35EXOc3'-5' exonuclease |
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SMART accession number: | SM00474 |
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Description: | 3\' -5' exonuclease proofreading domain present in DNA polymerase I, Werner syndrome helicase, RNase D and other enzymes |
Interpro abstract (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) ]. Werner syndrome is a human genetic disorder causing premature aging; the WRN protein has helicase activity in the 3'-5' direction [ (PUBMED:9288107) (PUBMED:9224595) ]. 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 [ (PUBMED:9697700) ]. 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. |
GO process: | nucleobase-containing compound metabolic process (GO:0006139) |
GO function: | nucleic acid binding (GO:0003676), 3'-5' exonuclease activity (GO:0008408) |
Family alignment: |
There are 40504 35EXOc domains in 40484 proteins in SMART's nrdb database.
Click on the following links for more information.
- Evolution (species in which this domain is found)
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Taxonomic distribution of proteins containing 35EXOc domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with 35EXOc domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing 35EXOc domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
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Cellular role: replication
- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Brautigam CA, Sun S, Piccirilli JA, Steitz TA
- Structures of normal single-stranded DNA and deoxyribo-3'-S-phosphorothiolates bound to the 3'-5' exonucleolytic active site of DNA polymerase I from Escherichia coli.
- Biochemistry. 1999; 38: 696-704
- Display abstract
The interaction of a divalent metal ion with a leaving 3' oxygen is a central component of several proposed mechanisms of phosphoryl transfer. In support of this are recent kinetic studies showing that thiophilic metal ions (e.g., Mn2+) stimulate the hydrolysis of compounds in which sulfur takes the place of the leaving oxygen. To examine the structural basis of this phenomenon, we have solved four crystal structures of single-stranded DNA's containing either oxygen or sulfur at a 3'-bridging position bound in conjunction with various metal ions at the 3'-5' exonucleolytic active site of the Klenow fragment (KF) of DNA polymerase I from Escherichia coli. Two structures of normal ssDNA bound to KF in the presence of Zn2+ and Mn2+ or Zn2+ alone were refined at 2.6- and 2.25-A resolution, respectively. They serve as standards for comparison with other Mn2+- and Zn2+-containing structures. In these cases, Mn2+ and Zn2+ bind at metal ion site B in a nearly identical position to Mg2+ (Brautigam and Steitz (1998) J. Mol. Biol. 277, 363-377). Two structures of KF bound to a deoxyoligonucleotide that contained a 3'-bridging sulfur at the scissile phosphate were refined at 2.03-A resolution. Although the bridging sulfur compounds bind in a manner very similar to that of the normal oligonucleotides, the presence of the sulfur changes the metal ion binding properties of the active site such that Mn2+ and Zn2+ are observed at metal ion site B, but Mg2+ is not. It therefore appears that the ability of the bridging sulfur compounds to exclude nonthiophilic metal ions from metal ion site B explains the low activity of KF exonuclease on these substrates in the presence of Mg2+ (Curley et al. (1997) J. Am. Chem. Soc. 119, 12691-12692) and that the 3'-bridging atom of the substrate is influencing the binding of metal ion B prior to catalysis.
- Moser MJ, Holley WR, Chatterjee A, Mian IS
- The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains.
- Nucleic Acids Res. 1997; 25: 5110-8
- Display abstract
Prior sequence analysis studies have suggested that bacterial ribonuclease (RNase) Ds comprise a complete domain that is found also in Homo sapiens polymyositis-scleroderma overlap syndrome 100 kDa autoantigen and Werner syndrome protein. This RNase D 3'-->5' exoribonuclease domain was predicted to have a structure and mechanism of action similar to the 3'-->5' exodeoxyibonuclease (proofreading) domain of DNA polymerases. Here, hidden Markov model (HMM) and phylogenetic studies have been used to identify and characterise other sequences that may possess this exonuclease domain. Results indicate that it is also present in the RNase T family; Borrelia burgdorferi P93 protein, an immunodominant antigen in Lyme disease; bacteriophage T4 dexA and Escherichia coli exonuclease I, processive 3'-->5' exodeoxyribonucleases that degrade single-stranded DNA; Bacillus subtilis dinG, a probable helicase involved in DNA repair and possibly replication, and peptide synthase 1; Saccharomyces cerevisiae Pab1p-dependent poly(A) nuclease PAN2 subunit, required for shortening mRNA poly(A) tails; Caenorhabditis elegans and Mus musculus CAF1, transcription factor CCR4-associated factor 1; Xenopus laevis XPMC2, prevention of mitotic catastrophe in fission yeast; Drosophila melanogaster egalitarian, oocyte specification and axis determination, and exuperantia, establishment of oocyte polarity; H.sapiens HEM45, expressed in tumour cell lines and uterus and regulated by oestrogen; and 31 open reading frames including one in Methanococcus jannaschii . Examination of a multiple sequence alignment and two three-dimensional structures of proofreading domains has allowed definition of the core sequence, structural and functional elements of this exonuclease domain.
