DUT deoxyuridine triphosphatase [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structural dynamics of human deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase).
Title: Structural dynamics of human deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase).
Discovery of two new isoforms of the human DUT gene.
Title: Discovery of two new isoforms of the human DUT gene.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

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

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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

RH122528 (e-PCR)
- UniSTS:138530

WI-17558 (e-PCR)
- UniSTS:39514

RH92298 (e-PCR)
- UniSTS:83814

M89913 (e-PCR)
- UniSTS:77682

RH39501 (e-PCR)
- UniSTS:92650

SHGC-36316 (e-PCR)
- UniSTS:61180

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	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 more info	PubMed
located_in mitochondrion	HTP more info	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

EC 3.6.1.23

NP_001020420.1

EC 3.6.1.23

NP_001317215.1

EC 3.6.1.23

NP_001939.1

EC 3.6.1.23

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

NG_029497.1 RefSeqGene

Range

5006..16950

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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)
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
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
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