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Entry version 222 (29 Sep 2021)
Sequence version 2 (23 Jan 2007)
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Protein

Dihydrofolate reductase

Gene

DHFR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2.

2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=2.7 µM for dihydrofolate3 Publications
  2. KM=4.0 µM for NADPH3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate. This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei10NADP; via amide nitrogen and carbonyl oxygen3 Publications1
Binding sitei65Substrate1 Publication1
Binding sitei71Substrate1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi16 – 22NADP3 Publications7
Nucleotide bindingi55 – 57NADP3 Publications3
Nucleotide bindingi77 – 79NADP3 Publications3
Nucleotide bindingi117 – 124NADP3 Publications8

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionOxidoreductase, RNA-binding
Biological processMethotrexate resistance, One-carbon metabolism
LigandNADP

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

More...
BioCyci
MetaCyc:HS09699-MONOMER

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
1.5.1.3, 2681

Pathway Commons web resource for biological pathway data

More...
PathwayCommonsi
P00374

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-1474151, Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-HSA-196757, Metabolism of folate and pterines
R-HSA-69205, G1/S-Specific Transcription

SABIO-RK: Biochemical Reaction Kinetics Database

More...
SABIO-RKi
P00374

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P00374

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00077;UER00158

Protein family/group databases

MoonProt database of moonlighting proteins

More...
MoonProti
P00374

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:DHFR
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 5

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:2861, DHFR

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
126060, gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P00374

Eukaryotic Pathogen, Vector and Host Database Resources

More...
VEuPathDBi
HostDB:ENSG00000228716

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_06581880L → F in DHFRD. 1 PublicationCorresponds to variant dbSNP:rs387906619EnsemblClinVar.1
Natural variantiVAR_065819153D → V in DHFRD. 1 PublicationCorresponds to variant dbSNP:rs121913223EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi23L → F, W or Y: Decreases affinity for NADP and dihydrofolate over 10-fold. 2 Publications1
Mutagenesisi23L → R: Strongly decreased affinity for methotrexate. Decreases catalytic rate constant 200-fold. Decreases affinity for NADP and dihydrofolate over 10-fold. 2 Publications1
Mutagenesisi32F → R: Reduces catalytic rate 5-fold. Reduces affinity for dihydrofolate 9-fold; when associated with E-36. 1 Publication1
Mutagenesisi36Q → E: Reduces catalytic rate 2-fold. Reduces affinity for dihydrofolate 9-fold; when associated with R-32. 3 Publications1
Mutagenesisi36Q → K: Increases affinity for dihydrofolate about 3-fold. Reduces affinity for NADPH about 3-fold. 3 Publications1
Mutagenesisi36Q → S: Increases affinity for dihydrofolate about 2-fold. No effect on affinity for NADPH. 3 Publications1
Mutagenesisi65N → F: Increases affinity for dihydrofolate about 3-fold. No effect on affinity for NADPH. 2 Publications1
Mutagenesisi65N → S: Increases affinity for dihydrofolate about 15-fold. No effect on affinity for NADPH. 2 Publications1

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...
DisGeNETi
1719

MalaCards human disease database

More...
MalaCardsi
DHFR
MIMi613839, phenotype

Open Targets

More...
OpenTargetsi
ENSG00000228716

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
319651, Constitutional megaloblastic anemia with severe neurologic disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA143

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
P00374, Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL202

