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Protein

Dihydrofolate reductase, mitochondrial

Gene

DHFRL1

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. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.2 Publications

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

    Pathway:itetrahydrofolate 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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei10 – 101NADP; via amide nitrogen and carbonyl oxygenBy similarity
    Binding sitei71 – 711SubstrateBy similarity

    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

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

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    One-carbon metabolism

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    ReactomeiREACT_11167. Metabolism of folate and pterines.
    UniPathwayiUPA00077; UER00158.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dihydrofolate reductase, mitochondrial (EC:1.5.1.3)
    Alternative name(s):
    Dihydrofolate reductase-like protein 1
    Gene namesi
    Name:DHFRL1
    Synonyms:DHFRP4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:27309. DHFRL1.

    Subcellular locationi

    GO - Cellular componenti

    • mitochondrial inner membrane Source: UniProtKB
    • mitochondrial matrix Source: UniProtKB
    • mitochondrion Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Mitochondrion inner membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134889916.

    Polymorphism and mutation databases

    BioMutaiDHFRL1.
    DMDMi74727819.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 187187Dihydrofolate reductase, mitochondrialPRO_0000186368Add
    BLAST

    Proteomic databases

    PaxDbiQ86XF0.
    PRIDEiQ86XF0.

    PTM databases

    PhosphoSiteiQ86XF0.

    Expressioni

    Tissue specificityi

    Expressed in numerous cell lines.1 Publication

    Gene expression databases

    BgeeiQ86XF0.
    ExpressionAtlasiQ86XF0. baseline and differential.
    GenevisibleiQ86XF0. HS.

    Organism-specific databases

    HPAiHPA051465.

    Interactioni

    Protein-protein interaction databases

    BioGridi128354. 11 interactions.
    IntActiQ86XF0. 1 interaction.
    STRINGi9606.ENSP00000319170.

    Structurei

    3D structure databases

    ProteinModelPortaliQ86XF0.
    SMRiQ86XF0. Positions 5-186.
    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
    Regioni31 – 366Substrate bindingBy similarity

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG0262.
    GeneTreeiENSGT00390000010283.
    HOGENOMiHOG000040235.
    HOVERGENiHBG000773.
    InParanoidiQ86XF0.
    KOiK00287.
    OMAiIYLTHID.
    OrthoDBiEOG7V1FS3.
    PhylomeDBiQ86XF0.
    TreeFamiTF317636.

    Family and domain databases

    Gene3Di3.40.430.10. 1 hit.
    InterProiIPR012259. DHFR.
    IPR024072. DHFR-like_dom.
    IPR001796. DHFR_dom.
    [Graphical view]
    PfamiPF00186. DHFR_1. 1 hit.
    [Graphical view]
    PRINTSiPR00070. DHFR.
    SUPFAMiSSF53597. SSF53597. 1 hit.
    PROSITEiPS51330. DHFR_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti166 – 1661V → I.1 Publication
    Corresponds to variant rs17855824 [ dbSNP | Ensembl ].
    VAR_061135

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL832912 mRNA. Translation: CAH10617.1.
    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_011512537.1.
    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

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL832912 mRNA. Translation: CAH10617.1.
    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_011512537.1.
    UniGeneiHs.718516.

    3D structure databases

    ProteinModelPortaliQ86XF0.
    SMRiQ86XF0. Positions 5-186.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi128354. 11 interactions.
    IntActiQ86XF0. 1 interaction.
    STRINGi9606.ENSP00000319170.

    PTM databases

    PhosphoSiteiQ86XF0.

    Polymorphism and mutation databases

    BioMutaiDHFRL1.
    DMDMi74727819.

    Proteomic databases

    PaxDbiQ86XF0.
    PRIDEiQ86XF0.

    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.
    GeneCardsiGC03M093766.
    HGNCiHGNC:27309. DHFRL1.
    HPAiHPA051465.
    neXtProtiNX_Q86XF0.
    PharmGKBiPA134889916.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0262.
    GeneTreeiENSGT00390000010283.
    HOGENOMiHOG000040235.
    HOVERGENiHBG000773.
    InParanoidiQ86XF0.
    KOiK00287.
    OMAiIYLTHID.
    OrthoDBiEOG7V1FS3.
    PhylomeDBiQ86XF0.
    TreeFamiTF317636.

    Enzyme and pathway databases

    UniPathwayiUPA00077; UER00158.
    ReactomeiREACT_11167. Metabolism of folate and pterines.

    Miscellaneous databases

    ChiTaRSiDHFRL1. human.
    GenomeRNAii200895.
    NextBioi90000.
    PROiQ86XF0.

    Gene expression databases

    BgeeiQ86XF0.
    ExpressionAtlasiQ86XF0. baseline and differential.
    GenevisibleiQ86XF0. HS.

    Family and domain databases

    Gene3Di3.40.430.10. 1 hit.
    InterProiIPR012259. DHFR.
    IPR024072. DHFR-like_dom.
    IPR001796. DHFR_dom.
    [Graphical view]
    PfamiPF00186. DHFR_1. 1 hit.
    [Graphical view]
    PRINTSiPR00070. DHFR.
    SUPFAMiSSF53597. SSF53597. 1 hit.
    PROSITEiPS51330. DHFR_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Melanoma.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-166.
      Tissue: Brain and Muscle.
    4. "Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria."
      Anderson D.D., Quintero C.M., Stover P.J.
      Proc. Natl. Acad. Sci. U.S.A. 108:15163-15168(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    5. "The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional."
      McEntee G., Minguzzi S., O'Brien K., Ben Larbi N., Loscher C., O'Fagain C., Parle-McDermott A.
      Proc. Natl. Acad. Sci. U.S.A. 108:15157-15162(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, RNA-BINDING, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiDYRL1_HUMAN
    AccessioniPrimary (citable) accession number: Q86XF0
    Secondary accession number(s): D3DN30, Q6P4I9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 20, 2005
    Last sequence update: June 1, 2003
    Last modified: July 22, 2015
    This is version 99 of the entry and version 1 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.