Dhfr dihydrofolate reductase [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Dhfrprovided by RGD
Official Full Name: dihydrofolate reductaseprovided by RGD
Primary source: RGD:2500
See related: Ensembl:ENSRNOG00000013521 AllianceGenome:RGD:2500
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Dhfr1
Summary: Enables NADP binding activity; dihydrofolate reductase activity; and dihydrofolic acid binding activity. Involved in several processes, including axon regeneration; folic acid-containing compound metabolic process; and response to methotrexate. Located in mitochondrion. Human ortholog(s) of this gene implicated in acute lymphoblastic leukemia. Orthologous to several human genes including DHFR2 (dihydrofolate reductase 2) and DHFRP1 (dihydrofolate reductase pseudogene 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Kidney (RPKM 450.8), Liver (RPKM 427.1) and 5 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 2q12

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	2	NC_086020.1 (25320895..25346004)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	2	NC_051337.1 (23585876..23611199)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	2	NC_005101.4 (21931887..21958927)

Chromosome 2 - NC_086020.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
Design of analogs of piritrexim as inhibitors of this enzyme.
Title: Design, synthesis, and antifolate activity of new analogues of piritrexim and other diaminopyrimidine dihydrofolate reductase inhibitors with omega-carboxyalkoxy or omega-carboxy-1-alkynyl substitution in the side chain.
Ras activation has a role in nicotine- potentiated amplification of the dihydrofolate reductase gene in rat lung epithelial cells
Title: Persistent nicotine treatment potentiates amplification of the dihydrofolate reductase gene in rat lung epithelial cells as a consequence of Ras activation.

Submit: New GeneRIF Correction

General gene information

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Markers

BE121398 (e-PCR)
- UniSTS:248080

RH134136 (e-PCR)
- UniSTS:217418

BI302236 (e-PCR)
- UniSTS:247628

RH133371 (e-PCR)
- UniSTS:216654

AW555094 (e-PCR)
- UniSTS:180571

RH141424 (e-PCR)
- UniSTS:223418

RH128352 (e-PCR)
- UniSTS:211660

RH141201 (e-PCR)
- UniSTS:223197

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables NADP binding	IBA Inferred from Biological aspect of Ancestor more info
enables NADP binding	IDA Inferred from Direct Assay more info	PubMed
enables NADPH binding	ISO Inferred from Sequence Orthology more info
enables dihydrofolate reductase activity	IBA Inferred from Biological aspect of Ancestor more info
enables dihydrofolate reductase activity	IDA Inferred from Direct Assay more info	PubMed
enables dihydrofolate reductase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables dihydrofolate reductase activity	ISO Inferred from Sequence Orthology more info
enables dihydrofolate reductase activity	ISS Inferred from Sequence or Structural Similarity more info
enables dihydrofolic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables folic acid binding	ISO Inferred from Sequence Orthology more info
enables mRNA binding	ISO Inferred from Sequence Orthology more info
enables mRNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables mRNA regulatory element binding translation repressor activity	ISO Inferred from Sequence Orthology more info
enables sequence-specific mRNA binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in axon regeneration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dihydrofolate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in dihydrofolate metabolic process	IDA Inferred from Direct Assay 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
involved_in folic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glycine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of translation	ISO Inferred from Sequence Orthology more info
involved_in regulation of removal of superoxide radicals	ISO Inferred from Sequence Orthology more info
involved_in response to methotrexate	IEA Inferred from Electronic Annotation more info
involved_in response to nicotine	IEP Inferred from Expression Pattern more info	PubMed
involved_in tetrahydrobiopterin biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in tetrahydrofolate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in tetrahydrofolate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in tetrahydrofolate biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate interconversion	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate metabolic process	ISS Inferred from Sequence or Structural Similarity more info

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
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
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	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: dihydrofolate reductase

Names: Dihydrofolate reductase 1 (active)

NP_569084.1

EC 1.5.1.3

XP_038957638.1

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_130400.2 → NP_569084.1 dihydrofolate reductase

See identical proteins and their annotated locations for NP_569084.1

Status: PROVISIONAL

Source sequence(s)

AF318150

UniProtKB/Swiss-Prot

Q920D2

UniProtKB/TrEMBL

B0BMV8

Related

ENSRNOP00000018259.3, ENSRNOT00000018259.6

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, ...

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086020.1 Reference GRCr8

Range

25320895..25346004

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039101710.2 → XP_038957638.1 dihydrofolate reductase isoform X1

Conserved Domains (1) summary

cd00209
Location:5 → 85

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, ...