Drug and drug target database

More...
DrugBanki
DB08642, (2R,6S)-6-{[methyl(3,4,5-trimethoxyphenyl)amino]methyl}-1,2,5,6,7,8-hexahydroquinazoline-2,4-diamine
DB08448, (4aS)-5-[(2,4-diaminopteridin-6-yl)methyl]-4a,5-dihydro-2H-dibenzo[b,f]azepin-8-ol
DB03125, 2,4-Diamino-5-(3,4,5-Trimethoxy-Benzyl)-Pyrimidin-1-Ium
DB02104, 2,4-Diamino-5-Methyl-6-[(3,4,5-Trimethoxy-N-Methylanilino)Methyl]Pyrido[2,3-D]Pyrimidine
DB02427, 2,4-Diamino-6-[N-(2',5'-Dimethoxybenzyl)-N-Methylamino]Quinazoline
DB02919, 2,4-Diamino-6-[N-(3',4',5'-Trimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine
DB03987, 2,4-Diamino-6-[N-(3',5'-Dimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine
DB07144, 5-[(3R)-3-(5-methoxy-2',6'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB07142, 5-[(3R)-3-(5-methoxy-3',5'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB07141, 5-[(3R)-3-(5-methoxy-4'-methylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB07140, 5-[(3R)-3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB08234, 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine
DB02559, 6-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-Diamine
DB08406, [N-(2,4-DIAMINOPTERIDIN-6-YL)-METHYL]-DIBENZ[B,F]AZEPINE
DB08878, Aminopterin
DB03886, Biopterin
DB00158, Folic acid
DB00798, Gentamicin
DB06358, Iclaprim
DB00555, Lamotrigine
DB00563, Methotrexate
DB02583, N6-(2,5-Dimethoxy-Benzyl)-N6-Methyl-Pyrido[2,3-D]Pyrimidine-2,4,6-Triamine
DB00157, NADH
DB03461, Nicotinamide adenine dinucleotide phosphate
DB00642, Pemetrexed
DB03695, Piritrexim
DB06813, Pralatrexate
DB01131, Proguanil
DB00205, Pyrimethamine
DB03351, Sri-9439
DB03060, Sri-9662
DB01157, Trimetrexate

DrugCentral

More...
DrugCentrali
P00374

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2603

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
DHFR

Domain mapping of disease mutations (DMDM)

More...
DMDMi
118992

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001863621 – 187Dihydrofolate reductaseAdd BLAST187

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P00374

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P00374

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P00374

MaxQB - The MaxQuant DataBase

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MaxQBi
P00374

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P00374

PeptideAtlas

More...
PeptideAtlasi
P00374

PRoteomics IDEntifications database

More...
PRIDEi
P00374

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
3847
51237 [P00374-1]

2D gel databases

University College Dublin 2-DE Proteome Database

More...
UCD-2DPAGEi
P00374

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P00374

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P00374

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
P00374

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed in fetal and adult tissues, including throughout the fetal and adult brains and whole blood. Expression is higher in the adult brain than in the fetal brain.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000228716, Expressed in buccal mucosa cell and 248 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P00374, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P00374, HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000228716, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.

7 Publications

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...
BioGRIDi
108065, 34 interactors

Protein interaction database and analysis system

More...
IntActi
P00374, 9 interactors

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000396308

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P00374

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
P00374, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1187
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Biological Magnetic Resonance Data Bank

More...
BMRBi
P00374

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P00374

Database of comparative protein structure models

More...
ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P00374

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini4 – 185DHFRPROSITE-ProRule annotationAdd BLAST182

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni31 – 36Substrate binding1 Publication6

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the dihydrofolate reductase family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG1324, Eukaryota

Ensembl GeneTree

More...
GeneTreei
ENSGT00390000010283

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_043966_2_3_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P00374

Identification of Orthologs from Complete Genome Data

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OMAi
RDNQLPW

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P00374

TreeFam database of animal gene trees

More...
TreeFami
TF317636

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00209, DHFR, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.40.430.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR012259, DHFR
IPR024072, DHFR-like_dom_sf
IPR017925, DHFR_CS
IPR001796, DHFR_dom

The PANTHER Classification System

More...
PANTHERi
PTHR48069, PTHR48069, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00186, DHFR_1, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF53597, SSF53597, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00075, DHFR_1, 1 hit
PS51330, DHFR_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P00374-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL
60 70 80 90 100
VIMGKKTWFS IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL
110 120 130 140 150
TEQPELANKV DMVWIVGGSS VYKEAMNHPG HLKLFVTRIM QDFESDTFFP
160 170 180
EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF EVYEKND
Length:187
Mass (Da):21,453
Last modified:January 23, 2007 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iEBDF3D1EC73E1566
GO
Isoform 2 (identifier: P00374-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.

