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Protein

Dihydrofolate reductase 2, mitochondrial

Gene

DHFR2

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

Functioni

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.2 Publications

Miscellaneous

Humans have acquired two dihydrofolate reductase enzymes during their evolution, DHFR and DHFR2. In contrast to human, mice and brown rats have just one.1 Publication

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation1 Publication

Kineticsi

  1. KM=209 µM for dihydrofolate1 Publication
  2. KM=20 µM for NADPH1 Publication

    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 2, mitochondrial (DHFR2), 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 oxygenBy similarity1
    Binding sitei71SubstrateBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi16 – 22NADPBy similarity7
    Nucleotide bindingi55 – 57NADPBy similarity3
    Nucleotide bindingi77 – 79NADPBy similarity3
    Nucleotide bindingi117 – 124NADPBy similarity8

    GO - Molecular functioni

    • dihydrofolate reductase activity Source: UniProtKB
    • mRNA binding Source: UniProtKB
    • NADP binding Source: GO_Central

    GO - Biological processi

    Keywordsi

    Molecular functionOxidoreductase
    Biological processOne-carbon metabolism
    LigandNADP

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000178700-MONOMER
    ReactomeiR-HSA-196757 Metabolism of folate and pterines
    UniPathwayi
    UPA00077;UER00158

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dihydrofolate reductase 2, mitochondrial
    Alternative name(s):
    Dihydrofolate reductase, mitochondrial (EC:1.5.1.3)
    Dihydrofolate reductase-like protein 1
    Gene namesi
    Name:DHFR2Imported
    Synonyms:DHFRL1, DHFRP4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 3

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000178700.7
    HGNCiHGNC:27309 DHFR2
    MIMi616588 gene
    neXtProtiNX_Q86XF0

    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

    Membrane, Mitochondrion, Mitochondrion inner membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi200895
    OpenTargetsiENSG00000178700
    PharmGKBiPA134889916

    Polymorphism and mutation databases

    BioMutaiDHFRL1
    DMDMi74727819

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001863681 – 187Dihydrofolate reductase 2, mitochondrialAdd BLAST187

    Proteomic databases

    EPDiQ86XF0
    MaxQBiQ86XF0
    PaxDbiQ86XF0
    PeptideAtlasiQ86XF0
    PRIDEiQ86XF0
    ProteomicsDBi70273
    TopDownProteomicsiQ86XF0

    PTM databases

    iPTMnetiQ86XF0
    PhosphoSitePlusiQ86XF0

    Expressioni

    Tissue specificityi

    Expressed in numerous cell lines.1 Publication

    Gene expression databases

    BgeeiENSG00000178700 Expressed in 208 organ(s), highest expression level in buccal mucosa cell
    ExpressionAtlasiQ86XF0 baseline and differential
    GenevisibleiQ86XF0 HS

    Organism-specific databases

    HPAiHPA051465

    Interactioni

    Protein-protein interaction databases

    BioGridi128354, 61 interactors
    IntActiQ86XF0, 2 interactors
    STRINGi9606.ENSP00000319170

    Structurei

    3D structure databases

    ProteinModelPortaliQ86XF0
    SMRiQ86XF0
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

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

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni31 – 36Substrate bindingBy similarity6

    Sequence similaritiesi

    Belongs to the dihydrofolate reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1324 Eukaryota
    COG0262 LUCA
    GeneTreeiENSGT00390000010283
    HOGENOMiHOG000040235
    HOVERGENiHBG000773
    InParanoidiQ86XF0
    KOiK00287
    OMAiQYEFQMW
    OrthoDBiEOG091G0PRK
    PhylomeDBiQ86XF0
    TreeFamiTF317636

    Family and domain databases

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

    Sequence (1+)i

    Sequence statusi: Complete.

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

    Q86XF0-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MFLLLNCIVA VSQNMGIGKN GDLPRPPLRN EFRYFQRMTT TSSVEGKQNL
    60 70 80 90 100
    VIMGRKTWFS IPEKNRPLKD RINLVLSREL KEPPQGAHFL ARSLDDALKL
    110 120 130 140 150
    TERPELANKV DMIWIVGGSS VYKEAMNHLG HLKLFVTRIM QDFESDTFFS
    160 170 180
    EIDLEKYKLL PEYPGVLSDV QEGKHIKYKF EVCEKDD
    Length:187
    Mass (Da):21,620
    Last modified:June 1, 2003 - v1
    Checksum:iBA6548FB0F576FF7
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    C9JJ68C9JJ68_HUMAN
    Dihydrofolate reductase 2, mitochon...
    DHFR2
    114Annotation score:

