DHFR

Protein identityUniProt · HPA

UniProt accession

P00374

Gene

DHFR

Ensembl

ENSG00000228716

Chromosome

5

Canonical length

187 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

187 residues, UniProt reviewed canonical sequence.

>P00374|DHFR
     1  MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS
    61  IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS
   121  VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF
   181  EVYEKND

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DHFR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

56 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DHFR.

Disease | AllUniProt

Conditions DHFR is implicated in, by any mechanism.

• Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) MIM:613839

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 160 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Constitutional megaloblastic anemia with severe neurologic disease

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.88

gnomAD pLI

0.03

gnomAD missense Z

1.01

DepMap mean gene effect

-0.86

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon regeneration
• dihydrofolate metabolic process
• folic acid metabolic process
• negative regulation of translation
• one-carbon metabolic process
• regulation of removal of superoxide radicals
• tetrahydrobiopterin biosynthetic process
• tetrahydrofolate biosynthetic process
• tetrahydrofolate metabolic process
• response to methotrexate

Molecular functions

• dihydrofolate reductase activity
• folic acid binding
• molecular adaptor activity
• mRNA binding
• mRNA regulatory element binding translation repressor activity
• NADP binding
• NADPH binding
• sequence-specific mRNA binding

Cellular components

• cytosol
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Dihydrofolate reductase domain
• Dihydrofolate reductase
• Dihydrofolate reductase-like domain superfamily
• Dihydrofolate reductase
• Dihydrofolate reductase conserved site

KeywordsUniProt

• Cytoplasm
• Mitochondrion
• NADP
• Nucleus
• One-carbon metabolism
• Oxidoreductase
• RNA-binding
• Ubl conjugation
• Methotrexate resistance

InteractionsUniProt · HPA

Protein binding partners of DHFR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SHMT1