UniProtKB - P33316 (DUT_HUMAN)
Protein
Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial
Gene
DUT
Organism
Homo sapiens (Human)
Status
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.3 Publications
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
- EC:3.6.1.233 Publications
Cofactori
Mg2+1 Publication
Activity regulationi
Phosphorylation is necessary for activity.
Kineticsi
kM is identical for both isoform 2 and isoform 3.1 Publication
- KM=2.5 µM for dUTP1 Publication
: dUMP biosynthesis Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes dUMP from dCTP (dUTP route).2 PublicationsProteins known to be involved in the 2 steps of the subpathway in this organism are:
- no protein annotated in this organism
- Deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT), Deoxyuridine 5'-triphosphate nucleotidohydrolase (FLJ00254), Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (DUT), Deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT), Deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT), Deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT), Deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT), Deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT), Deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 198 | dUTP; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1 Publication | 1 | |
Binding sitei | 241 | dUTPCombined sources1 Publication1 Publication | 1 |
GO - Molecular functioni
- dUTP diphosphatase activity Source: GO_Central
- magnesium ion binding Source: GO_Central
- 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
- nucleobase-containing small molecule interconversion Source: Reactome
Keywordsi
Molecular function | Hydrolase |
Biological process | Nucleotide metabolism |
Ligand | Magnesium |
Enzyme and pathway databases
BioCyci | MetaCyc:HS05235-MONOMER |
BRENDAi | 3.6.1.23, 2681 |
PathwayCommonsi | P33316 |
Reactomei | R-HSA-499943, Interconversion of nucleotide di- and triphosphates [P33316-2] |
SABIO-RKi | P33316 |
UniPathwayi | UPA00610;UER00666 |
Names & Taxonomyi
Protein namesi | Recommended name: Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial1 Publication (EC:3.6.1.233 Publications)Short name: dUTPase1 Publication Alternative name(s): dUTP pyrophosphatase |
Gene namesi | Name:DUT |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3078, DUT |
MIMi | 601266, gene |
neXtProti | NX_P33316 |
VEuPathDBi | HostDB:ENSG00000128951.13 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Mitochondrion
- Mitochondrion 2 Publications
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Mitochondrion
- mitochondrion Source: ProtInc
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: ProtInc
Keywords - Cellular componenti
Mitochondrion, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 99 | S → A: Loss of phosphorylation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 1854 |
OpenTargetsi | ENSG00000128951 |
PharmGKBi | PA151 |
Miscellaneous databases
Pharosi | P33316, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5203 |
DrugBanki | DB04685, 1-{(2S,5S)-4-FLUORO-5-[(TRITYLOXY)METHYL]TETRAHYDROFURAN-2-YL}PYRIMIDINE-2,4(1H,3H)-DIONE DB03413, Deoxyuridine-5'-Diphosphate |
Genetic variation databases
BioMutai | DUT |
DMDMi | 347595814 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Transit peptidei | 1 – 69 | MitochondrionCombined sources2 PublicationsAdd BLAST | 69 | ||
ChainiPRO_0000007392 | 70 – 252 | Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrialAdd BLAST | 183 | ||
Isoform 2 (identifier: P33316-2) | |||||
Initiator methioninei | Removed1 Publication |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Modified residuei | 88 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 99 | PhosphoserineCombined sources | 1 | ||
Isoform 2 (identifier: P33316-2) | |||||
Modified residuei | 11 | PhosphoserineCombined sources1 Publication | 1 |
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
PhosphoproteinProteomic databases
CPTACi | CPTAC-64 CPTAC-65 |
EPDi | P33316 |
jPOSTi | P33316 |
MassIVEi | P33316 |
PaxDbi | P33316 |
PeptideAtlasi | P33316 |
PRIDEi | P33316 |
ProteomicsDBi | 54908 [P33316-3] 54909 [P33316-2] |
TopDownProteomicsi | P33316-2 [P33316-2] P33316-3 [P33316-3] |
PTM databases
iPTMneti | P33316 |
MetOSitei | P33316 |
PhosphoSitePlusi | P33316 |
SwissPalmi | P33316 |
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
Bgeei | ENSG00000128951, Expressed in liver and 259 other tissues |
ExpressionAtlasi | P33316, baseline and differential |
Genevisiblei | P33316, HS |
Organism-specific databases
HPAi | ENSG00000128951, Low tissue specificity |
Interactioni
Subunit structurei
Homotrimer.
