Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Dihydrofolate reductase

Gene

DHFR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 DHFRL1.2 Publications

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation7 Publications

Kineticsi

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

    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, mitochondrial (DHFRL1), Dihydrofolate reductase (DHFR)
    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
    Binding sitei10NADP; via amide nitrogen and carbonyl oxygen3 Publications1
    Binding sitei65Substrate1 Publication1
    Binding sitei71Substrate1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi16 – 22NADP3 Publications7
    Nucleotide bindingi55 – 57NADP3 Publications3
    Nucleotide bindingi77 – 79NADP3 Publications3
    Nucleotide bindingi117 – 124NADP3 Publications8

    GO - Molecular functioni

    • dihydrofolate reductase activity Source: UniProtKB
    • drug binding Source: UniProtKB
    • folate reductase activity Source: Reactome
    • folic acid binding Source: BHF-UCL
    • methotrexate binding Source: BHF-UCL
    • mRNA binding Source: UniProtKB
    • NADPH binding Source: BHF-UCL

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Methotrexate resistance, One-carbon metabolism

    Keywords - Ligandi

    NADP, RNA-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS09699-MONOMER.
    BRENDAi1.5.1.3. 2681.
    ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
    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-RKP00374.
    SIGNORiP00374.
    UniPathwayiUPA00077; UER00158.

    Protein family/group databases

    MoonProtiP00374.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dihydrofolate reductase (EC:1.5.1.3)
    Gene namesi
    Name:DHFR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:2861. DHFR.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    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
    Natural variantiVAR_06581880L → F in DHFRD. 1 PublicationCorresponds to variant rs387906619dbSNPEnsembl.1
    Natural variantiVAR_065819153D → V in DHFRD. 1 PublicationCorresponds to variant rs121913223dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    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

    DisGeNETi1719.
    MalaCardsiDHFR.
    MIMi613839. phenotype.
    OpenTargetsiENSG00000228716.
    Orphaneti319651. Constitutional megaloblastic anemia with severe neurologic disease.
    PharmGKBiPA143.

    Chemistry databases

    ChEMBLiCHEMBL202.
    DrugBankiDB00798. Gentamicin.
    DB00563. Methotrexate.
    DB00642. Pemetrexed.
    DB06813. Pralatrexate.
    DB01131. Proguanil.
    DB00205. Pyrimethamine.
    DB00440. Trimethoprim.
    DB01157. Trimetrexate.
    GuidetoPHARMACOLOGYi2603.

    Polymorphism and mutation databases

    BioMutaiDHFR.
    DMDMi118992.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedBy similarity
    ChainiPRO_00001863622 – 187Dihydrofolate reductaseAdd BLAST186

    Proteomic databases

    EPDiP00374.
    MaxQBiP00374.
    PaxDbiP00374.
    PeptideAtlasiP00374.
    PRIDEiP00374.

    2D gel databases

    UCD-2DPAGEP00374.

    PTM databases

    iPTMnetiP00374.
    PhosphoSitePlusiP00374.
    SwissPalmiP00374.

    Expressioni

    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

    BgeeiENSG00000228716.
    CleanExiHS_DHFR.
    ExpressionAtlasiP00374. baseline and differential.
    GenevisibleiP00374. HS.

    Organism-specific databases

    HPAiCAB037129.
    HPA051465.

    Interactioni

    Subunit structurei

    Homodimer.7 Publications

    Protein-protein interaction databases

    BioGridi108065. 10 interactors.
    IntActiP00374. 3 interactors.
    MINTiMINT-5002355.
    STRINGi9606.ENSP00000396308.

    Chemistry databases

    BindingDBiP00374.

    Structurei

    Secondary structure

    1187
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi5 – 11Combined sources7
    Beta strandi16 – 19Combined sources4
    Beta strandi24 – 26Combined sources3
    Helixi29 – 40Combined sources12
    Beta strandi43 – 46Combined sources4
    Beta strandi48 – 54Combined sources7
    Helixi55 – 60Combined sources6
    Helixi63 – 65Combined sources3
    Beta strandi71 – 76Combined sources6
    Beta strandi88 – 93Combined sources6
    Helixi94 – 101Combined sources8
    Turni104 – 109Combined sources6
    Beta strandi110 – 115Combined sources6
    Helixi119 – 126Combined sources8
    Beta strandi128 – 130Combined sources3
    Beta strandi132 – 141Combined sources10
    Beta strandi146 – 148Combined sources3
    Turni154 – 156Combined sources3
    Beta strandi157 – 159Combined sources3
    Beta strandi161 – 163Combined sources3
    Beta strandi171 – 173Combined sources3
    Beta strandi176 – 185Combined sources10

    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[»]
    ProteinModelPortaliP00374.
    SMRiP00374.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP00374.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini4 – 185DHFRPROSITE-ProRule annotationAdd BLAST182

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni31 – 36Substrate binding1 Publication6

    Sequence similaritiesi

    Belongs to the dihydrofolate reductase family.Curated
    Contains 1 DHFR (dihydrofolate reductase) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG1324. Eukaryota.
    COG0262. LUCA.
    GeneTreeiENSGT00390000010283.
    HOGENOMiHOG000040235.
    HOVERGENiHBG000773.
    InParanoidiP00374.
    KOiK00287.
    OMAiNGIKYEY.
    OrthoDBiEOG091G0PRK.
    PhylomeDBiP00374.
    TreeFamiTF317636.

