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P04753

- DYR_MESAU

UniProt

P04753 - DYR_MESAU

Protein

Dihydrofolate reductase

Gene

DHFR

Organism
Mesocricetus auratus (Golden hamster)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 82 (01 Oct 2014)
      Sequence version 4 (23 Jan 2007)
      Previous versions | rss
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    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 By similarity.By similarity

    Catalytic activityi

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

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei10 – 101NADP; via amide nitrogen and carbonyl oxygenBy similarity
    Binding sitei71 – 711SubstrateBy similarity
    Binding sitei137 – 1371MethotrexateCurated

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi16 – 227NADPBy similarity
    Nucleotide bindingi55 – 573NADPBy similarity
    Nucleotide bindingi77 – 793NADPBy similarity
    Nucleotide bindingi117 – 1248NADPBy similarity

    GO - Molecular functioni

    1. dihydrofolate reductase activity Source: UniProtKB
    2. drug binding Source: UniProtKB
    3. mRNA binding Source: UniProtKB
    4. NADP binding Source: InterPro

    GO - Biological processi

    1. glycine biosynthetic process Source: InterPro
    2. nucleotide biosynthetic process Source: InterPro
    3. one-carbon metabolic process Source: UniProtKB-KW
    4. response to methotrexate Source: UniProtKB-KW
    5. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
    6. tetrahydrofolate metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Methotrexate resistance, One-carbon metabolism

    Keywords - Ligandi

    NADP, RNA-binding

    Enzyme and pathway databases

    UniPathwayiUPA00077; UER00158.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dihydrofolate reductase (EC:1.5.1.3)
    Gene namesi
    Name:DHFR
    OrganismiMesocricetus auratus (Golden hamster)
    Taxonomic identifieri10036 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeMesocricetus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 187186Dihydrofolate reductasePRO_0000186363Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei33 – 331N6-acetyllysine; alternateBy similarity
    Modified residuei33 – 331N6-succinyllysine; alternateBy similarity

    Keywords - PTMi

    Acetylation

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP04753.
    SMRiP04753. Positions 2-186.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 185182DHFRPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni8 – 3730Involved in methotrexate bindingCuratedAdd
    BLAST
    Regioni31 – 366Substrate bindingBy similarity
    Regioni60 – 7011Involved in methotrexate bindingCuratedAdd
    BLAST

    Sequence similaritiesi

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

    Phylogenomic databases

    HOVERGENiHBG000773.

    Family and domain databases

    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]

    Sequencei

    Sequence statusi: Complete.

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

    P04753-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVRPLNCIVA VSQNMGIGKN GDFPWPMLRN EFKYFQRMTT TSSVEGKQNL    50
    VIMGRKTWFS IPEKNRPLKD RINIVLSREL KEPPQGAHFL AKSLDDALKL 100
    IEQPELADKV DMVWIVGGSS VYKEAMNQPG HLRLFVTRIM QEFESDTFFP 150
    EIDLEKYKLL PEYPGVLSEV QEEKGIKYKF EVYEKKG 187
    Length:187
    Mass (Da):21,660
    Last modified:January 23, 2007 - v4
    Checksum:iA91F85A74658C6F3
    GO

    Polymorphismi

    The sequence shown is that of A3-35. The two clones A3-35 and MQ19-97 represent allelic forms. They differ in their drug sensitivities, possibly because of the difference at position 22.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti23 – 231F → L in MQ19-97.
    Natural varianti96 – 961D → N in MQ19-97.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01164 mRNA. Translation: AAA36974.1.
    K01165 mRNA. Translation: AAA36976.1.
    M19869 mRNA. Translation: AAA36970.1.
    PIRiS42445.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01164 mRNA. Translation: AAA36974.1 .
    K01165 mRNA. Translation: AAA36976.1 .
    M19869 mRNA. Translation: AAA36970.1 .
    PIRi S42445.

    3D structure databases

    ProteinModelPortali P04753.
    SMRi P04753. Positions 2-186.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    HOVERGENi HBG000773.

    Enzyme and pathway databases

    UniPathwayi UPA00077 ; UER00158 .

    Family and domain databases

    Gene3Di 3.40.430.10. 1 hit.
    InterProi IPR012259. DHFR.
    IPR024072. DHFR-like_dom.
    IPR017925. DHFR_CS.
    IPR001796. DHFR_dom.
    [Graphical view ]
    Pfami PF00186. DHFR_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00070. DHFR.
    SUPFAMi SSF53597. SSF53597. 1 hit.
    PROSITEi PS00075. DHFR_1. 1 hit.
    PS51330. DHFR_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Antifolate-resistant Chinese hamster cells. Molecular basis for the biochemical and structural heterogeneity among dihydrofolate reductases produced by drug-sensitive and drug-resistant cell lines."
      Melera P.W., Davide J.P., Oen H.
      J. Biol. Chem. 263:1978-1990(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Phenotypic expression in Escherichia coli and nucleotide sequence of two Chinese hamster lung cell cDNAs encoding different dihydrofolate reductases."
      Melera P.W., Davide J.P., Hession C.A., Scotto K.W.
      Mol. Cell. Biol. 4:38-48(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Lung fibroblast.
    3. Erratum
      Melera P.W., Davide J.P., Hession C.A., Scotto K.W.
      Mol. Cell. Biol. 4:1001-1001(1984)

    Entry informationi

    Entry nameiDYR_MESAU
    AccessioniPrimary (citable) accession number: P04753
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 82 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Overexpression of the dihydrofolate gene (generally involving gene amplification) results in resistance to the antitumor antifolate drugs methotrexate (MTX) and methasquin.
    Cell line DC-3F/A3 produces 90% of its dihydrofolate reductase in the 21k pI 6.5 form.
    Cell line DC-3F/MQ19 produces 90% of its dihydrofolate reductase in the 20k pI 6.7 form (DHFR97).

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3