2 PublicationsBinary interactionsi
P33316
With | #Exp. | IntAct |
---|---|---|
NUDT18 [Q6ZVK8] | 3 | EBI-353224,EBI-740486 |
Protein-protein interaction databases
BioGRIDi | 108187, 96 interactors |
IntActi | P33316, 34 interactors |
STRINGi | 9606.ENSP00000370376 |
Chemistry databases
BindingDBi | P33316 |
Miscellaneous databases
RNActi | P33316, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P33316 |
SASBDBi | P33316 |
SMRi | P33316 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P33316 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 173 – 175 | dUTP bindingCombined sources1 Publication1 Publication | 3 | |
Regioni | 187 – 193 | dUTP bindingCombined sources1 Publication1 Publication | 7 | |
Regioni | 246 – 247 | dUTP bindingCombined sources1 Publication1 Publication | 2 |
Sequence similaritiesi
Belongs to the dUTPase family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG3370, Eukaryota |
GeneTreei | ENSGT00390000018390 |
OrthoDBi | 1495752at2759 |
PhylomeDBi | P33316 |
TreeFami | TF105416 |
Family and domain databases
CDDi | cd07557, trimeric_dUTPase, 1 hit |
Gene3Di | 2.70.40.10, 1 hit |
InterProi | View protein in InterPro IPR029054, dUTPase-like IPR036157, dUTPase-like_sf IPR008181, dUTPase_1 IPR033704, dUTPase_trimeric |
PANTHERi | PTHR11241, PTHR11241, 1 hit |
Pfami | View protein in Pfam PF00692, dUTPase, 1 hit |
SUPFAMi | SSF51283, SSF51283, 1 hit |
TIGRFAMsi | TIGR00576, dut, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All
Isoform 3 (identifier: P33316-3) [UniParc]FASTAAdd to basket
Also known as: DUT-M
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YNW5 | H0YNW5_HUMAN | Deoxyuridine 5'-triphosphate nucleo... | DUT | 167 | Annotation score: | ||
H0YKC5 | H0YKC5_HUMAN | Deoxyuridine 5'-triphosphate nucleo... | DUT | 221 | Annotation score: | ||
A0A0C4DGL3 | A0A0C4DGL3_HUMAN | Deoxyuridine 5'-triphosphate nucleo... | DUT hCG_41784 | 141 | Annotation score: | ||
H0YMP1 | H0YMP1_HUMAN | Deoxyuridine 5'-triphosphate nucleo... | DUT | 107 | Annotation score: | ||
H0YMM5 | H0YMM5_HUMAN | Deoxyuridine 5'-triphosphate nucleo... | DUT | 133 | Annotation score: | ||
H0YKI0 | H0YKI0_HUMAN | Deoxyuridine 5'-triphosphate nucleo... | DUT | 226 | Annotation score: | ||
H0YNJ9 | H0YNJ9_HUMAN | Deoxyuridine 5'-triphosphate nucleo... | DUT | 143 | Annotation score: |
Sequence cautioni
The sequence AAB71393 differs from that shown. Reason: Frameshift.Curated
The sequence AAB93866 differs from that shown. Reason: Frameshift.Curated
The sequence AAB94642 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 175 | G → S in BAF84204 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 182 | I → T in BAG60677 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_022314 | 100 | P → S1 PublicationCorresponds to variant dbSNP:rs28381104EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_001324 | 1 – 93 | MTPLC…PAPGP → MPCSE in isoform 2. 6 PublicationsAdd BLAST | 93 |
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 |
CCDSi | CCDS32231.1 [P33316-3] CCDS45255.1 [P33316-2] |
PIRi | A46256 G02777 |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000331200; ENSP00000370376; ENSG00000128951 [P33316-3] ENST00000455976; ENSP00000405160; ENSG00000128951 [P33316-2] |
GeneIDi | 1854 |
KEGGi | hsa:1854 |
UCSCi | uc001zws.4, human [P33316-3] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS32231.1 [P33316-3] CCDS45255.1 [P33316-2] |
PIRi | A46256 G02777 |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1Q5H | X-ray | 2.00 | A/B/C | 112-252 | [»] | |
