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P05523 (FPG_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Formamidopyrimidine-DNA glycosylase

Short name=Fapy-DNA glycosylase
EC=3.2.2.23
Alternative name(s):
DNA-(apurinic or apyrimidinic site) lyase MutM
Short name=AP lyase MutM
EC=4.2.99.18
Gene names
Name:mutM
Synonyms:fpg
Ordered Locus Names:b3635, JW3610
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length269 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG) and its derivatives such as guanidinohydantoin:C and spiroiminodihydantoin:C, however it also acts on thymine glycol:G, 5,6-dihydrouracil:G and 5-hydroxyuracil:G. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves 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. Cleaves ssDNA containing an AP site. Ref.7 Ref.10

Catalytic activity

Hydrolysis of DNA containing ring-opened 7-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine. HAMAP-Rule MF_00103

The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. HAMAP-Rule MF_00103

Cofactor

Binds 1 zinc ion per subunit. Ref.7

Subunit structure

Monomer. Ref.7

Domain

The zinc-finger is necessary for DNA binding. HAMAP-Rule MF_00103

Sequence similarities

Belongs to the FPG family.

Contains 1 FPG-type zinc finger.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionGlycosidase
Hydrolase
Lyase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process, endonucleolytic

Inferred from direct assay Ref.7PubMed 1731864PubMed 8034633Ref.8. Source: GOC

base-excision repair, AP site formation

Inferred from direct assay Ref.7. Source: EcoCyc

cellular response to DNA damage stimulus

Inferred from direct assay PubMed 1731864. Source: EcoliWiki

nucleic acid phosphodiester bond hydrolysis

Inferred from direct assay PubMed 1731864PubMed 2664776Ref.8. Source: GOC

nucleotide-excision repair

Inferred from electronic annotation. Source: InterPro

   Molecular_functionDNA N-glycosylase activity

Inferred from direct assay PubMed 10862773PubMed 2664776Ref.8. Source: EcoliWiki

DNA-(apurinic or apyrimidinic site) lyase activity

Inferred from direct assay PubMed 1731864Ref.8. Source: EcoliWiki

damaged DNA binding

Inferred from direct assay PubMed 8332499. Source: EcoCyc

endonuclease activity

Inferred from direct assay PubMed 1731864PubMed 2664776Ref.8. Source: EcoliWiki

metal ion binding

Inferred from direct assay Ref.8. Source: EcoliWiki

oxidized purine nucleobase lesion DNA N-glycosylase activity

Inferred from direct assay Ref.7. Source: EcoCyc

oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity

Inferred from direct assay PubMed 8034633. Source: EcoCyc

zinc ion binding

Inferred from direct assay Ref.8. Source: EcoliWiki

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 269268Formamidopyrimidine-DNA glycosylase HAMAP-Rule MF_00103
PRO_0000170822

Regions

Zinc finger235 – 26935FPG-type HAMAP-Rule MF_00103

Sites

Active site21Schiff-base intermediate with DNA
Active site31Proton donor Probable
Active site571Proton donor; for beta-elimination activity Probable
Active site2591Proton donor; for delta-elimination activity Probable
Binding site901DNA
Binding site1091DNA
Binding site1501DNA

Experimental info

Mutagenesis31E → Q: Strong decrease of glycosylase activity; slight decrease of AP lyase activity. Ref.9
Mutagenesis61E → Q: Decrease of glycosylase activity; no effect on AP lyase activity. Ref.9
Mutagenesis901H → A: Increase of substrate affinity and decrease of activity. Ref.11
Mutagenesis1071D → N: No effect on glycosylase and AP lyase activity. Ref.9
Mutagenesis1091R → A: Over 100-fold decrease of activity. Ref.11
Mutagenesis1101R → A: Over 100-fold increase of substrate affinity and decrease of activity. Ref.11
Mutagenesis1321E → Q: Decrease of glycosylase activity; slight decrease of AP lyase activity. Ref.9
Mutagenesis1601D → N: No effect on glycosylase and AP lyase activity. Ref.9
Mutagenesis1741E → Q: Strong decrease of glycosylase activity; slight decrease of AP lyase activity. Ref.9
Mutagenesis2181K → T: Slight increase of substrate affinity and decrease of activity. Ref.11

Secondary structure

.................................................... 269
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05523 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 01826F7E0E4686EC

FASTA26930,290
        10         20         30         40         50         60 
MPELPEVETS RRGIEPHLVG ATILHAVVRN GRLRWPVSEE IYRLSDQPVL SVQRRAKYLL 

        70         80         90        100        110        120 
LELPEGWIII HLGMSGSLRI LPEELPPEKH DHVDLVMSNG KVLRYTDPRR FGAWLWTKEL 

       130        140        150        160        170        180 
EGHNVLTHLG PEPLSDDFNG EYLHQKCAKK KTAIKPWLMD NKLVVGVGNI YASESLFAAG 

       190        200        210        220        230        240 
IHPDRLASSL SLAECELLAR VIKAVLLRSI EQGGTTLKDF LQSDGKPGYF AQELQVYGRK 

