Summary

3'-5' exonuclease

This domain is responsible for the 3'-5' exonuclease proofreading activity of E. coli DNA polymerase I (polI) and other enzymes, it catalyses the hydrolysis of unpaired or mismatched nucleotides. This domain consists of the amino-terminal half of the Klenow fragment in E. coli polI it is also found in the Werner syndrome helicase (WRN), focus forming activity 1 protein (FFA-1) and ribonuclease D (RNase D). Werner syndrome is a human genetic disorder causing premature aging; the WRN protein has helicase activity in the 3'-5' direction [4,5]. The FFA-1 protein is required for formation of a replication foci and also has helicase activity; it is a homologue of the WRN protein [3]. RNase D is a 3'-5' exonuclease involved in tRNA processing. Also found in this family is the autoantigen PM/Scl thought to be involved in polymyositis-scleroderma overlap syndrome.

Literature references

Ollis DL, Brick P, Hamlin R, Xuong NG, Steitz TA; , Nature 1985;313:762-766.: Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP. PUBMED:3883192
Moser MJ, Holley WR, Chatterjee A, Mian IS; , Nucleic Acids Res 1997;25:5110-5118.: The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains. PUBMED:9396823
Yan H, Chen CY, Kobayashi R, Newport J; , Nat Genet 1998;19:375-378.: Replication focus-forming activity 1 and the Werner syndrome gene product PUBMED:9697700
Gray MD, Shen JC, Kamath-Loeb AS, Blank A, Sopher BL, Martin GM, Oshima J, Loeb LA; , Nat Genet 1997;17:100-103.: The Werner syndrome protein is a DNA helicase. PUBMED:9288107
Suzuki N, Shimamoto A, Imamura O, Kuromitsu J, Kitao S, Goto M, Furuichi Y; , Nucleic Acids Res 1997;25:2973-2978.: DNA helicase activity in Werner's syndrome gene product synthesized in a baculovirus system. PUBMED:9224595

InterPro entry IPR002562

This domain is responsible for the 3'-5' exonuclease proofreading activity of Escherichia coli DNA polymerase I (polI) and other enzymes, it catalyses the hydrolysis of unpaired or mismatched nucleotides. This domain consists of the amino-terminal half of the Klenow fragment in E. coli polI it is also found in the Werner syndrome helicase (WRN), focus forming activity 1 protein (FFA-1) and ribonuclease D (RNase D) PUBMED:9697700.

Clan

This family is a member of clan RNase_H (CL0219), which contains the following 25 members:

3_5_exonuc CAF1 DDE DNA_pol_B_exo DUF458 Exon_PolB Exonuc_X-T Mu_transposase MULE Phage_Lacto_M3 Piwi Plant_tran Pox_A22 RNase_HII RnaseH RuvC rve Transposase_11 Transposase_12 Transposase_25 Transposase_27 Transposase_29 Transposase_mut UPF0236 Ydc2-catalyt

Gene Ontology

Cellular component	intracellular (GO:0005622)
Molecular function	3'-5' exonuclease activity (GO:0008408)
Molecular function	nucleic acid binding (GO:0003676)
Biological process	nucleobase, nucleoside, nucleotide and nucleic acid metabolic process (GO:0006139)

External database links

HOMSTRAD:	dpo1
PANDIT:	PF01612
SCOP:	1dpi
SYSTERS:	3_5_exonuc

Domain organisation

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

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (28) Full (2730) NCBI (8037) Metagenomics (5682)
Viewer:

Formatting options

Alignment:	Seed (28) Full (2730)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (28) Full (2730) NCBI (8037) Metagenomics (5682)
Full length sequences	Full-sequences (2730)

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 HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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

Seed source:

Pfam-B_659 (release 4.1)

Previous IDs:

3_5_exonuclease;

Type:

Domain

Author:

Bashton M, Bateman A, Griffiths-Jones SR

Number in seed:

28

Number in full:

2730

Average length of the domain:

173.00 aa

Average identity of full alignment:

21 %

Average coverage of the sequence by the domain:

27.71 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.4	20.4
Trusted cut-off	20.4	20.4
Noise cut-off	20.3	20.3

Model length:

174

Family (HMM) version:

13

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Interactions

There are 2 interactions for this family. More...

DNA_pol_A HRDC

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 MSD 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 3_5_exonuc domain has been found.

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Family: 3_5_exonuc (PF01612)

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