1Q5U | X-ray | 2.00 | X/Y/Z | 112-252 | [»] | |
2HQU | X-ray | 2.20 | A/B/C | 94-252 | [»] | |
3ARA | X-ray | 1.70 | A/B/C | 94-252 | [»] | |
3ARN | X-ray | 1.80 | A/B/C | 94-252 | [»] | |
3EHW | X-ray | 1.80 | A/B/C/X/Y/Z | 94-252 | [»] | |
4MZ5 | X-ray | 2.10 | A/C | 97-109 | [»] | |
4MZ6 | X-ray | 1.88 | A/C | 97-109 | [»] | |
5H4J | X-ray | 1.80 | A | 94-252 | [»] | |
BMRBi | P33316 | |||||
SASBDBi | P33316 | |||||
SMRi | P33316 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108187, 96 interactors |
IntActi | P33316, 34 interactors |
STRINGi | 9606.ENSP00000370376 |
Chemistry databases
BindingDBi | P33316 |
ChEMBLi | CHEMBL5203 |
DrugBanki | DB04685, 1-{(2S,5S)-4-FLUORO-5-[(TRITYLOXY)METHYL]TETRAHYDROFURAN-2-YL}PYRIMIDINE-2,4(1H,3H)-DIONE DB03413, Deoxyuridine-5'-Diphosphate |
PTM databases
iPTMneti | P33316 |
MetOSitei | P33316 |
PhosphoSitePlusi | P33316 |
SwissPalmi | P33316 |
Genetic variation databases
BioMutai | DUT |
DMDMi | 347595814 |
Proteomic databases
CPTACi | CPTAC-64 CPTAC-65 |
EPDi | P33316 |
jPOSTi | P33316 |
MassIVEi | P33316 |
PaxDbi | P33316 |
PeptideAtlasi | P33316 |
PRIDEi | P33316 |
ProteomicsDBi | 54908 [P33316-3] 54909 [P33316-2] |
TopDownProteomicsi | P33316-2 [P33316-2] P33316-3 [P33316-3] |
Protocols and materials databases
Antibodypediai | 24524, 374 antibodies |
DNASUi | 1854 |
Genome annotation databases
Ensembli | ENST00000331200; ENSP00000370376; ENSG00000128951 [P33316-3] ENST00000455976; ENSP00000405160; ENSG00000128951 [P33316-2] |
GeneIDi | 1854 |
KEGGi | hsa:1854 |
UCSCi | uc001zws.4, human [P33316-3] |
Organism-specific databases
CTDi | 1854 |
DisGeNETi | 1854 |
GeneCardsi | DUT |
HGNCi | HGNC:3078, DUT |
HPAi | ENSG00000128951, Low tissue specificity |
MIMi | 601266, gene |
neXtProti | NX_P33316 |
OpenTargetsi | ENSG00000128951 |
PharmGKBi | PA151 |
VEuPathDBi | HostDB:ENSG00000128951.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3370, Eukaryota |
GeneTreei | ENSGT00390000018390 |
OrthoDBi | 1495752at2759 |
PhylomeDBi | P33316 |
TreeFami | TF105416 |
Enzyme and pathway databases
UniPathwayi | UPA00610;UER00666 |
BioCyci | MetaCyc:HS05235-MONOMER |
BRENDAi | 3.6.1.23, 2681 |
PathwayCommonsi | P33316 |
Reactomei | R-HSA-499943, Interconversion of nucleotide di- and triphosphates [P33316-2] |
SABIO-RKi | P33316 |
Miscellaneous databases
BioGRID-ORCSi | 1854, 751 hits in 892 CRISPR screens |
ChiTaRSi | DUT, human |
EvolutionaryTracei | P33316 |
GeneWikii | DUT_(gene) |
GenomeRNAii | 1854 |
Pharosi | P33316, Tchem |
PROi | PR:P33316 |
RNActi | P33316, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000128951, Expressed in liver and 259 other tissues |
ExpressionAtlasi | P33316, baseline and differential |
Genevisiblei | P33316, HS |
Family and domain databases
CDDi | cd07557, trimeric_dUTPase, 1 hit |
Gene3Di | 2.70.40.10, 1 hit |
InterProi | View protein in InterPro IPR029054, dUTPase-like IPR036157, dUTPase-like_sf IPR008181, dUTPase_1 IPR033704, dUTPase_trimeric |
PANTHERi | PTHR11241, PTHR11241, 1 hit |
Pfami | View protein in Pfam PF00692, dUTPase, 1 hit |
SUPFAMi | SSF51283, SSF51283, 1 hit |
TIGRFAMsi | TIGR00576, dut, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DUT_HUMAN | |
Accessioni | P33316Primary (citable) accession number: P33316 Secondary accession number(s): A8K650 Q96Q81 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1994 |
Last sequence update: | September 21, 2011 | |
Last modified: | February 10, 2021 | |
This is version 213 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families