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Protein

Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial

Gene

DUT

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

Functioni

This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.1 Publication

Miscellaneous

Each trimer binds three substrate molecules. The ligands are bound between subunits, and for each substrate molecule, residues from adjacent subunits contribute to the binding interactions.

Catalytic activityi

dUTP + H2O = dUMP + diphosphate.1 Publication

Cofactori

Mg2+1 Publication

Enzyme regulationi

Phosphorylation is necessary for activity.

Kineticsi

for both isoform 2 and isoform 3.
  1. KM=2.5 µM for dUTP1 Publication

    Pathwayi: dUMP biosynthesis

    This protein is involved in step 2 of the subpathway that synthesizes dUMP from dCTP (dUTP route).
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. no protein annotated in this organism
    2. Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (DUT)
    This subpathway is part of the pathway dUMP biosynthesis, which is itself part of Pyrimidine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes dUMP from dCTP (dUTP route), the pathway dUMP biosynthesis and in Pyrimidine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei198Substrate; via amide nitrogen and carbonyl oxygen1 Publication1
    Binding sitei241SubstrateBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    • DNA replication Source: ProtInc
    • dUMP biosynthetic process Source: GO_Central
    • dUTP catabolic process Source: GO_Central
    • nucleobase-containing compound metabolic process Source: ProtInc
    • nucleobase-containing small molecule interconversion Source: Reactome

    Keywordsi

    Molecular functionHydrolase
    Biological processNucleotide metabolism
    LigandMagnesium

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05235-MONOMER
    BRENDAi3.6.1.23 2681
    ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates
    SABIO-RKiP33316
    UniPathwayiUPA00610; UER00666

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (EC:3.6.1.23)
    Short name:
    dUTPase
    Alternative name(s):
    dUTP pyrophosphatase
    Gene namesi
    Name:DUT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000128951.13
    HGNCiHGNC:3078 DUT
    MIMi601266 gene
    neXtProtiNX_P33316

    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

    Mitochondrion, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi99S → A: Loss of phosphorylation. 1 Publication1

    Organism-specific databases

    DisGeNETi1854
    OpenTargetsiENSG00000128951
    PharmGKBiPA151

    Chemistry databases

    ChEMBLiCHEMBL5203
    DrugBankiDB03413 Deoxyuridine-5'-Diphosphate

    Polymorphism and mutation databases

    BioMutaiDUT
    DMDMi347595814

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transit peptidei1 – 69MitochondrionCombined sources2 PublicationsAdd BLAST69
    ChainiPRO_000000739270 – 252Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrialAdd BLAST183
    Isoform 2 (identifier: P33316-2)
    Initiator methionineiRemovedCombined sources2 Publications

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei88PhosphoserineCombined sources1
    Modified residuei99PhosphoserineCombined sources1
    Isoform 2 (identifier: P33316-2)
    Modified residuei11PhosphoserineCombined sources2 Publications1

    Post-translational modificationi

    Nuclear isoform 2 is phosphorylated in vivo on Ser-11, a reaction that can be catalyzed in vitro by CDC2. Phosphorylation in mature T-cells occurs in a cell cycle-dependent manner. Isoform 3 is not phosphorylated.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiP33316
    PaxDbiP33316
    PeptideAtlasiP33316
    PRIDEiP33316
    TopDownProteomicsiP33316-2 [P33316-2]
    P33316-3 [P33316-3]

    PTM databases

    iPTMnetiP33316
    PhosphoSitePlusiP33316
    SwissPalmiP33316

    Expressioni

    Tissue specificityi

    Found in a variety of tissues. Isoform 3 expression is constitutive, while isoform 2 expression correlates with the onset of DNA replication (at protein level). Isoform 2 degradation coincides with the cessation of nuclear DNA replication (at protein level).1 Publication

    Gene expression databases

    BgeeiENSG00000128951
    CleanExiHS_DUT
    ExpressionAtlasiP33316 baseline and differential
    GenevisibleiP33316 HS

    Organism-specific databases

    HPAiHPA054422
    HPA060360

    Interactioni

    Subunit structurei

    Homotrimer.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    NUDT18Q6ZVK83EBI-353224,EBI-740486

    Protein-protein interaction databases

    BioGridi108187, 73 interactors
    IntActiP33316, 26 interactors
    STRINGi9606.ENSP00000370376

    Chemistry databases

    BindingDBiP33316

    Structurei

    Secondary structure

    1252
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi113 – 120Combined sources8
    Beta strandi127 – 130Combined sources4
    Beta strandi134 – 139Combined sources6
    Beta strandi144 – 146Combined sources3
    Beta strandi150 – 155Combined sources6
    Beta strandi158 – 161Combined sources4
    Beta strandi166 – 171Combined sources6
    Helixi174 – 180Combined sources7
    Beta strandi182 – 185Combined sources4
    Beta strandi198 – 203Combined sources6
    Beta strandi205 – 207Combined sources3
    Beta strandi209 – 211Combined sources3
    Beta strandi216 – 226Combined sources11
    Beta strandi229 – 232Combined sources4
    Beta strandi240 – 242Combined sources3
    Turni246 – 249Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1Q5HX-ray2.00A/B/C112-252[»]
    1Q5UX-ray2.00X/Y/Z112-252[»]
    2HQUX-ray2.20A/B/C94-252[»]
    3ARAX-ray1.70A/B/C94-252[»]
    3ARNX-ray1.80A/B/C94-252[»]
    3EHWX-ray1.80A/B/C/X/Y/Z94-252[»]
    4MZ5X-ray2.10A/C97-109[»]
    4MZ6X-ray1.88A/C97-109[»]
    5H4JX-ray1.80A94-252[»]
    ProteinModelPortaliP33316
    SMRiP33316
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP33316

