The N-terminal and internal 5'3'-exonuclease domains are commonly found together, and are most often associated with 5' to 3' nuclease activities. The XPG protein signatures are never found outside the '53EXO' domains. The latter are found in more diverse proteins [(PUBMED:7926735), (PUBMED:10322433), (PUBMED:8464724)]. The number of amino acids that separate the two 53EXO domains, and the presence of accompanying motifs allow the diagnosis of several protein families.
In the eubacterial type A DNA-polymerases, the N-terminal and internal domains are separated by a few amino acids, usually four. The pattern DNA_POLYMERASE_A (IPR001098) is always present towards the C terminus. Several eukaryotic structure-dependent endonucleases and exonucleases have the 53EXO domains separated by 24 to 27 amino acids, and the XPG protein signatures are always present. In several proteins from herpesviridae, the two 53EXO domains are separated by 50 to 120 amino acids. These proteins are implicated in the inhibition of the expression of the host genes. Eukaryotic DNA repair proteins with 600 to 700 amino acids between the 53_EXO domains all carry the XPG protein signatures.
Crystal structure of Thermus aquaticus DNA polymerase.
Nature. 1995; 376: 612-6
Display abstract
The DNA polymerase from Thermus aquaticus (Taq polymerase), famous for its use in the polymerase chain reaction, is homologous to Escherichia coli DNA polymerase I (pol I) Like pol I, Taq polymerase has a domain at its amino terminus (residues 1-290) that has 5' nuclease activity and a domain at its carboxy terminus that catalyses the polymerase reaction. Unlike pol I, the intervening domain in Taq polymerase has lost the editing 3'-5' exonuclease activity. Although the structure of the Klenow fragment of pol I has been known for ten years, that of the intact pol I has proved more elusive. The structure of Taq polymerase determined here at 2.4 A resolution shows that the structures of the polymerase domains of the thermostable enzyme and of the Klenow fragment are nearly identical, whereas the catalytically critical carboxylate residues that bind two metal ions are missing from the remnants of the 3'-5' exonuclease active site of Taq polymerase. The first view of the 5' nuclease domain, responsible for excising the Okazaki RNA in lagging-strand DNA replication, shows a cluster of conserved divalent metal-ion-binding carboxylates at the bottom of a cleft. The location of this 5'-nuclease active site some 70 A from the polymerase active site in this crystal form highlights the unanswered question of how this domain works in concert with the polymerase domain to produce a duplex DNA product that contains only a nick.
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 53EXOc domain which could be assigned to a KEGG orthologous group, and not all proteins containing 53EXOc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