- Braithwaite DK, Ito J
- Compilation, alignment, and phylogenetic relationships of DNA polymerases.
- Nucleic Acids Res. 1993; 21: 787-802
- Ollis DL, Brick P, Hamlin R, Xuong NG, Steitz TA
- Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP.
- Nature. 1985; 313: 762-6
- Display abstract
The 3.3-A resolution crystal structure of the large proteolytic fragment of Escherichia coli DNA polymerase I complexed with deoxythymidine monophosphate consists of two domains, the smaller of which binds zinc-deoxythymidine monophosphate. The most striking feature of the larger domain is a deep crevice of the appropriate size and shape for binding double-stranded B-DNA. A flexible subdomain may allow the enzyme to surround completely the DNA substrate, thereby allowing processive nucleotide polymerization without enzyme dissociation.
- Metabolism (metabolic pathways involving proteins which contain this domain)
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Click the image to view the interactive version of the map in iPath% proteins involved KEGG pathway ID Description 33.33 map00240 Pyrimidine metabolism 33.33 map03030 DNA replication 33.33 map00230 Purine metabolism This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with 35EXOc domain which could be assigned to a KEGG orthologous group, and not all proteins containing 35EXOc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of 35EXOc domains in PDB
PDB code Main view Title 1d8y CRYSTAL STRUCTURE OF THE COMPLEX OF DNA POLYMERASE I KLENOW FRAGMENT WITH DNA 1d9d CRYSTALL STRUCTURE OF THE COMPLEX OF DNA POLYMERASE I KLENOW FRAGMENT WITH SHORT DNA FRAGMENT CARRYING 2'-0-AMINOPROPYL-RNA MODIFICATIONS 5'-D(TCG)-AP(AUC)-3' 1d9f CRYSTAL STRUCTURE OF THE COMPLEX OF DNA POLYMERASE I KLENOW FRAGMENT WITH DNA TETRAMER CARRYING 2'-O-(3-AMINOPROPYL)-RNA MODIFICATION 5'-D(TT)-AP(U)-D(T)-3' 1dpi STRUCTURE OF LARGE FRAGMENT OF ESCHERICHIA COLI DNA POLYMERASE I COMPLEXED WITH D/TMP 1kfd CRYSTAL STRUCTURES OF THE KLENOW FRAGMENT OF DNA POLYMERASE I COMPLEXED WITH DEOXYNUCLEOSIDE TRIPHOSPHATE AND PYROPHOSPHATE 1kfs DNA POLYMERASE I KLENOW FRAGMENT (E.C.2.7.7.7) MUTANT/DNA COMPLEX 1kln DNA POLYMERASE I KLENOW FRAGMENT (E.C.2.7.7.7) MUTANT/DNA COMPLEX 1krp DNA POLYMERASE I KLENOW FRAGMENT (E.C.2.7.7.7) MUTANT/DNA COMPLEX 1ksp DNA POLYMERASE I KLENOW FRAGMENT (E.C.2.7.7.7) MUTANT/DNA COMPLEX 1l3s Crystal Structure of Bacillus DNA Polymerase I Fragment complexed to 9 base pairs of duplex DNA. 1l3t Crystal Structure of Bacillus DNA Polymerase I Fragment product complex with 10 base pairs of duplex DNA following addition of a single dTTP residue 1l3u Crystal Structure of Bacillus DNA Polymerase I Fragment product complex with 11 base pairs of duplex DNA following addition of a dTTP and a dATP residue. 1l3v Crystal Structure of Bacillus DNA Polymerase I Fragment product complex with 15 base pairs of duplex DNA following addition of dTTP, dATP, dCTP, and dGTP residues. 1l5u Crystal Structure of Bacillus DNA Polymerase I Fragment product complex with 12 base pairs of duplex DNA following addition of a dTTP, a dATP, and a dCTP residue. 