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni173 – 175Substrate binding3
    Regioni187 – 190Substrate binding4
    Regioni246 – 247Substrate binding2

    Sequence similaritiesi

    Belongs to the dUTPase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiKOG3370 Eukaryota
    COG0756 LUCA
    GeneTreeiENSGT00390000018390
    KOiK01520
    OrthoDBiEOG091G14FN
    PhylomeDBiP33316
    TreeFamiTF105416

    Family and domain databases

    CDDicd07557 trimeric_dUTPase, 1 hit
    Gene3Di2.70.40.10, 1 hit
    InterProiView protein in InterPro
    IPR029054 dUTPase-like
    IPR036157 dUTPase-like_sf
    IPR008181 dUTPase_1
    IPR033704 dUTPase_trimeric
    PfamiView protein in Pfam
    PF00692 dUTPase, 1 hit
    SUPFAMiSSF51283 SSF51283, 1 hit
    TIGRFAMsiTIGR00576 dut, 1 hit

    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 3 (identifier: P33316-3) [UniParc]FASTAAdd to basket
    Also known as: DUT-M

    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
    MTPLCPRPAL CYHFLTSLLR SAMQNARGAR QRAEAAVLSG PGPPLGRAAQ
    60 70 80 90 100
    HGIPRPLSSA GRLSQGCRGA STVGAAGWKG ELPKAGGSPA PGPETPAISP
    110 120 130 140 150
    SKRARPAEVG GMQLRFARLS EHATAPTRGS ARAAGYDLYS AYDYTIPPME
    160 170 180 190 200
    KAVVKTDIQI ALPSGCYGRV APRSGLAAKH FIDVGAGVID EDYRGNVGVV
    210 220 230 240 250
    LFNFGKEKFE VKKGDRIAQL ICERIFYPEI EEVQALDDTE RGSGGFGSTG

    KN
    Length:252
    Mass (Da):26,563
    Last modified:September 21, 2011 - v4
    Checksum:i8E2EBC9ED5B0FAD2
    GO
    Isoform 2 (identifier: P33316-2) [UniParc]FASTAAdd to basket
    Also known as: DUT-N

    The sequence of this isoform differs from the canonical sequence as follows:
         1-93: MTPLCPRPAL...KAGGSPAPGP → MPCSE

    Note: Major isoform.Combined sources2 Publications
    Show »
    Length:164
    Mass (Da):17,748
    Checksum:iE75BC583BF8C7245
    GO

    Sequence cautioni

    The sequence AAB71393 differs from that shown. Reason: Frameshift at positions 29 and 47.Curated
    The sequence AAB93866 differs from that shown. Reason: Frameshift at positions 29 and 47.Curated
    The sequence AAB94642 differs from that shown. Reason: Frameshift at positions 29 and 47.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti175G → S in BAF84204 (PubMed:14702039).Curated1
    Sequence conflicti182I → T in BAG60677 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_022314100P → S1 PublicationCorresponds to variant dbSNP:rs28381104Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0013241 – 93MTPLC…PAPGP → MPCSE in isoform 2. 6 PublicationsAdd BLAST93

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U31930 mRNA Translation: AAC50418.1
    U62891 mRNA Translation: AAC51123.1
    AF018432
    , AF018429, AF018430, AF018431 Genomic DNA Translation: AAB71393.1 Frameshift.
    AF018432
    , AF018429, AF018430, AF018431 Genomic DNA Translation: AAB71394.1
    U90223 mRNA Translation: AAB94642.1 Frameshift.
    U90224 Genomic DNA Translation: AAB93866.1 Frameshift.
    U90224 Genomic DNA Translation: AAB93867.1
    AB049113 mRNA Translation: BAB13724.1
    AY935242 Genomic DNA Translation: AAX14045.1
    AK291515 mRNA Translation: BAF84204.1
    AK312122 mRNA Translation: BAG35058.1
    CR541720 mRNA Translation: CAG46521.1
    CR541781 mRNA Translation: CAG46580.1
    CH471082 Genomic DNA Translation: EAW77350.1
    AK298464 mRNA Translation: BAG60677.1
    BC033645 mRNA Translation: AAH33645.1
    BC070339 mRNA Translation: AAH70339.1
    BC110377 mRNA Translation: AAI10378.1
    M89913 mRNA Translation: AAA58444.1
    L11877 mRNA Translation: AAA36801.1
    CCDSiCCDS32231.1 [P33316-3]
    CCDS45255.1 [P33316-2]
    PIRiA46256
    G02777
    RefSeqiNP_001020419.1, NM_001025248.1 [P33316-3]
    NP_001020420.1, NM_001025249.1
    NP_001317215.1, NM_001330286.1
    NP_001939.1, NM_001948.3 [P33316-2]
    UniGeneiHs.527980

    Genome annotation databases

    EnsembliENST00000331200; ENSP00000370376; ENSG00000128951 [P33316-3]
    ENST00000455976; ENSP00000405160; ENSG00000128951 [P33316-2]
    GeneIDi1854
    KEGGihsa:1854
    UCSCiuc001zws.4 human [P33316-3]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiDUT_HUMAN
    AccessioniPrimary (citable) accession number: P33316
    Secondary accession number(s): A8K650
    , B4DPR5, O14785, Q16708, Q16860, Q6FHN1, Q6NSA3, Q96Q81
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: September 21, 2011
    Last modified: May 23, 2018
    This is version 193 of the entry and version 4 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

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: 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

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