P05523 (FPG_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	269 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	DNA damage DNA repair
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Glycosidase Hydrolase Lyase
Technical term	3D-structure Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	base-excision repair, AP site formation Inferred from direct assay Ref.7. Source: EcoCyc nucleotide-excision repair Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred by curator Ref.7. Source: EcoCyc
Molecular_function	damaged DNA binding Inferred from direct assay PubMed 8332499. Source: EcoCyc endonuclease activity Inferred from direct assay PubMed 1731864PubMed 2664776Ref.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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7

Chain

2 – 269

268

Formamidopyrimidine-DNA glycosylase HAMAP-Rule MF_00103

PRO_0000170822

Regions

Zinc finger

235 – 269

35

FPG-type HAMAP-Rule MF_00103

Sites

Active site

2

1

Schiff-base intermediate with DNA

Active site

3

1

Proton donor Probable

Active site

57

1

Proton donor; for beta-elimination activity Probable

Active site

259

1

Proton donor; for delta-elimination activity Probable

Binding site

90

1

DNA

Binding site

109

1

DNA

Binding site

150

1

DNA

Experimental info

Mutagenesis

3

1

E → Q: Strong decrease of glycosylase activity; slight decrease of AP lyase activity. Ref.9

Mutagenesis

6

1

E → Q: Decrease of glycosylase activity; no effect on AP lyase activity. Ref.9

Mutagenesis

90

1

H → A: Increase of substrate affinity and decrease of activity. Ref.11

Mutagenesis

107

1

D → N: No effect on glycosylase and AP lyase activity. Ref.9

Mutagenesis

109

1

R → A: Over 100-fold decrease of activity. Ref.11

Mutagenesis

110

1

R → A: Over 100-fold increase of substrate affinity and decrease of activity. Ref.11

Mutagenesis

132

1

E → Q: Decrease of glycosylase activity; slight decrease of AP lyase activity. Ref.9

Mutagenesis

160

1

D → N: No effect on glycosylase and AP lyase activity. Ref.9

Mutagenesis

174

1

E → Q: Strong decrease of glycosylase activity; slight decrease of AP lyase activity. Ref.9

Mutagenesis

218

1

K → T: Slight increase of substrate affinity and decrease of activity. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

269

Helix Strand Turn

Details...

Helix

4 – 18

15

Beta strand

22 – 29

8

Beta strand

32 – 36

5

Helix

39 – 43

5

Beta strand

46 – 49

4

Beta strand

51 – 55

5

Beta strand

58 – 62

5

Beta strand

67 – 71

5

Turn

73 – 75

3

Beta strand

77 – 84

8

Beta strand

93 – 97

5

Beta strand

102 – 106

5

Beta strand

113 – 118

6

Beta strand

120 – 123

4

Helix

124 – 126

3

Helix

140 – 147

8

Helix

154 – 158

5

Turn

161 – 163

3

Helix

169 – 179

11

Helix

187 – 189

3

Helix

192 – 211

20

Helix

231 – 233

3

Turn

245 – 247

3

Beta strand

252 – 256

5

Beta strand

259 – 263

5

Turn

265 – 267

3

Sequences

	Sequence		Length	Mass (Da)
	P05523 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 01826F7E0E4686EC	FASTA	269	30,290
	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

References

	« Hide 'large scale' referencesShow '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 277:1453-1474(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.

PIR

DGECFP. A30254.

RefSeq

NP_418092.1. NC_000913.2.
YP_491798.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K82	X-ray	2.10	A/B/C/D	2-269	[»]

ProteinModelPortal

P05523.

SMR

P05523. Positions 2-269.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-10286N.

IntAct

P05523. 7 interactions.

STRING

511145.b3635.

Proteomic databases

PaxDb

P05523.

PRIDE

P05523.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBESCT00000003434; EBESCP00000003434; EBESCG00000002818.
EBESCT00000003435; EBESCP00000003435; EBESCG00000002818.
EBESCT00000003436; EBESCP00000003436; EBESCG00000002818.
EBESCT00000003437; EBESCP00000003437; EBESCG00000002818.
EBESCT00000015059; EBESCP00000014350; EBESCG00000014119.

GeneID

12933569.
946765.

KEGG

ecj:Y75_p3539.
eco:b3635.

PATRIC

32122757. VBIEscCol129921_3755.

Organism-specific databases

EchoBASE

EB0325.

EcoGene

EG10329. mutM.

Phylogenomic databases

eggNOG

COG0266.

HOGENOM

HOG000020881.

KO

K10563.

OMA

VLRYNDP.

ProtClustDB

PRK01103.

Enzyme and pathway databases

BioCyc

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

Gene expression databases

Genevestigator

P05523.

Family and domain databases

HAMAP

MF_00103. Fapy-DNA_glycosyl.

InterPro

IPR015886. 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]

Pfam

PF01149. Fapy_DNA_glyco. 1 hit.
PF06831. H2TH. 1 hit.
PF06827. zf-FPG_IleRS. 1 hit.
[Graphical view]

SMART

SM00898. Fapy_DNA_glyco. 1 hit.
[Graphical view]

SUPFAM

SSF81624. Form_DNAglyc_cat. 1 hit.
SSF46946. Ribosomal_H2TH. 1 hit.

TIGRFAMs

TIGR00577. fpg. 1 hit.

PROSITE

PS51068. FPG_CAT. 1 hit.
PS01242. ZF_FPG_1. 1 hit.
PS51066. ZF_FPG_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P05523.

Entry information

Entry name

FPG_ECOLI

Accession

Primary (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:	May 1, 2013
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program