1lv5 Crystal Structure of the Closed Conformation of Bacillus DNA Polymerase I Fragment Bound to DNA and dCTP 1njw GUANINE-THYMINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1njx THYMINE-GUANINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1njy THYMINE-THYMINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1njz CYTOSINE-THYMINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1nk0 ADENINE-GUANINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1nk4 GUANINE-GUANINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1nk5 ADENINE-ADENINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1nk6 CYTOSINE-CYTOSINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1nk7 GUANINE-ADENINE MISMATCH AT THE POLYMERASE ACTIVE SITE 1nk8 A BACILLUS DNA POLYMERASE I PRODUCT COMPLEX BOUND TO A GUANINE-THYMINE MISMATCH AFTER A SINGLE ROUND OF PRIMER EXTENSION, FOLLOWING INCORPORATION OF DCTP. 1nk9 A BACILLUS DNA POLYMERASE I PRODUCT COMPLEX BOUND TO A GUANINE-THYMINE MISMATCH AFTER TWO ROUNDS OF PRIMER EXTENSION, FOLLOWING INCORPORATION OF DCTP AND DGTP. 1nkb A BACILLUS DNA POLYMERASE I PRODUCT COMPLEX BOUND TO A GUANINE-THYMINE MISMATCH AFTER THREE ROUNDS OF PRIMER EXTENSION, FOLLOWING INCORPORATION OF DCTP, DGTP, AND DTTP. 1nkc A BACILLUS DNA POLYMERASE I PRODUCT COMPLEX BOUND TO A GUANINE-THYMINE MISMATCH AFTER FIVE ROUNDS OF PRIMER EXTENSION, FOLLOWING INCORPORATION OF DCTP, DGTP, DTTP, AND DATP. 1nke A BACILLUS DNA POLYMERASE I PRODUCT COMPLEX BOUND TO A CYTOSINE-THYMINE MISMATCH AFTER A SINGLE ROUND OF PRIMER EXTENSION, FOLLOWING INCORPORATION OF DCTP. 1qsl KLENOW FRAGMENT COMPLEXED WITH SINGLE-STRANDED SUBSTRATE AND EUROPIUM (III) ION 1u45 8oxoguanine at the pre-insertion site of the polymerase active site 1u47 cytosine-8-Oxoguanine base pair at the polymerase active site 1u48 Extension of a cytosine-8-oxoguanine base pair 1u49 Adenine-8oxoguanine mismatch at the polymerase active site 1u4b Extension of an adenine-8oxoguanine mismatch 1ua0 Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase 1ua1 Structure of aminofluorene adduct paired opposite cytosine at the polymerase active site. 1xc9 Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication 1xwl BACILLUS STEAROTHERMOPHILUS (NEWLY IDENTIFIED STRAIN AS YET UNNAMED) DNA POLYMERASE FRAGMENT 1yt3 Crystal Structure of Escherichia coli RNase D, an exoribonuclease involved in structured RNA processing 2bdp CRYSTAL STRUCTURE OF BACILLUS DNA POLYMERASE I FRAGMENT COMPLEXED TO 9 BASE PAIRS OF DUPLEX DNA 2e6l structure of mouse WRN exonuclease domain 2e6m structure of mouse werner exonuclease domain 2fbt WRN exonuclease 2fbv WRN exonuclease, Mn complex 2fbx WRN exonuclease, Mg complex 2fby WRN exonuclease, Eu complex 2fc0 WRN exonuclease, Mn dGMP complex 2hbj Structure of the yeast nuclear exosome component, Rrp6p, reveals an interplay between the active site and the HRDC domain 2hbk Structure of the yeast nuclear exosome component, Rrp6p, reveals an interplay between the active site and the HRDC domain; Protein in complex with Mn 2hbl Structure of the yeast nuclear exosome component, Rrp6p, reveals an interplay between the active site and the HRDC domain; Protein in complex with Mn, Zn, and AMP 2hbm Structure of the yeast nuclear exosome component, Rrp6p, reveals an interplay between the active site and the HRDC domain; Protein in complex with Mn, Zn, and UMP 2hhq O6-methyl-guanine:T pair in the polymerase-10 basepair position 2hhs O6-methyl:C pair in the polymerase-10 basepair position 2hht C:O6-methyl-guanine pair in the polymerase-2 basepair position 2hhu C:O6-methyl-guanine in the polymerase postinsertion site (-1 basepair position) 2hhv T:O6-methyl-guanine in the polymerase-2 basepair position 2hhw ddTTP:O6-methyl-guanine pair in the polymerase active site, in the closed conformation 2hhx O6-methyl-guanine in the polymerase template preinsertion