Title: Endothelial retinoblastoma protein reduces abdominal aortic aneurysm development via promoting DHFR/NO pathway-mediated vasoprotection.
The study reports arrested hematopoiesis and vascular relaxation defects in mice with a point mutation, Thr136Ala substitution in Dhfr.
Title: Arrested Hematopoiesis and Vascular Relaxation Defects in Mice with a Mutation in Dhfr.
S-nitrosylation of DHFR at cysteine 7 by eNOS-derived NO is crucial for DHFR stability.
Title: Endothelial Nitric Oxide Synthase-Derived Nitric Oxide Prevents Dihydrofolate Reductase Degradation via Promoting S-Nitrosylation.
demonstrate that dihydrofolate reductase activity is also a feature of the mitochondria in both rat and mouse but this is not due to a second enzyme
Title: An active second dihydrofolate reductase enzyme is not a feature of rat and mouse, but they do have activity in their mitochondria.
Robust and processive unfolding/degradation of some substrates with very stable protein domains, including mDHFR and titin(I27) .
Title: Protein unfolding and degradation by the AAA+ Lon protease.
protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency
Title: Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency.
Dhfr has a role in folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation
Title: Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation.
Data reveal a key role for dihydrofolate reductase in eNOS coupling by maintaining the tetrahyrobiopterin (BH4):dihydrobiopterin (BH2) ratio, particularly in conditions of low total biopterin availability.
Title: Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways.
E2F-responsive dihydrofolate reductase promoter regulates the balance between acetylation and methylation of histone H3 lysine 9
Title: Balance between acetylation and methylation of histone H3 lysine 9 on the E2F-responsive dihydrofolate reductase promoter.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Variation

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Alleles

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

Targeted (4)
Chemically induced (ENU) (1)
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC138237P1 (e-PCR)
- UniSTS:270863

NoName (e-PCR)
- UniSTS:237076

NoName (e-PCR)
- UniSTS:237077

RH74744 (e-PCR)
- UniSTS:116549

AW555094 (e-PCR)
- UniSTS:180571

PMC86057P2 (e-PCR)
- UniSTS:273514

L26316 (e-PCR)
- UniSTS:163540

L26316 (e-PCR)
- UniSTS:124887

AI662710 (e-PCR)
- UniSTS:165887

Homology

Homologs of the Dhfr gene: The Dhfr gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.pombe, M.oryzae, and frog.
Orthologs from Annotation Pipeline: 483 organisms have orthologs with human gene Dhfr
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables NADP binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables NADP binding	ISO Inferred from Sequence Orthology more info
enables NADPH binding	ISO Inferred from Sequence Orthology more info
enables RNA binding	IEA Inferred from Electronic Annotation more info
enables dihydrofolate reductase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables dihydrofolate reductase activity	IDA Inferred from Direct Assay more info	PubMed
enables dihydrofolate reductase activity	ISO Inferred from Sequence Orthology more info
enables dihydrofolic acid binding	ISO Inferred from Sequence Orthology more info
enables folic acid binding	ISO Inferred from Sequence Orthology more info
enables mRNA binding	ISO Inferred from Sequence Orthology more info
enables mRNA regulatory element binding translation repressor activity	ISO Inferred from Sequence Orthology more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables sequence-specific mRNA binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in axon regeneration	ISO Inferred from Sequence Orthology more info
involved_in dihydrofolate metabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in dihydrofolate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in folic acid metabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in folic acid metabolic process	ISO Inferred from Sequence Orthology more info
involved_in glycine biosynthetic 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 positive regulation of nitric-oxide synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of removal of superoxide radicals	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to methotrexate	IEA Inferred from Electronic Annotation more info
involved_in tetrahydrobiopterin biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tetrahydrofolate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in tetrahydrofolate biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate interconversion	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrial inner membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrial matrix	ISO Inferred from Sequence Orthology more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: dihydrofolate reductase

NP_034179.1

EC 1.5.1.3

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_010049.3 → NP_034179.1 dihydrofolate reductase

See identical proteins and their annotated locations for NP_034179.1

Status: VALIDATED

Source sequence(s)

AI854085, AK031241, BU058996, CAAA01146114, CB247191

Consensus CDS

CCDS26680.1

UniProtKB/Swiss-Prot

P00375, Q61579

UniProtKB/TrEMBL

Q544T5

Related

ENSMUSP00000022218.5, ENSMUST00000022218.6

Conserved Domains (1) summary

cd00209
Location:5 → 184

DHFR; Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5, ...