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DUT deoxyuridine triphosphatase [ Homo sapiens (human) ]

Gene ID: 1854, updated on 12-Nov-2024

Summary

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Official Symbol
DUTprovided by HGNC
Official Full Name
deoxyuridine triphosphataseprovided by HGNC
Primary source
HGNC:HGNC:3078
See related
Ensembl:ENSG00000128951 MIM:601266; AllianceGenome:HGNC:3078
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
BMFDMS; dUTPase
Summary
This gene encodes an essential enzyme of nucleotide metabolism. The encoded protein forms a ubiquitous, homotetrameric enzyme that hydrolyzes dUTP to dUMP and pyrophosphate. This reaction serves two cellular purposes: providing a precursor (dUMP) for the synthesis of thymine nucleotides needed for DNA replication, and limiting intracellular pools of dUTP. Elevated levels of dUTP lead to increased incorporation of uracil into DNA, which induces extensive excision repair mediated by uracil glycosylase. This repair process, resulting in the removal and reincorporation of dUTP, is self-defeating and leads to DNA fragmentation and cell death. Alternative splicing of this gene leads to different isoforms that localize to either the mitochondrion or nucleus. A related pseudogene is located on chromosome 19. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 16.5), lymph node (RPKM 14.4) and 25 other tissues See more
Orthologs
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Genomic context

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See DUT in Genome Data Viewer
Location:
15q21.1
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (48331095..48343373)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (46139356..46151634)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (48623292..48635570)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC128966560 Neighboring gene solute carrier family 12 member 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:48543423-48544622 Neighboring gene MPRA-validated peak2328 silencer Neighboring gene uncharacterized LOC124903486 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:48621665-48621855 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:48623134-48623660 Neighboring gene Sharpr-MPRA regulatory region 3998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6416 Neighboring gene DUT antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:48707937-48708437 Neighboring gene fibrillin 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:48764566-48765765 Neighboring gene Sharpr-MPRA regulatory region 3576 Neighboring gene Sharpr-MPRA regulatory region 9539 Neighboring gene uncharacterized LOC124903488 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:48821930-48823129 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9375 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6417 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6418 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6419 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6420 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:48937944-48938468 Neighboring gene FBN1 divergent transcript

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Structural model of human dUTPase in complex with a novel proteinaceous inhibitor. Nyíri K, et al. Sci Rep, 2018 Mar 12. PMID 29531348, Free PMC Article
  2. Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability. Szabó JE, et al. Sci Rep, 2021 Sep 28. PMID 34584184, Free PMC Article
  3. Homotrimeric dUTPases; structural solutions for specific recognition and hydrolysis of dUTP. Persson R, et al. Curr Protein Pept Sci, 2001 Dec. PMID 12369926
  4. The role of dUTPase and uracil-DNA repair in cancer chemotherapy. Ladner RD. Curr Protein Pept Sci, 2001 Dec. PMID 12374095
  5. Identification of sequence determinants of human nuclear dUTPase isoform localization. Tinkelenberg BA, et al. Exp Cell Res, 2003 Jul 1. PMID 12799180

See all (96) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Structural dynamics of human deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase).
    Title: Structural dynamics of human deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase).
  2. Discovery of two new isoforms of the human DUT gene.
    Title: Discovery of two new isoforms of the human DUT gene.
  3. DUT enhances drug resistance to proteasome inhibitors via promoting mitochondrial function in multiple myeloma.
    Title: DUT enhances drug resistance to proteasome inhibitors via promoting mitochondrial function in multiple myeloma.
  4. Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability.
    Title: Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability.
  5. These findings suggested that the homozygous GG allele of rs3784619 and the TT allele of rs11637235 in the DUT gene significantly increased the risk of cervical intraepithelial neoplasia III and cervical squamous cell carcinomas.
    Title: Genetic variants of the dUTPase-encoding gene DUT increase HR-HPV infection rate and cervical squamous cell carcinoma risk.
  6. This study reports that the Staphylococcal repressor protein StlSaPIBov1 (Stl) forms strong complex with human dUTPase.
    Title: Structural model of human dUTPase in complex with a novel proteinaceous inhibitor.
  7. A single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene was associated with a syndrome of bone marrow failure and diabetes.
    Title: dUTPase (DUT) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure.
  8. Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus.
    Title: Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: structural and mechanistic insights.
  9. EBV-encoded dUTPase may act as an intercellular signaling molecule capable of modulating the cellular microenvironment
    Title: Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells.
  10. Data sugget that inhibition of dUTPase is a mechanism-based therapeutic approach to significantly enhance the efficacy of thymidylate synthase (TS)-targeted chemotherapeutic agents.
    Title: Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer.
Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Bone marrow failure and diabetes mellitus syndrome
MedGen: C5774218 OMIM: 620044 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
A genome-wide association study identifies protein quantitative trait loci (pQTLs).
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
retropepsin gag-pol Positional proteomics analysis identifies the cleavage of human deoxyuridine triphosphatase (DUT) at amino acid residues 231-232 by the HIV-1 protease PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ20622