    Family and domain databases

    CDDicd00209. DHFR. 1 hit.
    Gene3Di3.40.430.10. 1 hit.
    InterProiIPR012259. DHFR.
    IPR024072. DHFR-like_dom.
    IPR017925. DHFR_CS.
    IPR001796. DHFR_dom.
    [Graphical view]
    PfamiPF00186. DHFR_1. 1 hit.
    [Graphical view]
    PRINTSiPR00070. DHFR.
    SUPFAMiSSF53597. SSF53597. 1 hit.
    PROSITEiPS00075. DHFR_1. 1 hit.
    PS51330. DHFR_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    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
    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

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    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 rs387906619dbSNPEnsembl.1
    Natural variantiVAR_065819153D → V in DHFRD. 1 PublicationCorresponds to variant rs121913223dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0563521 – 52Missing in isoform 2. 1 PublicationAdd BLAST52

    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.

    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]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    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[»]
    ProteinModelPortaliP00374.
    SMRiP00374.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108065. 10 interactors.
    IntActiP00374. 3 interactors.
    MINTiMINT-5002355.
    STRINGi9606.ENSP00000396308.

    Chemistry databases

    BindingDBiP00374.
    ChEMBLiCHEMBL202.
    DrugBankiDB00798. Gentamicin.
    DB00563. Methotrexate.
    DB00642. Pemetrexed.
    DB06813. Pralatrexate.
    DB01131. Proguanil.
    DB00205. Pyrimethamine.
    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-2DPAGEP00374.

    Proteomic databases

    EPDiP00374.
    MaxQBiP00374.
    PaxDbiP00374.
    PeptideAtlasiP00374.
    PRIDEiP00374.

    Protocols and materials databases

    DNASUi1719.
    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

    CTDi1719.
    DisGeNETi1719.
    GeneCardsiDHFR.
    HGNCiHGNC:2861. DHFR.
    HPAiCAB037129.
    HPA051465.
    MalaCardsiDHFR.
    MIMi126060. gene.
    613839. phenotype.
    neXtProtiNX_P00374.
    OpenTargetsiENSG00000228716.
    Orphaneti319651. Constitutional megaloblastic anemia with severe neurologic disease.
    PharmGKBiPA143.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1324. Eukaryota.
    COG0262. LUCA.
    GeneTreeiENSGT00390000010283.
    HOGENOMiHOG000040235.
    HOVERGENiHBG000773.
    InParanoidiP00374.
    KOiK00287.
    OMAiNGIKYEY.
    OrthoDBiEOG091G0PRK.
    PhylomeDBiP00374.
    TreeFamiTF317636.

    Enzyme and pathway databases

    UniPathwayiUPA00077; UER00158.
    BioCyciZFISH:HS09699-MONOMER.
    BRENDAi1.5.1.3. 2681.
    ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
    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-RKP00374.
    SIGNORiP00374.

    Miscellaneous databases

    ChiTaRSiDHFR. human.
    EvolutionaryTraceiP00374.
    GeneWikiiDihydrofolate_reductase.
    GenomeRNAii1719.
    PROiP00374.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000228716.
    CleanExiHS_DHFR.
    ExpressionAtlasiP00374. baseline and differential.
    GenevisibleiP00374. HS.

    Family and domain databases

    CDDicd00209. DHFR. 1 hit.
    Gene3Di3.40.430.10. 1 hit.
    InterProiIPR012259. DHFR.
    IPR024072. DHFR-like_dom.
    IPR017925. DHFR_CS.
    IPR001796. DHFR_dom.
    [Graphical view]
    PfamiPF00186. DHFR_1. 1 hit.
    [Graphical view]
    PRINTSiPR00070. DHFR.
    SUPFAMiSSF53597. SSF53597. 1 hit.
    PROSITEiPS00075. DHFR_1. 1 hit.
    PS51330. DHFR_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiDYR_HUMAN
    AccessioniPrimary (citable) accession number: P00374
    Secondary accession number(s): B4DDD2, Q14130, Q6IRW8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: January 23, 2007
    Last modified: November 2, 2016
    This is version 187 of the entry and version 2 of the sequence. [Complete history]
    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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.