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263  structures 4788  species 1  interaction 7405  sequences 34  architectures

Family: dUTPase (PF00692)

Summary: dUTPase

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This is the Wikipedia entry entitled "DUTP diphosphatase". More...

DUTP diphosphatase Edit Wikipedia article

dUTP diphosphatase
Identifiers
EC number 3.6.1.23
CAS number 37289-34-2
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
dUTPase
PDB 1f7o EBI.jpg
crystal structures of feline immunodeficiency virus dutp pyrophosphatase and its nucleotide complexes in three crystal forms.
Identifiers
Symbol dUTPase
Pfam PF00692
Pfam clan CL0153
InterPro IPR008180
SCOP 1dup
SUPERFAMILY 1dup
dUTPase_2
PDB 1w2y EBI.jpg
the crystal structure of a complex of campylobacter jejuni dutpase with substrate analogue dupnhp
Identifiers
Symbol dUTPase_2
Pfam PF08761
Pfam clan CL0231
InterPro IPR014871
SCOP 1w2y
SUPERFAMILY 1w2y

In enzymology, a dUTP diphosphatase (EC 3.6.1.23) is an enzyme that catalyzes the chemical reaction

dUTP + H2O \rightleftharpoons dUMP + diphosphate

Thus, the two substrates of this enzyme are dUTP and H2O, whereas its two products are dUMP and diphosphate.

This enzyme belongs to the family of hydrolases, specifically those acting on acid anhydrides in phosphorus-containing anhydrides. The systematic name of this enzyme class is dUTP nucleotidohydrolase. Other names in common use include deoxyuridine-triphosphatase, dUTPase, dUTP pyrophosphatase, desoxyuridine 5'-triphosphate nucleotidohydrolase, and desoxyuridine 5'-triphosphatase. This enzyme participates in pyrimidine metabolism.

This enzyme has a dual function: on one hand, it removes dUTP from the deoxynucleotide pool, which reduces the probability of this base being incorporated into DNA by DNA polymerases, while on the other hand, it produces the dTTP precursor dUMP. Lack or inhibition of dUTPase action leads to harmful perturbations in the nucleotide pool resulting in increased uracil content of DNA that activates a hyperactive futile cycle of DNA repair.[1][2]

Structural studies[edit]

As of late 2007, 48 structures have been solved for this class of enzymes, with PDB accession codes 1DUC, 1DUD, 1DUN, 1DUP, 1DUT, 1EU5, 1EUW, 1F7D, 1F7K, 1F7N, 1F7O, 1F7P, 1F7Q, 1F7R, 1MQ7, 1OGH, 1OGK, 1OGL, 1PKH, 1PKJ, 1PKK, 1RN8, 1RNJ, 1SEH, 1SIX, 1SJN, 1SLH, 1SM8, 1SMC, 1SNF, 1SYL, 1VYQ, 1W2Y, 2BSY, 2BT1, 2CJE, 2D4L, 2D4M, 2D4N, 2HQU, 2HR6, 2HRM, 2OKB, 2OKD, 2OKE, 2OL0, 2OL1, and 2PY4.

There are at least two structurally distinct families of dUTPases. The crystal structure of human dUTPase reveals that each subunit of the dUTPase trimer folds into an eight-stranded jelly-roll beta barrel, with the C-terminal beta strands interchanged among the subunits. The structure is similar to that of the Escherichia coli enzyme, despite low sequence homology between the two enzymes.[3]

The second family has a novel all-alpha fold, members of this family are unrelated to the all-beta fold found in dUTPases of the majority of organisms.[4]

References[edit]

  1. ^ Vertessy BG, Toth J (2009). "Keeping uracil out of DNA". Accounts of Chemical Research 42 (1): 97–106. doi:10.1021/ar800114w. PMID 18837522. 
  2. ^ Vassylyev DG, Morikawa K (1996). "Precluding uracil from DNA". Structure 4 (12): 1381–5. doi:10.1016/S0969-2126(96)00145-1. PMID 8994964. 
  3. ^ Mol CD, Harris JM, McIntosh EM, Tainer JA (September 1996). "Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits". Structure 4 (9): 1077–92. doi:10.1016/S0969-2126(96)00114-1. PMID 8805593. 
  4. ^ Moroz, O. V.; Harkiolaki, M.; Galperin, M. Y.; Vagin, A. A.; González-Pacanowska, D.; Wilson, K. S. (2004). "The Crystal Structure of a Complex of Campylobacter jejuni dUTPase with Substrate Analogue Sheds Light on the Mechanism and Suggests the "Basic Module" for Dimeric d(C/U)TPases". Journal of Molecular Biology 342 (5): 1583–1597. doi:10.1016/j.jmb.2004.07.050. PMID 15364583.  edit

Further reading[edit]

This article incorporates text from the public domain Pfam and InterPro IPR008180

This article incorporates text from the public domain Pfam and InterPro IPR014871


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

dUTPase Provide feedback

dUTPase hydrolyses dUTP to dUMP and pyrophosphate.

Literature references

  1. Cedergren-Zeppezauer ES, Larsson G, Nyman PO, Dauter Z, Wilson KS; , Nature 1992;355:740-743.: Crystal structure of a dUTPase. PUBMED:1311056 EPMC:1311056

  2. Mol CD, Harris JM, McIntosh EM, Tainer JA; , Structure 1996;4:1077-1092.: Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits. PUBMED:8805593 EPMC:8805593


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008180

Synonym(s): dUTP diphosphatase, Deoxyuridine-triphosphatase

The essential enzyme dUTP pyrophosphatase (EC) is specific for dUTP and is critical for the fidelity of DNA replication and repair. dUTPase hydrolyzes dUTP to dUMP and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for dTTP biosynthesis. dUTPase decreases the intracellular concentration of dUPT so that uracil cannot be incorporated into DNA [PUBMED:8805593].

The crystal structure of human dUTPase reveals that each subunit of the dUTPase trimer folds into an eight-stranded jelly-roll beta barrel, with the C-terminal beta strands interchanged among the subunits. The structure is similar to that of the Escherichia coli enzyme, despite low sequence homology between the two enzymes [PUBMED:8805593].

Other enzymes like deoxycytidine triphosphate deaminase (dCTP) (EC) that specifically bind uridine also belong to this group suggesting that the signature may recognise a putative uridine-binding motif.

Some retroviruses encode dUTPases. Retroviral dUTPase is synthesised as part of POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, dUTPase and RNase H.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan dUTPase (CL0153), which contains the following 7 members:

Cytomega_UL84 DCD DUF570 dUTPase Herpes_ORF11 Herpes_U55 Herpes_UL82_83

Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(29)
Full
(7405)
Representative proteomes NCBI
(5446)
Meta
(3768)
RP15
(563)
RP35
(1093)
RP55
(1455)
RP75
(1771)
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Format an alignment

  Seed
(29)
Full
(7405)
Representative proteomes NCBI
(5446)
Meta
(3768)
RP15
(563)
RP35
(1093)
RP55
(1455)
RP75
(1771)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(29)
Full
(7405)
Representative proteomes NCBI
(5446)
Meta
(3768)
RP15
(563)
RP35
(1093)
RP55
(1455)
RP75
(1771)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_127 (release 2.1)
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 29
Number in full: 7405
Average length of the domain: 123.20 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 66.70 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.3 20.3
Noise cut-off 20.2 20.2
Model length: 129
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

dUTPase

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the dUTPase domain has been found. There are 263 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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