Fapy_DNA_glyco Formamidopyrimidine-DNA glycosylase N-terminal domain
SMART ACC:	SM000898
Description:	This entry represents the catalytic domain of DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Most damage to bases in DNA is repaired by the base excision repair pathway (PUBMED:15588838). These enzymes are primarily from bacteria, and have both DNA glycosylase activity and AP lyase activity. Examples include formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidation-damaged bases (N-glycosylase activity; ) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity; ). Fpg has a preference for oxidised purines, excising oxidized purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). ITs AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge (PUBMED:10921868). The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidized base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes (PUBMED:10921868). Fpg binds one ion of zinc at the C-terminus, which contains four conserved and essential cysteines (PUBMED:8473347), (PUBMED:7704272). Endonuclease VIII (Nei) has the same enzyme activities as Fpg above, but with a preference for oxidized pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine (PUBMED:15232006). These protein contains three structural domains: an N-terminal catalytic core domain, a central helix-two turn-helix (H2TH) module and a C-terminal zinc finger (see PDB:1K82) (PUBMED:11912217). The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. Residues that contact DNA are located in the catalytic domain and in a beta-hairpin loop formed by the zinc finger (PUBMED:12055620).
InterPro ACC:	IPR012319
InterPro abstract:	This entry represents the catalytic domain of DNA glycosylase/AP lyase enzymes including formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) are trifunctional DNA base excision repair enzymes that remove a wide range of oxidation-damaged bases (N-glycosylase activity; EC:3.2.2.23 … expand This entry represents the catalytic domain of DNA glycosylase/AP lyase enzymes including formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) are trifunctional DNA base excision repair enzymes that remove a wide range of oxidation-damaged bases (N-glycosylase activity; EC:3.2.2.23 ) and cleave both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity; EC:4.2.99.18 ). Fpg has a preference for oxidised purines, excising oxidised purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). Its AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge [ PUBMED:10921868 ]. The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidised base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes [ PUBMED:10921868 ]. Fpg binds one ion of zinc at the C-terminal, which contains four conserved and essential cysteines [ PUBMED:8473347 PUBMED:7704272 ]. Endonuclease VIII (Nei) has the same enzyme activities as Fpg ( EC:3.2.2 EC:4.2.99.18 ), but with a preference for oxidised pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine [ PUBMED:15232006 ]. These proteins contain three structural domains: an N-terminal catalytic core domain, a central helix-two turn-helix (H2TH) module and a C-terminal zinc finger [ PUBMED:11912217 ]. The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. Residues that contact DNA are located in the catalytic domain and in a β-hairpin loop formed by the zinc finger [ PUBMED:12055620 ]. collapse
GO process:	base-excision repair (GO:0006284)
GO function:	DNA N-glycosylase activity (GO:0019104), zinc ion binding (GO:0008270), DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0003906)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 28 602 Fapy_DNA_glyco domains in 28 602 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing Fapy_DNA_glyco domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing Fapy_DNA_glyco domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Predicted cellular role

Cellular role:	Transport

Relevant references for this domain

Primary literature for the Fapy_DNA_glyco domain is listed below. Automatically-derived, secondary literature is also available.

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a Fapy_DNA_glyco domain which could be assigned to a KEGG orthologous group, and not all proteins containing Fapy_DNA_glyco domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

Pfam	Fapy_DNA_glyco
InterPro	IPR012319