Reviewed,
UniProtKB/Swiss-Prot P33316 (DUT_HUMAN)
Last modified
June 16, 2009.
Version 99.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial Short name=dUTPase EC=3.6.1.23 Alternative name(s): dUTP pyrophosphatase | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 252 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | 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. |
| Catalytic activity | dUTP + H2O = dUMP + diphosphate. |
| Cofactor | Magnesium. |
| Enzyme regulation | Phosphorylation is necessary for activity. |
| Pathway | Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP route): step 2/2. |
| Subcellular location | Isoform 1: Mitochondrion. Isoform 2: Nucleus. |
| Tissue specificity | Found in a variety of tissues. |
| Post-translational modification | Phosphorylation in mature T-cells occur in a cell cycle-dependent manner. |
| Sequence similarities | Belongs to the dUTPase family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Nucleotide metabolism |
| Cellular component | Mitochondrion Nucleus |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Transit peptide |
| Ligand | Magnesium |
| Molecular function | Hydrolase |
| PTM | Phosphoprotein |
| Technical term | 3D-structure Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | DNA replication Ref.9 Traceable author statement. Source: ProtInc dUTP metabolic processInferred from electronic annotation. Source: InterPro |
| Cellular component | cytosol Ref.1 Inferred from Experiment. Source: Reactome mitochondrion Ref.1Traceable author statement. Source: ProtInc nucleus Ref.1Traceable author statement. Source: ProtInc |
| Molecular function | dUTP diphosphatase activity Ref.1 Inferred from Experiment. Source: Reactome magnesium ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P33316-1) 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. | ||||||
| Isoform 2 (identifier: P33316-2) 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. | ||||||
| Isoform 3 (identifier: P33316-3) The sequence of this isoform differs from the canonical sequence as follows: 29-47: TAEGRSRGTLRARPAPRPP → ARQRAEAAVLSGPGPPLGR |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 69 | 69 | Mitochondrion | ||||||||||||||||||||||||||||||||
| Chain | 70 – 252 | 183 | Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial | PRO_0000007392 | |||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||
| Modified residue | 99 | 1 | Phosphoserine Ref.12 | ||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 93 | 93 | MTPLC…PAPGP → MPCSE in isoform 2. | VSP_001324 | |||||||||||||||||||||||||||||||
| Alternative sequence | 29 – 47 | 19 | TAEGR…APRPP → ARQRAEAAVLSGPGPPLGR in isoform 3. | VSP_035458 | |||||||||||||||||||||||||||||||
| Natural variant | 100 | 1 | P → S Ref.6 | VAR_022314 | |||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||
| Beta strand | 113 – 120 | 8 | |||||||||||||||||||||||||||||||||
| Beta strand | 134 – 139 | 6 | |||||||||||||||||||||||||||||||||
| Beta strand | 144 – 146 | 3 | |||||||||||||||||||||||||||||||||
| Beta strand | 150 – 155 | 6 | |||||||||||||||||||||||||||||||||
| Beta strand | 158 – 161 | 4 | |||||||||||||||||||||||||||||||||
| Beta strand | 166 – 171 | 6 | |||||||||||||||||||||||||||||||||
| Helix | 174 – 180 | 7 | |||||||||||||||||||||||||||||||||
| Beta strand | 182 – 185 | 4 | |||||||||||||||||||||||||||||||||
| Beta strand | 198 – 203 | 6 | |||||||||||||||||||||||||||||||||
| Beta strand | 205 – 207 | 3 | |||||||||||||||||||||||||||||||||
| Beta strand | 209 – 211 | 3 | |||||||||||||||||||||||||||||||||
| Beta strand | 216 – 225 | 10 | |||||||||||||||||||||||||||||||||
| Beta strand | 229 – 232 | 4 | |||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Characterization of distinct nuclear and mitochondrial forms of human deoxyuridine triphosphate nucleotidohydrolase." Ladner R.D., McNulty D.E., Carr S.A., Roberts G.D., Caradonna S.J. J. Biol. Chem. 271:7745-7751(1996) [PubMed: 8631816] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE. Tissue: T-cell. |
| [2] | "Assignment of the human dUTPase gene (DUT) to chromosome 15q15-q21. 1 by fluorescence in situ hybridization." Cohen D., Heng H.H.Q., Shi X.-M., McIntosh E.M., Tsui L.-C., Pearlman R.E. Genomics 40:213-215(1997) [PubMed: 9070952] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). |
| [3] | "Human genomic nuclear and mitochondria dUTPase gene." Pearlman R.E. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2). |
| [4] | "The human dUTPase gene encodes both nuclear and mitochondrial isoforms: differential expression of the isoforms and characterization of a cDNA encoding the mitochondrial species." Ladner R.D., Caradonna S.J. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). |
