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UniProtKB - P00374 (DYR_HUMAN)

Entry version 207 (13 Feb 2019)
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.
    Proteins known to be involved in this subpathway in this organism are:
    1. Dihydrofolate reductase (DHFR), Dihydrofolate reductase 2, mitochondrial (DHFR2)
    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 ‘Function’ 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 ‘Function’ 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

    View the complete GO annotation on QuickGO ...

    GO - Biological processi

    View the complete GO annotation on QuickGO ...

    <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

    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-539107 Activation of E2F1 target genes at G1/S

    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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    <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

    Eukaryotic Pathogen Database Resources

    More...    EuPathDBi    		HostDB:ENSG00000228716.6

    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

    <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

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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 mutations 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.
    See also OMIM:613839
    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 mutation

    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

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...    ChEMBLi    		CHEMBL202

    Drug and drug target database

    More...    DrugBanki    		DB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
    DB08878 Aminopterin
    DB03886 Biopterin
    DB00798 Gentamicin
    DB00563 Methotrexate
    DB00157 NADH
    DB00642 Pemetrexed
    DB06813 Pralatrexate
    DB01131 Proguanil
    DB00205 Pyrimethamine
    DB03351 Sri-9439
    DB03060 Sri-9662
    DB00440 Trimethoprim
    DB01157 Trimetrexate

    IUPHAR/BPS Guide to PHARMACOLOGY

    More...    GuidetoPHARMACOLOGYi    		2603

    Polymorphism and mutation 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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001863621 – 187Dihydrofolate reductaseAdd BLAST187

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...    EPDi    		P00374

    jPOST - Japan Proteome Standard Repository/Database

    More...    jPOSTi    		P00374

    MaxQB - The MaxQuant DataBase

    More...    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 human proteome resource

    More...    ProteomicsDBi    		51237

    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 232 organ(s), highest expression level in buccal mucosa cell

    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    		CAB037129
    HPA051465

    <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, 17 interactors

    Protein interaction database and analysis system

    More...    IntActi    		P00374, 9 interactors

    Molecular INTeraction database

    More...    MINTi    		P00374

    STRING: functional protein association networks

    More...    STRINGi    		9606.ENSP00000396308

    Chemistry databases

    BindingDB database of measured binding affinities

    More...    BindingDBi    		P00374

    <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

    Select the link destinations:

    Protein Data Bank Europe

    More...    PDBei

    Protein Data Bank RCSB

    More...    RCSB PDBi

    Protein Data Bank Japan

    More...    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[»]
    6DAVX-ray1.55A/B1-187[»]
    6DE4X-ray2.41A/B2-187[»]

    Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

    More...    ProteinModelPortali    		P00374

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

    More...    SMRi    		P00374

    Database of comparative protein structure models

    More...    ModBasei    		Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...    MobiDBi    		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
    COG0262 LUCA

    Ensembl GeneTree

    More...    GeneTreei    		ENSGT00390000010283

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...    HOGENOMi    		HOG000040235

    The HOVERGEN Database of Homologous Vertebrate Genes

    More...    HOVERGENi    		HBG000773

    InParanoid: Eukaryotic Ortholog Groups

    More...    InParanoidi    		P00374

    KEGG Orthology (KO)

    More...    KOi    		K00287

    Identification of Orthologs from Complete Genome Data

    More...    OMAi    		RDNQLPW

    Database of Orthologous Groups

    More...    OrthoDBi    		1489621at2759

    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
    IPR024072 DHFR-like_dom_sf
    IPR017925 DHFR_CS
    IPR001796 DHFR_dom

    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>.<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 'canonical' 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.

    Note: No experimental confirmation available.
    Show »
    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:1 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

    More...    EMBLi

    GenBank nucleotide sequence database

    More...    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...    DDBJi
    Links Updated
    		J00140 mRNA Translation: AAA58485.1
    V00507 mRNA Translation: CAA23765.1
    J00139
    , K01612, K01613, J00138, K01614 Genomic DNA Translation: AAA58484.1
    X00855
    , X00856, X00857, X00858, 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

