DUT

Protein identityUniProt · HPA

UniProt accession

P33316

Gene

DUT

Ensembl

ENSG00000128951

Chromosome

15

Canonical length

252 aa

Protein class

Enzymes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

Quaternary structure

Homotrimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

252 residues, UniProt reviewed canonical sequence.

>P33316|DUT
     1  MTPLCPRPAL CYHFLTSLLR SAMQNARGAR QRAEAAVLSG PGPPLGRAAQ HGIPRPLSSA
    61  GRLSQGCRGA STVGAAGWKG ELPKAGGSPA PGPETPAISP SKRARPAEVG GMQLRFARLS
   121  EHATAPTRGS ARAAGYDLYS AYDYTIPPME KAVVKTDIQI ALPSGCYGRV APRSGLAAKH
   181  FIDVGAGVID EDYRGNVGVV LFNFGKEKFE VKKGDRIAQL ICERIFYPEI EEVQALDDTE
   241  RGSGGFGSTG KN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DUT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.52

Highest tissue expression

154 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DUT.

Disease | AllUniProt

Conditions DUT is implicated in, by any mechanism.

• Bone marrow failure and diabetes mellitus syndrome (BMFDMS) MIM:620044

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 21 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Bone marrow failure and diabetes mellitus syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.12

gnomAD pLI

0

gnomAD missense Z

1.16

DepMap mean gene effect

-1.75

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA replication
• dTMP biosynthetic process
• dUMP biosynthetic process
• dUTP catabolic process
• liver development
• nucleobase-containing compound metabolic process
• regulation of protein-containing complex assembly

Molecular functions

• dUTP diphosphatase activity
• identical protein binding
• magnesium ion binding
• peroxisome proliferator activated receptor binding
• pyrimidine deoxyribonucleotide binding
• RNA binding
• signaling receptor inhibitor activity

Cellular components

• extracellular exosome
• mitochondrion
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• dUTPase-like
• dUTPase, trimeric
• dUTPase-like superfamily
• dUTPase
• Deoxyuridine triphosphate nucleotidohydrolase

KeywordsUniProt

• Diabetes mellitus
• Hydrolase
• Magnesium
• Mitochondrion
• Nucleotide metabolism
• Nucleus
• Phosphoprotein
• Transit peptide