| [5] | "Unknown transcriptional variant of nuclear dUTPase in human osteosarcoma." Chano T., Okabe H., Baldini N., Lapucci C., Scotlandi K., Serra M., Saeki Y. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). |
| [6] | NIEHS SNPs program Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-100. |
| [7] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Brain, Eye and Urinary bladder. |
| [9] | "Human dUTP pyrophosphatase: cDNA sequence and potential biological importance of the enzyme." McIntosh E.M., Ager D.D., Gadsden M.H., Haynes R.H. Proc. Natl. Acad. Sci. U.S.A. 89:8020-8024(1992) [PubMed: 1325640] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-252. |
| [10] | Erratum McIntosh E.M., Ager D.D., Gadsden M.H., Haynes R.H. Proc. Natl. Acad. Sci. U.S.A. 90:4328-4328(1993) |
| [11] | "Maturation stage and proliferation-dependent expression of dUTPase in human T cells." Strahler J.R., Zhu X.-X., Wang Y.K., Hora N., Andrews P.C., Roseman N.A., Neel J.V., Turka L., Hanash S.M. Proc. Natl. Acad. Sci. U.S.A. 90:4991-4995(1993) [PubMed: 8389461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-252, PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION. Tissue: Lymphocyte. |
| [12] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, MASS SPECTROMETRY. Tissue: Epithelium. |
| [13] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [14] | "Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits." Mol C.D., Harris J.M., McIntosh E.M., Tainer J.A. Structure 4:1077-1092(1996) [PubMed: 8805593] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 112-252. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| U31930 mRNA. Translation: AAC50418.1. U62891 mRNA. Translation: AAC51123.1. AF018432 AF018431 Genomic DNA. Translation: AAB71393.1. AF018432 AF018431 Genomic DNA. Translation: AAB71394.1. U90223 mRNA. Translation: AAB94642.1. U90224 Genomic DNA. Translation: AAB93866.1. U90224 Genomic DNA. Translation: AAB93867.1. AB049113 mRNA. Translation: BAB13724.1. AY935242 Genomic DNA. Translation: AAX14045.1. CH471082 Genomic DNA. Translation: EAW77350.1. 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. | |||||||||||||||||||||||||
| IPI | IPI00013679. IPI00375015. IPI00749113. | ||||||||||||||||||||||||
| PIR | A46256. G02777. | ||||||||||||||||||||||||
| RefSeq | NP_001020419.1. NP_001939.1. | ||||||||||||||||||||||||
| UniGene | Hs.527980 | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
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| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| IntAct | P33316. 5 interactions. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | P33316. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PeptideAtlas | P33316. | ||||||||||||||||||||||||
| PRIDE | P33316. | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENSG00000128951. Homo sapiens. [Contig view] | ||||||||||||||||||||||||
| GeneID | 1854. | ||||||||||||||||||||||||
| KEGG | hsa:1854. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| GeneCards | GC15P046410. | ||||||||||||||||||||||||
| H-InvDB | HIX0031255. | ||||||||||||||||||||||||
| HGNC | HGNC:3078. DUT. | ||||||||||||||||||||||||
| MIM | 601266. gene. | ||||||||||||||||||||||||
| PharmGKB | PA151. | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| HOVERGEN | P33316. | ||||||||||||||||||||||||
| OMA | P33316. MQLRFAR. | ||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||
| BRENDA | 3.6.1.23. 247. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | P33316. | ||||||||||||||||||||||||
| Bgee | P33316. | ||||||||||||||||||||||||
| CleanEx | HS_DUT. | ||||||||||||||||||||||||
| GermOnline | ENSG00000128951. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR008180. DeoxyUTPase. IPR008181. dUTP_pyrophosphatase_subfam_1. [Graphical view] | ||||||||||||||||||||||||
| Pfam | PF00692. dUTPase. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProDom | PD004900. dCTP_deaminase. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||||||||||||||
| TIGRFAMs | TIGR00576. dut. 1 hit. | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||
| NextBio | 7591. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | DUT_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P33316 Secondary accession number(s): O14785 Q96Q81 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 15 Human chromosome 15: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| 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 |

Clusters with