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Length:135
Mass (Da):15,672
Checksum:i92704AAABEE1EF40
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DM58B4DM58_HUMAN
Dihydrofolate reductase
DHFR
129Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti113V → L in AAH70280 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06581880L → F in DHFRD. 1 PublicationCorresponds to variant dbSNP:rs387906619EnsemblClinVar.1
Natural variantiVAR_065819153D → V in DHFRD. 1 PublicationCorresponds to variant dbSNP:rs121913223EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0563521 – 52Missing in isoform 2. 1 PublicationAdd BLAST52

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
J00140 mRNA Translation: AAA58485.1
V00507 mRNA Translation: CAA23765.1
J00139 K01614 Genomic DNA Translation: AAA58484.1
X00855 X00859 Genomic DNA Translation: CAA25409.1
AK293146 mRNA Translation: BAG56693.1
AC008434 Genomic DNA No translation available.
AC010270 Genomic DNA No translation available.
BC000192 mRNA Translation: AAH00192.1
BC003584 mRNA Translation: AAH03584.2
BC070280 mRNA Translation: AAH70280.1
BC071996 mRNA Translation: AAH71996.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS47240.1 [P00374-1]
CCDS78028.1 [P00374-2]

Protein sequence database of the Protein Information Resource

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PIRi
A22551, RDHUD

NCBI Reference Sequences

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RefSeqi
NP_000782.1, NM_000791.3 [P00374-1]
NP_001277283.1, NM_001290354.1 [P00374-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000439211; ENSP00000396308; ENSG00000228716 [P00374-1]
ENST00000504396; ENSP00000421334; ENSG00000228716 [P00374-2]
ENST00000505337; ENSP00000426474; ENSG00000228716 [P00374-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
1719

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:1719

UCSC genome browser

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UCSCi
uc003kgy.2, human [P00374-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