site 2hvh ddCTP:O6MeG pair in the polymerase active site (0 position) 2hvi ddCTP:G pair in the polymerase active site (0 position) 2hw3 T:O6-methyl-guanine pair in the polymerase postinsertion site (-1 basepair position) 2kfn KLENOW FRAGMENT WITH BRIDGING-SULFUR SUBSTRATE AND MANGANESE 2kfz KLENOW FRAGMENT WITH BRIDGING-SULFUR SUBSTRATE AND ZINC ONLY 2kzm KLENOW FRAGMENT WITH NORMAL SUBSTRATE AND ZINC AND MANGANESE 2kzz KLENOW FRAGMENT WITH NORMAL SUBSTRATE AND ZINC ONLY 2xo7 Crystal structure of a dA:O-allylhydroxylamine-dC basepair in complex with fragment DNA polymerase I from Bacillus stearothermophilus 2xy5 Crystal structure of an artificial salen-copper basepair in complex with fragment DNA polymerase I from Bacillus stearothermophilus 2xy6 Crystal structure of a salicylic aldehyde basepair in complex with fragment DNA polymerase I from Bacillus stearothermophilus 2xy7 Crystal structure of a salicylic aldehyde base in the pre-insertion site of fragment DNA polymerase I from Bacillus stearothermophilus 2y1i Crystal structure of a S-diastereomer analogue of the spore photoproduct in complex with fragment DNA polymerase I from Bacillus stearothermophilus 2y1j Crystal structure of a R-diastereomer analogue of the spore photoproduct in complex with fragment DNA polymerase I from Bacillus stearothermophilus 3bdp DNA POLYMERASE I/DNA COMPLEX 3cym Crystal structure of protein BAD_0989 from Bifidobacterium adolescentis 3eyz Cocrystal structure of Bacillus fragment DNA polymerase I with duplex DNA (open form) 3ez5 Cocrystal structure of Bacillus fragment DNA polymerase I with duplex DNA , dCTP, and zinc (closed form). 3hp6 Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus F710Y mutant bound to G:T mismatch 3hpo Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus Y714S mutant bound to G:T mismatch 3ht3 Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus V713P mutant bound to G:dCTP 3pv8 Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to DNA and ddTTP-dA in Closed Conformation 3px0 Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to DNA and dCTP-dA Mismatch (tautomer) in Closed Conformation 3px4 Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to DNA and ddCTP-dA Mismatch (wobble) in Ajar Conformation 3px6 Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to DNA and ddCTP-dA Mismatch (tautomer) in Closed Conformation 3saf Crystal structure of the human RRP6 catalytic domain with D313N mutation in the active site 3sag Crystal structure of the human RRP6 catalytic domain with D313N mutation in the active site 3sah Crystal structure of the human RRP6 catalytic domain with Y436A mutation in the catalytic site 3tan Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to Duplex DNA with Cytosine-Adenine Mismatch at (n-1) Position 3tap Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to Duplex DNA with Cytosine-Adenine Mismatch at (n-3) Position 3taq Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to Duplex DNA with Cytosine-Adenine Mismatch at (n-4) Position 3tar Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to Duplex DNA with Cytosine-Adenine Mismatch at (n-6) Position 3thv Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to DNA and ddATP-dT in Closed Conformation 3ti0 Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to DNA and ddGTP-dC in Closed Conformation 4b9l Structure of the high fidelity DNA polymerase I with the oxidative formamidopyrimidine-dA DNA lesion in the pre-insertion site. 4b9m Structure of the high fidelity DNA polymerase I with an oxidative formamidopyrimidine-dA DNA lesion -thymine basepair in the post- insertion site. 4b9n Structure of the high fidelity DNA polymerase I correctly bypassing the oxidative formamidopyrimidine-dA DNA lesion. 