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables dUTP diphosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables dUTP diphosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables magnesium ion binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA replication TAS
Traceable Author Statement
more info
 PubMed 
involved_in dTMP biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in dUMP biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in dUMP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in dUTP catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nucleobase-containing compound metabolic process TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in extracellular exosome HDA PubMed 
located_in mitochondrion HTP PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial
Names
dUTP diphosphatase
dUTP nucleotidohydrolase
dUTP pyrophosphatase
NP_001020419.1
NP_001020420.1
NP_001317215.1
NP_001939.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029497.1 RefSeqGene

    Range
    5006..16950
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001025248.2 → NP_001020419.1  deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_001020419.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), also known as DUT-M, represents the longest transcript. It encodes the longest isoform (1), which includes a mitochondrial targeting sequence.
    Source sequence(s)
    AC023355, BC070339, BF697257, BI257870
    Consensus CDS
    CCDS32231.1
    UniProtKB/Swiss-Prot
    A8K650, B4DPR5, O14785, P33316, Q16708, Q16860, Q6FHN1, Q6NSA3, Q96Q81
    UniProtKB/TrEMBL
    H0YKC5
    Related
    ENSP00000370376.2, ENST00000331200.8
    Conserved Domains (2) summary
    PRK12727
    Location:17 → 163
    PRK12727; flagellar biosynthesis protein FlhF
    TIGR00576
    Location:114 → 251
    dut; deoxyuridine 5'-triphosphate nucleotidohydrolase (dut)

  2. NM_001025249.1 → NP_001020420.1  deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial isoform 3

    See identical proteins and their annotated locations for NP_001020420.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and uses a downstream start codon, compared to variant 1. It encodes isoform 3, which has a shorter N-terminus that lacks the mitochondrial targeting sequence, compared to isoform 1.
    Source sequence(s)
    AC023355, AK000629, BG505144, BI257870
    Consensus CDS
    CCDS45256.1
    UniProtKB/TrEMBL
    A0A0C4DGL3
    Related
    ENSP00000453717.1, ENST00000558813.5
    Conserved Domains (1) summary
    cl00493
    Location:3 → 139
    trimeric_dUTPase; Trimeric dUTP diphosphatases

  3. NM_001330286.2 → NP_001317215.1  deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate start codon, compared to variant 1. It encodes isoform 4, which has a shorter, distinct N-terminus that lacks the mitochondrial targeting sequence, compared to isoform 1.
    Source sequence(s)
    AB049113, AC023355, BP208983
    Consensus CDS
    CCDS81879.1
    UniProtKB/TrEMBL
    H0YNW5
    Related
    ENSP00000454183.1, ENST00000559416.5
    Conserved Domains (1) summary
    cl00493
    Location:29 → 165
    trimeric_dUTPase; Trimeric dUTP diphosphatases

  4. NM_001948.4 → NP_001939.1  deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial isoform 2

    See identical proteins and their annotated locations for NP_001939.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as DUT-N, uses a different 5' exon, compared to variant 1. It encodes isoform 2, which has a shorter, distinct N-terminus that lacks the mitochondrial targeting sequence, compared to isoform 1.
    Source sequence(s)
    AB049113, AC023355, BG532018, BI257870
    Consensus CDS
    CCDS45255.1
    UniProtKB/Swiss-Prot
    P33316
    Related
    ENSP00000405160.2, ENST00000455976.6
    Conserved Domains (1) summary
    cl00493
    Location:26 → 162
    trimeric_dUTPase; Trimeric dUTP diphosphatases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    48331095..48343373
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    46139356..46151634
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P33316.4 GenPept UniProtKB/Swiss-Prot:P33316

Gene LinkOut

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