Dihydrofolate reductase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J00140 mRNA Translation: AAA58485.1
V00507 mRNA Translation: CAA23765.1
J00139 K01614 Genomic DNA Translation: AAA58484.1
X00855 X00859 Genomic DNA Translation: CAA25409.1
AK293146 mRNA Translation: BAG56693.1
AC008434 Genomic DNA No translation available.
AC010270 Genomic DNA No translation available.
BC000192 mRNA Translation: AAH00192.1
BC003584 mRNA Translation: AAH03584.2
BC070280 mRNA Translation: AAH70280.1
BC071996 mRNA Translation: AAH71996.1
CCDSiCCDS47240.1 [P00374-1]
CCDS78028.1 [P00374-2]
PIRiA22551, RDHUD
RefSeqiNP_000782.1, NM_000791.3 [P00374-1]
NP_001277283.1, NM_001290354.1 [P00374-2]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BOZX-ray2.10A2-187[»]
1DHFX-ray2.30A/B2-187[»]
1DLRX-ray2.30A2-187[»]
1DLSX-ray2.30A2-187[»]
1DRFX-ray2.00A2-187[»]
1HFPX-ray2.10A2-187[»]
1HFQX-ray2.10A2-187[»]
1HFRX-ray2.10A2-187[»]
1KMSX-ray1.09A2-187[»]
1KMVX-ray1.05A2-187[»]
1MVSX-ray1.90A1-187[»]
1MVTX-ray1.80A1-187[»]
1OHJX-ray2.50A2-187[»]
1OHKX-ray2.50A2-187[»]
1PD8X-ray2.10A2-187[»]
1PD9X-ray2.20A2-187[»]
1PDBX-ray2.20A2-187[»]
1S3UX-ray2.50A2-187[»]
1S3VX-ray1.80A2-187[»]
1S3WX-ray1.90A2-187[»]
1U71X-ray2.20A2-187[»]
1U72X-ray1.90A2-187[»]
1YHONMR-A2-187[»]
2C2SX-ray1.40A/B2-187[»]
2C2TX-ray1.50A/B2-187[»]
2DHFX-ray2.30A/B2-187[»]
2W3AX-ray1.50A/B1-187[»]
2W3BX-ray1.27A/B1-187[»]
2W3MX-ray1.60A/B1-187[»]
3EIGX-ray1.70A2-187[»]
3F8YX-ray1.45A1-187[»]
3F8ZX-ray2.01A1-187[»]
3F91X-ray1.90A1-187[»]
3FS6X-ray1.23A1-187[»]
3GHCX-ray1.30A2-187[»]
3GHVX-ray1.30A2-187[»]
3GHWX-ray1.24A2-187[»]
3GI2X-ray1.53A1-187[»]
3GYFX-ray1.70A1-187[»]
3L3RX-ray2.00A2-187[»]
3N0HX-ray1.92A2-187[»]
3NTZX-ray1.35A2-187[»]
3NU0X-ray1.35A2-187[»]
3NXOX-ray1.35A2-187[»]
3NXRX-ray1.35A2-187[»]
3NXTX-ray1.70A2-187[»]
3NXVX-ray1.90A2-187[»]
3NXXX-ray1.35A2-187[»]
3NXYX-ray1.90A2-187[»]
3NZDX-ray1.80A2-187[»]
3OAFX-ray1.70A2-187[»]
3S3VX-ray1.53A2-187[»]
3S7AX-ray1.80A2-187[»]
4DDRX-ray2.05A2-187[»]
4G95X-ray1.35A2-187[»]
4KAKX-ray1.80A/B2-187[»]
4KBNX-ray1.84A/B2-187[»]
4KD7X-ray2.72A/B2-187[»]
4KEBX-ray1.45A/B2-187[»]
4KFJX-ray1.76A/B2-187[»]
4M6JX-ray1.20A1-187[»]
4M6KX-ray1.40A1-187[»]
4M6LX-ray1.70A1-187[»]
4QHVX-ray1.61A2-187[»]
4QJCX-ray1.62A2-187[»]
5HPBX-ray1.65A2-187[»]
5HQYX-ray1.46A2-187[»]
5HQZX-ray1.46A2-187[»]
5HSRX-ray1.21A2-187[»]
5HSUX-ray1.46A2-187[»]
5HT4X-ray1.60A2-187[»]
5HT5X-ray1.90A2-187[»]
5HUIX-ray1.46A2-187[»]
5HVBX-ray1.60A2-187[»]
5HVEX-ray1.46A2-187[»]
6A7CX-ray2.06A2-187[»]
6A7EX-ray1.85A2-187[»]
6DAVX-ray1.55A/B1-187[»]
6DE4X-ray2.41A/B2-187[»]
6VCJX-ray2.34A/B/C/D1-187[»]
7ESEX-ray1.85A1-187[»]
BMRBiP00374
SMRiP00374
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi108065, 34 interactors
IntActiP00374, 9 interactors
STRINGi9606.ENSP00000396308

Chemistry databases

BindingDBiP00374
ChEMBLiCHEMBL202
DrugBankiDB08642, (2R,6S)-6-{[methyl(3,4,5-trimethoxyphenyl)amino]methyl}-1,2,5,6,7,8-hexahydroquinazoline-2,4-diamine
DB08448, (4aS)-5-[(2,4-diaminopteridin-6-yl)methyl]-4a,5-dihydro-2H-dibenzo[b,f]azepin-8-ol
DB03125, 2,4-Diamino-5-(3,4,5-Trimethoxy-Benzyl)-Pyrimidin-1-Ium
DB02104, 2,4-Diamino-5-Methyl-6-[(3,4,5-Trimethoxy-N-Methylanilino)Methyl]Pyrido[2,3-D]Pyrimidine
DB02427, 2,4-Diamino-6-[N-(2',5'-Dimethoxybenzyl)-N-Methylamino]Quinazoline
DB02919, 2,4-Diamino-6-[N-(3',4',5'-Trimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine
DB03987, 2,4-Diamino-6-[N-(3',5'-Dimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine
DB07144, 5-[(3R)-3-(5-methoxy-2',6'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB07142, 5-[(3R)-3-(5-methoxy-3',5'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB07141, 5-[(3R)-3-(5-methoxy-4'-methylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB07140, 5-[(3R)-3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
DB08234, 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine
DB02559, 6-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-Diamine
DB08406, [N-(2,4-DIAMINOPTERIDIN-6-YL)-METHYL]-DIBENZ[B,F]AZEPINE
DB08878, Aminopterin
DB03886, Biopterin
DB00158, Folic acid
DB00798, Gentamicin
DB06358, Iclaprim
DB00555, Lamotrigine
DB00563, Methotrexate
DB02583, N6-(2,5-Dimethoxy-Benzyl)-N6-Methyl-Pyrido[2,3-D]Pyrimidine-2,4,6-Triamine
DB00157, NADH
DB03461, Nicotinamide adenine dinucleotide phosphate
DB00642, Pemetrexed
DB03695, Piritrexim
DB06813, Pralatrexate
DB01131, Proguanil
DB00205, Pyrimethamine
DB03351, Sri-9439
DB03060, Sri-9662
DB01157, Trimetrexate
DrugCentraliP00374
GuidetoPHARMACOLOGYi2603