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_061135166V → I1 PublicationCorresponds to variant dbSNP:rs17855824Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL832912 mRNA Translation: CAH10617.1
    AC130896 Genomic DNA No translation available.
    CH471052 Genomic DNA Translation: EAW79895.1
    CH471052 Genomic DNA Translation: EAW79896.1
    BC045541 mRNA Translation: AAH45541.1
    BC063379 mRNA Translation: AAH63379.1
    CCDSiCCDS2926.1
    RefSeqiNP_001182572.1, NM_001195643.1
    NP_789785.1, NM_176815.4
    XP_011510839.1, XM_011512537.2
    UniGeneiHs.718516

    Genome annotation databases

    EnsembliENST00000314636; ENSP00000319170; ENSG00000178700
    ENST00000394221; ENSP00000377768; ENSG00000178700
    ENST00000461173; ENSP00000418415; ENSG00000178700
    ENST00000619045; ENSP00000480823; ENSG00000178700
    GeneIDi200895
    KEGGihsa:200895
    UCSCiuc003dri.3 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL832912 mRNA Translation: CAH10617.1
    AC130896 Genomic DNA No translation available.
    CH471052 Genomic DNA Translation: EAW79895.1
    CH471052 Genomic DNA Translation: EAW79896.1
    BC045541 mRNA Translation: AAH45541.1
    BC063379 mRNA Translation: AAH63379.1
    CCDSiCCDS2926.1
    RefSeqiNP_001182572.1, NM_001195643.1
    NP_789785.1, NM_176815.4
    XP_011510839.1, XM_011512537.2
    UniGeneiHs.718516

    3D structure databases

    ProteinModelPortaliQ86XF0
    SMRiQ86XF0
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi128354, 61 interactors
    IntActiQ86XF0, 2 interactors
    STRINGi9606.ENSP00000319170

    PTM databases

    iPTMnetiQ86XF0
    PhosphoSitePlusiQ86XF0

    Polymorphism and mutation databases

    BioMutaiDHFRL1
    DMDMi74727819

    Proteomic databases

    EPDiQ86XF0
    MaxQBiQ86XF0
    PaxDbiQ86XF0
    PeptideAtlasiQ86XF0
    PRIDEiQ86XF0
    ProteomicsDBi70273
    TopDownProteomicsiQ86XF0

    Protocols and materials databases

    DNASUi200895
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000314636; ENSP00000319170; ENSG00000178700
    ENST00000394221; ENSP00000377768; ENSG00000178700
    ENST00000461173; ENSP00000418415; ENSG00000178700
    ENST00000619045; ENSP00000480823; ENSG00000178700
    GeneIDi200895
    KEGGihsa:200895
    UCSCiuc003dri.3 human

    Organism-specific databases

    CTDi200895
    DisGeNETi200895
    EuPathDBiHostDB:ENSG00000178700.7
    GeneCardsiDHFR2
    HGNCiHGNC:27309 DHFR2
    HPAiHPA051465
    MIMi616588 gene
    neXtProtiNX_Q86XF0
    OpenTargetsiENSG00000178700
    PharmGKBiPA134889916
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1324 Eukaryota
    COG0262 LUCA
    GeneTreeiENSGT00390000010283
    HOGENOMiHOG000040235
    HOVERGENiHBG000773
    InParanoidiQ86XF0
    KOiK00287
    OMAiQYEFQMW
    OrthoDBiEOG091G0PRK
    PhylomeDBiQ86XF0
    TreeFamiTF317636

    Enzyme and pathway databases

    UniPathwayi
    UPA00077;UER00158

    BioCyciMetaCyc:ENSG00000178700-MONOMER
    ReactomeiR-HSA-196757 Metabolism of folate and pterines

    Miscellaneous databases

    ChiTaRSiDHFR2 human
    GenomeRNAii200895
    PROiPR:Q86XF0
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000178700 Expressed in 208 organ(s), highest expression level in buccal mucosa cell
    ExpressionAtlasiQ86XF0 baseline and differential
    GenevisibleiQ86XF0 HS

    Family and domain databases

    CDDicd00209 DHFR, 1 hit
    Gene3Di3.40.430.10, 1 hit
    InterProiView protein in InterPro
    IPR024072 DHFR-like_dom_sf
    IPR001796 DHFR_dom
    PfamiView protein in Pfam
    PF00186 DHFR_1, 1 hit
    SUPFAMiSSF53597 SSF53597, 1 hit
    PROSITEiView protein in PROSITE
    PS51330 DHFR_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiDYR2_HUMAN
    AccessioniPrimary (citable) accession number: Q86XF0
    Secondary accession number(s): D3DN30, Q6P4I9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 20, 2005
    Last sequence update: June 1, 2003
    Last modified: November 7, 2018
    This is version 123 of the entry and version 1 of the sequence. See 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

    Complete proteome, Reference proteome

    Documents

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

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