4b9s Structure of the high fidelity DNA polymerase I with an oxidative formamidopyrimidine-dG DNA lesion outside of the pre-insertion site. 4b9t Structure of the high fidelity DNA polymerase I with an oxidative formamidopyrimidine-dG DNA lesion -dC basepair in the post-insertion site. 4b9u Structure of the high fidelity DNA polymerase I with an oxidative formamidopyrimidine-dG DNA lesion -dA basepair in the post-insertion site. 4b9v Structure of the high fidelity DNA polymerase I with extending from an oxidative formamidopyrimidine-dG DNA lesion -dA basepair. 4bdp CRYSTAL STRUCTURE OF BACILLUS DNA POLYMERASE I FRAGMENT COMPLEXED TO 11 BASE PAIRS OF DUPLEX DNA AFTER ADDITION OF TWO DATP RESIDUES 4dqi Ternary complex of Bacillus DNA Polymerase I Large Fragment, DNA duplex, and dCTP (paired with dG of template) 4dqp Ternary complex of Bacillus DNA Polymerase I Large Fragment, DNA duplex, and ddCTP (paired with dG of template) 4dqq Ternary complex of Bacillus DNA Polymerase I Large Fragment E658A, DNA duplex, and rCTP (paired with dG of template) in presence of Mg2+ 4dqr Ternary complex of Bacillus DNA Polymerase I Large Fragment E658A, DNA duplex, and rCTP (paired with dG of template) in presence of Mn2+ 4dqs Binary complex of Bacillus DNA Polymerase I Large Fragment and duplex DNA with rC in primer terminus paired with dG of template 4ds4 Ternary complex of Bacillus DNA Polymerase I Large Fragment, DNA duplex, and rCTP in presence of Mn2+ 4ds5 Ternary complex of Bacillus DNA Polymerase I Large Fragment, DNA duplex, and rCTP in presence of Mg2+ 4dse Ternary complex of Bacillus DNA Polymerase I Large Fragment F710Y, DNA duplex, and rCTP (paired with dG of template) in presence of Mg2+ 4dsf Ternary complex of Bacillus DNA Polymerase I Large Fragment F710Y, DNA duplex, and rCTP (paired with dG of template) in presence of Mn2+ 4dsi Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus with duplex DNA, Se-dGTP and Calcium 4dsj Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus with duplex DNA, dGTP and Calcium 4dsk Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus with duplex DNA, PPi and Calcium 4dsl Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus with duplex DNA and Calcium 4dwi Crystal structure of fragment DNA polymerase I from Bacillus stearothermophilus with self complementary DNA, Se-dGTP and Calcium 4e0d Binary complex of Bacillus DNA Polymerase I Large Fragment E658A and duplex DNA 4ez6 Bacillus DNA Polymerase I Large Fragment Complex 1 4ez9 Bacillus DNA Polymerase I Large Fragment Complex 2 4f2r DNA Polymerase I Large Fragment complex 3 4f2s DNA Polymerase I Large Fragment complex 4 4f3o DNA Polymerase I Large Fragment Complex 5 4f4k DNA Polymerase I Large Fragment Complex 6 4f8r Bacillus DNA Polymerase I Large Fragment complex 7 4nlb Crystal structure of the catalytic core of RRP6 from Trypanosoma brucei 4nlc Crystal structure of the catalytic core of RRP6 from Trypanosoma brucei, mutant C496S 4o0i 4O0I 4oo1 4OO1 4uqg 4UQG 4yfu 4YFU 5c0w 5C0W 5c0x 5C0X 5c0y 5C0Y 5dkt 5DKT 5dku 5DKU 5fiq 5FIQ 5fis 5FIS 5k36 5K36 - Links (links to other resources describing this domain)
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PFAM 3_5_exonuclease INTERPRO IPR002562