Protein family/group databases

MoonProtiP00374

PTM databases

iPTMnetiP00374
PhosphoSitePlusiP00374
SwissPalmiP00374

Genetic variation databases

BioMutaiDHFR
DMDMi118992

2D gel databases

UCD-2DPAGEiP00374

Proteomic databases

EPDiP00374
jPOSTiP00374
MassIVEiP00374
MaxQBiP00374
PaxDbiP00374
PeptideAtlasiP00374
PRIDEiP00374
ProteomicsDBi3847
51237 [P00374-1]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
24646, 306 antibodies

The DNASU plasmid repository

More...
DNASUi
1719

Genome annotation databases

EnsembliENST00000439211; ENSP00000396308; ENSG00000228716 [P00374-1]
ENST00000504396; ENSP00000421334; ENSG00000228716 [P00374-2]
ENST00000505337; ENSP00000426474; ENSG00000228716 [P00374-1]
GeneIDi1719
KEGGihsa:1719
UCSCiuc003kgy.2, human [P00374-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
1719
DisGeNETi1719

GeneCards: human genes, protein and diseases

More...
GeneCardsi
DHFR
HGNCiHGNC:2861, DHFR
HPAiENSG00000228716, Low tissue specificity
MalaCardsiDHFR
MIMi126060, gene
613839, phenotype
neXtProtiNX_P00374
OpenTargetsiENSG00000228716
Orphaneti319651, Constitutional megaloblastic anemia with severe neurologic disease
PharmGKBiPA143
VEuPathDBiHostDB:ENSG00000228716

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1324, Eukaryota
GeneTreeiENSGT00390000010283
HOGENOMiCLU_043966_2_3_1
InParanoidiP00374
OMAiRDNQLPW
PhylomeDBiP00374
TreeFamiTF317636

Enzyme and pathway databases

UniPathwayiUPA00077;UER00158
BioCyciMetaCyc:HS09699-MONOMER
BRENDAi1.5.1.3, 2681
PathwayCommonsiP00374
ReactomeiR-HSA-1474151, Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-HSA-196757, Metabolism of folate and pterines
R-HSA-69205, G1/S-Specific Transcription
SABIO-RKiP00374
SIGNORiP00374

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
1719, 572 hits in 1025 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
DHFR, human
EvolutionaryTraceiP00374

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
Dihydrofolate_reductase

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
1719
PharosiP00374, Tclin

Protein Ontology

More...
PROi
PR:P00374
RNActiP00374, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000228716, Expressed in buccal mucosa cell and 248 other tissues
ExpressionAtlasiP00374, baseline and differential
GenevisibleiP00374, HS

Family and domain databases

CDDicd00209, DHFR, 1 hit
Gene3Di3.40.430.10, 1 hit
InterProiView protein in InterPro
IPR012259, DHFR
IPR024072, DHFR-like_dom_sf
IPR017925, DHFR_CS
IPR001796, DHFR_dom
PANTHERiPTHR48069, PTHR48069, 1 hit
PfamiView protein in Pfam
PF00186, DHFR_1, 1 hit
SUPFAMiSSF53597, SSF53597, 1 hit
PROSITEiView protein in PROSITE
PS00075, DHFR_1, 1 hit
PS51330, DHFR_2, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiDYR_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P00374
Secondary accession number(s): B4DDD2, Q14130, Q6IRW8
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: September 29, 2021
This is version 222 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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