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Protein

Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial

Gene

DUT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

    • dUTP diphosphatase activity Source: Reactome
    • magnesium ion binding Source: GO_Central
    • poly(A) RNA binding Source: UniProtKB

    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
    • pyrimidine nucleoside biosynthetic process Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Nucleotide metabolism

    Keywords - Ligandi

    Magnesium

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05235-MONOMER.
    ZFISH:HS05235-MONOMER.
    BRENDAi3.6.1.23. 2681.
    ReactomeiR-HSA-500753. Pyrimidine biosynthesis.
    SABIO-RKP33316.
    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

    HGNCiHGNC:3078. DUT.

    Subcellular locationi

    Isoform 2 :
    Isoform 3 :

    GO - Cellular componenti

    • extracellular exosome Source: UniProtKB
    • mitochondrion Source: ProtInc
    • nucleoplasm Source: HPA
    • nucleus Source: ProtInc
    Complete GO annotation...

    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.

    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. 71 interactors.
    IntActiP33316. 21 interactors.
    MINTiMINT-1436411.
    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[»]
    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.
    InterProiIPR029054. dUTPase-like.
    IPR008180. dUTPase/dCTP_deaminase.
    IPR008181. dUTPase_1.
    IPR033704. dUTPase_trimeric.
    [Graphical view]
    PfamiPF00692. dUTPase. 1 hit.
    [Graphical view]
    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 → S.1 PublicationCorresponds to variant rs28381104dbSNPEnsembl.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

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    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.

    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[»]
    ProteinModelPortaliP33316.
    SMRiP33316.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108187. 71 interactors.
    IntActiP33316. 21 interactors.
    MINTiMINT-1436411.
    STRINGi9606.ENSP00000370376.

    Chemistry databases

    BindingDBiP33316.
    ChEMBLiCHEMBL5203.

    PTM databases

    iPTMnetiP33316.
    PhosphoSitePlusiP33316.
    SwissPalmiP33316.

    Polymorphism and mutation databases

    BioMutaiDUT.
    DMDMi347595814.

    Proteomic databases

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

    Protocols and materials databases

    DNASUi1854.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi1854.
    DisGeNETi1854.
    GeneCardsiDUT.
    HGNCiHGNC:3078. DUT.
    HPAiHPA054422.
    HPA060360.
    MIMi601266. gene.
    neXtProtiNX_P33316.
    OpenTargetsiENSG00000128951.
    PharmGKBiPA151.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3370. Eukaryota.
    COG0756. LUCA.
    GeneTreeiENSGT00390000018390.
    KOiK01520.
    OrthoDBiEOG091G14FN.
    PhylomeDBiP33316.
    TreeFamiTF105416.

    Enzyme and pathway databases

    UniPathwayiUPA00610; UER00666.
    BioCyciMetaCyc:HS05235-MONOMER.
    ZFISH:HS05235-MONOMER.
    BRENDAi3.6.1.23. 2681.
    ReactomeiR-HSA-500753. Pyrimidine biosynthesis.
    SABIO-RKP33316.

    Miscellaneous databases

    ChiTaRSiDUT. human.
    EvolutionaryTraceiP33316.
    GeneWikiiDUT_(gene).
    GenomeRNAii1854.
    PROiP33316.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000128951.
    CleanExiHS_DUT.
    ExpressionAtlasiP33316. baseline and differential.
    GenevisibleiP33316. HS.

    Family and domain databases

    CDDicd07557. trimeric_dUTPase. 1 hit.
    Gene3Di2.70.40.10. 1 hit.
    InterProiIPR029054. dUTPase-like.
    IPR008180. dUTPase/dCTP_deaminase.
    IPR008181. dUTPase_1.
    IPR033704. dUTPase_trimeric.
    [Graphical view]
    PfamiPF00692. dUTPase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51283. SSF51283. 1 hit.
    TIGRFAMsiTIGR00576. dut. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiDUT_HUMAN
    AccessioniPrimary (citable) accession number: P33316
    Secondary accession number(s): A8K650
    , B4DPR5, O14785, Q16708, Q16860, Q6FHN1, Q6NSA3, Q96Q81
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: September 21, 2011
    Last modified: November 30, 2016
    This is version 179 of the entry and version 4 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

    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.

    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

    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.