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

    Protein sequence database of the Protein Information Resource

    More...    PIRi    		A22551 RDHUD

    NCBI Reference Sequences

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

    UniGene gene-oriented nucleotide sequence clusters

    More...    UniGenei    		Hs.592364
    Hs.648635

    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

    More...    GeneIDi    		1719

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...    KEGGi    		hsa:1719

    UCSC genome browser

    More...    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
    , K01612, K01613, J00138, K01614 Genomic DNA Translation: AAA58484.1
    X00855
    , X00856, X00857, X00858, 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]
    UniGeneiHs.592364
    Hs.648635

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    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[»]
    6DAVX-ray1.55A/B1-187[»]
    6DE4X-ray2.41A/B2-187[»]
    ProteinModelPortaliP00374
    SMRiP00374
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108065, 17 interactors
    IntActiP00374, 9 interactors
    MINTiP00374
    STRINGi9606.ENSP00000396308

    Chemistry databases

    BindingDBiP00374
    ChEMBLiCHEMBL202
    DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
    DB08878 Aminopterin
    DB03886 Biopterin
    DB00798 Gentamicin
    DB00563 Methotrexate
    DB00157 NADH
    DB00642 Pemetrexed
    DB06813 Pralatrexate
    DB01131 Proguanil
    DB00205 Pyrimethamine
    DB03351 Sri-9439
    DB03060 Sri-9662
    DB00440 Trimethoprim
    DB01157 Trimetrexate
    GuidetoPHARMACOLOGYi2603

    Protein family/group databases

    MoonProtiP00374

    PTM databases

    iPTMnetiP00374
    PhosphoSitePlusiP00374
    SwissPalmiP00374

    Polymorphism and mutation databases

    BioMutaiDHFR
    DMDMi118992

    2D gel databases

    UCD-2DPAGEiP00374

    Proteomic databases

    EPDiP00374
    jPOSTiP00374
    MaxQBiP00374
    PaxDbiP00374
    PeptideAtlasiP00374
    PRIDEiP00374
    ProteomicsDBi51237

    Protocols and materials databases

    The DNASU plasmid repository

    More...    DNASUi    		1719
    Structural Biology KnowledgebaseSearch...

    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
    EuPathDBiHostDB:ENSG00000228716.6

    GeneCards: human genes, protein and diseases

    More...    GeneCardsi    		DHFR
    HGNCiHGNC:2861 DHFR
    HPAiCAB037129
    HPA051465
    MalaCardsiDHFR
    MIMi126060 gene
    613839 phenotype
    neXtProtiNX_P00374
    OpenTargetsiENSG00000228716
    Orphaneti319651 Constitutional megaloblastic anemia with severe neurologic disease
    PharmGKBiPA143

    GenAtlas: human gene database

    More...    GenAtlasi    		Search...

    Phylogenomic databases

    eggNOGiKOG1324 Eukaryota
    COG0262 LUCA
    GeneTreeiENSGT00390000010283
    HOGENOMiHOG000040235
    HOVERGENiHBG000773
    InParanoidiP00374
    KOiK00287
    OMAiRDNQLPW
    OrthoDBi1489621at2759
    PhylomeDBiP00374
    TreeFamiTF317636

    Enzyme and pathway databases

    UniPathwayi
    UPA00077;UER00158

    BioCyciMetaCyc:HS09699-MONOMER
    BRENDAi1.5.1.3 2681
    ReactomeiR-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
    R-HSA-196757 Metabolism of folate and pterines
    R-HSA-539107 Activation of E2F1 target genes at G1/S
    SABIO-RKiP00374
    SIGNORiP00374

    Miscellaneous databases

    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

    Protein Ontology

    More...    PROi    		PR:P00374

    The Stanford Online Universal Resource for Clones and ESTs

    More...    SOURCEi    		Search...

    Gene expression databases

    BgeeiENSG00000228716 Expressed in 232 organ(s), highest expression level in buccal mucosa cell
    ExpressionAtlasiP00374 baseline and differential
    GenevisibleiP00374 HS

    Family and domain databases

    CDDicd00209 DHFR, 1 hit
    Gene3Di3.40.430.10, 1 hit
    InterProiView protein in InterPro
    IPR024072 DHFR-like_dom_sf
    IPR017925 DHFR_CS
    IPR001796 DHFR_dom
    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

    ProtoNet; Automatic hierarchical classification of proteins

    More...    ProtoNeti    		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: February 13, 2019
    This is version 207 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, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families
    3. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    4. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    5. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    6. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    7. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    UniProt is an ELIXIR core data resource
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