       250        260 
GEPCRVCGTP IVATKHAQRA TFYCRQCQK 

« Hide

References

« Hide 'large scale' references
[1]"Formamidopyrimidine-DNA glycosylase of Escherichia coli: cloning and sequencing of the fpg structural gene and overproduction of the protein."
Boiteux S., O'Connor T.R., Laval J.
EMBO J. 6:3177-3183(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Analysis of the Escherichia coli genome. V. DNA sequence of the region from 76.0 to 81.5 minutes."
Sofia H.J., Burland V., Daniels D.L., Plunkett G. III, Blattner F.R.
Nucleic Acids Res. 22:2576-2586(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[3]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[4]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]"DNA sequence and analysis of 136 kilobases of the Escherichia coli genome: organizational symmetry around the origin of replication."
Burland V.D., Plunkett G. III, Daniels D.L., Blattner F.R.
Genomics 16:551-561(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 1-182.
Strain: K12 / MG1655 / ATCC 47076.
[6]"A gene coding for 3-deoxy-D-manno-octulosonic-acid transferase in Escherichia coli. Identification, mapping, cloning, and sequencing."
Clementz T., Raetz C.R.H.
J. Biol. Chem. 266:9687-9696(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 181-269.
Strain: K12.
[7]"Homogeneous Escherichia coli FPG protein. A DNA glycosylase which excises imidazole ring-opened purines and nicks DNA at apurinic/apyrimidinic sites."
Boiteux S., O'Connor T.R., Lederer F., Gouyette A., Laval J.
J. Biol. Chem. 265:3916-3922(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-24, FUNCTION, SUBUNIT, COFACTOR.
[8]"Fpg protein of Escherichia coli is a zinc finger protein whose cysteine residues have a structural and/or functional role."
O'Connor T.E., Graves R.J., de Murcia G., Castaing B., Laval J.
J. Biol. Chem. 268:9063-9070(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[9]"Involvement of phylogenetically conserved acidic amino acid residues in catalysis by an oxidative DNA damage enzyme formamidopyrimidine glycosylase."
Lavrukhin O.V., Lloyd R.S.
Biochemistry 39:15266-15271(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-3; GLU-6; ASP-107; GLU-132; ASP-160 AND GLU-174.
[10]"The oxidative DNA glycosylases of Mycobacterium tuberculosis exhibit different substrate preferences from their Escherichia coli counterparts."
Guo Y., Bandaru V., Jaruga P., Zhao X., Burrows C.J., Iwai S., Dizdaroglu M., Bond J.P., Wallace S.S.
DNA Repair 9:177-190(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBSTRATES.
[11]"Substrate discrimination by formamidopyrimidine-DNA glycosylase: a mutational analysis."
Zaika E.I., Perlow R.A., Matz E., Broyde S., Gilboa R., Grollman A.P., Zharkov D.O.
J. Biol. Chem. 279:4849-4861(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HIS-90; ARG-109; ARG-110 AND LYS-218.
[12]"Structure of formamidopyrimidine-DNA glycosylase covalently complexed to DNA."
Gilboa R., Zharkov D.O., Golan G., Fernandes A.S., Gerchman S.E., Matz E., Kycia J.H., Grollman A.P., Shoham G.
J. Biol. Chem. 277:19811-19816(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-269 IN COMPLEX WITH DNA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M86305 Genomic DNA. Translation: AAA03747.1.
X06036 Genomic DNA. Translation: CAA29431.1.
L10328 Genomic DNA. Translation: AAA61988.1.
U00039 Genomic DNA. Translation: AAB18612.1.
U00096 Genomic DNA. Translation: AAC76659.1.
AP009048 Genomic DNA. Translation: BAE77657.1.
M60670 Genomic DNA. Translation: AAA24045.1.
PIRDGECFP. A30254.
RefSeqNP_418092.1. NC_000913.3.
YP_491798.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1K82X-ray2.10A/B/C/D2-269[»]
ProteinModelPortalP05523.
SMRP05523. Positions 2-269.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-10286N.
IntActP05523. 12 interactions.
STRING511145.b3635.

Proteomic databases

PaxDbP05523.
PRIDEP05523.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC76659; AAC76659; b3635.
BAE77657; BAE77657; BAE77657.
GeneID12933569.
946765.
KEGGecj:Y75_p3539.
eco:b3635.
PATRIC32122757. VBIEscCol129921_3755.

Organism-specific databases

EchoBASEEB0325.
EcoGeneEG10329. mutM.

Phylogenomic databases

eggNOGCOG0266.
HOGENOMHOG000020881.
KOK10563.
OMAGWIIVHL.
OrthoDBEOG6QP131.
PhylomeDBP05523.
ProtClustDBPRK01103.

Enzyme and pathway databases

BioCycEcoCyc:EG10329-MONOMER.
ECOL316407:JW3610-MONOMER.
MetaCyc:EG10329-MONOMER.

Gene expression databases

GenevestigatorP05523.

Family and domain databases

HAMAPMF_00103. Fapy_DNA_glycosyl.
InterProIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR015887. DNA_glyclase_Znf_dom_DNA_BS.
IPR000191. DNA_glycosylase/AP_lyase.
IPR012319. DNA_glycosylase/AP_lyase_cat.
IPR020629. Formamido-pyr_DNA_Glyclase.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
IPR010663. Znf_DNA_glyclase/IsotRNA_synth.
[Graphical view]
PfamPF01149. Fapy_DNA_glyco. 1 hit.
PF06831. H2TH. 1 hit.
PF06827. zf-FPG_IleRS. 1 hit.
[Graphical view]
SMARTSM00898. Fapy_DNA_glyco. 1 hit.
[Graphical view]
SUPFAMSSF46946. SSF46946. 1 hit.
SSF81624. SSF81624. 1 hit.
TIGRFAMsTIGR00577. fpg. 1 hit.
PROSITEPS51068. FPG_CAT. 1 hit.
PS01242. ZF_FPG_1. 1 hit.
PS51066. ZF_FPG_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP05523.
PROP05523.

Entry information

Entry nameFPG_ECOLI
AccessionPrimary (citable) accession number: P05523
Secondary accession number(s): Q2M7U9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene