Flap endonuclease 1 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

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P26793 (FEN1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 122. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Flap endonuclease 1
Short name=FEN-1
EC=3.1.-.-

Alternative name(s):
Flap structure-specific endonuclease 1
RAD2 homolog nuclease 1
Short name=RTH1 nuclease
Structure-specific endonuclease RAD27

Gene names

Name:	RAD27
Synonyms:	FEN1, RTH1
Ordered Locus Names:	YKL113C
ORF Names:	YKL510

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces ›

Protein attributes

Sequence length	382 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA. Ref.4 Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
Cofactor	Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding By similarity.
Subunit structure	Interacts with PCNA (POL30). Three molecules of RAD27 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity. Ref.7
Subcellular location	Nucleus › nucleolus. Nucleus › nucleoplasm. Mitochondrion. Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage. Ref.10 Ref.15
Post-translational modification	Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma By similarity. HAMAP-Rule MF_03140
Miscellaneous	Present with 6120 molecules/cell in log phase SD medium. HAMAP-Rule MF_03140
Sequence similarities	Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.

Ontologies

Keywords
Biological process	DNA damage DNA repair DNA replication
Cellular component	Mitochondrion Nucleus
Ligand	Magnesium Metal-binding
Molecular function	Endonuclease Exonuclease Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication, removal of RNA primer Inferred from direct assay Ref.12. Source: SGD base-excision repair, base-free sugar-phosphate removal Inferred from mutant phenotype PubMed 9927726. Source: SGD double-strand break repair via nonhomologous end joining Inferred from direct assay PubMed 15342630. Source: SGD gene conversion at mating-type locus, DNA repair synthesis Inferred from mutant phenotype PubMed 10025407. Source: SGD replicative cell aging Inferred from mutant phenotype PubMed 12024027. Source: SGD
Cellular_component	mitochondrion Inferred from direct assay Ref.15. Source: SGD nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.10 Ref.15. Source: SGD
Molecular_function	5'-3' exonuclease activity Inferred from direct assay Ref.4. Source: SGD 5'-flap endonuclease activity Inferred from direct assay Ref.8. Source: SGD DNA binding Inferred from electronic annotation. Source: HAMAP magnesium ion binding Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DNA2	P38859	3	EBI-14693,EBI-5973
POL30	P15873	4	EBI-14693,EBI-12993

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 382

382

Flap endonuclease 1 HAMAP-Rule MF_03140

PRO_0000154038

Regions

Region

1 – 105

105

N-domain HAMAP-Rule MF_03140

Region

120 – 251

132

I-domain HAMAP-Rule MF_03140

Region

339 – 347

Interaction with PCNA By similarity

Sites

Metal binding

Magnesium 1 By similarity

Metal binding

Magnesium 1 By similarity

Metal binding

156

Magnesium 1 By similarity

Metal binding

158

Magnesium 1 By similarity

Metal binding

177

Magnesium 2 By similarity

Metal binding

179

Magnesium 2 By similarity

Metal binding

231

Magnesium 2 By similarity

Binding site

DNA substrate By similarity

Binding site

DNA substrate By similarity

Binding site

156

DNA substrate By similarity

Binding site

229

DNA substrate By similarity

Binding site

231

DNA substrate By similarity

Experimental info

Mutagenesis

G → S: Deficient in double and single flap endonuclease cleavage and exonucleolytic cleavage. Ref.7 Ref.12

Mutagenesis

176

E → A: Deficient in exonuclease and gap endonuclease activities, but retains almost all of its flap endonuclease activity. Ref.7 Ref.13

Mutagenesis

240

G → D: Can only cleave double-flap structures with a 3' 1-nucleotide tail. Has no exonuclease activity. Ref.7 Ref.8

Mutagenesis

346 – 347

FF → GA: Reduces interaction with POL30 more than 100 fold. Ref.7

Sequences

Sequence

Length

Mass (Da)

Tools

P26793 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 1F54B08720121C8C
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FASTA

382

43,279

        10         20         30         40         50         60 
MGIKGLNAII SEHVPSAIRK SDIKSFFGRK VAIDASMSLY QFLIAVRQQD GGQLTNEAGE 

        70         80         90        100        110        120 
TTSHLMGMFY RTLRMIDNGI KPCYVFDGKP PDLKSHELTK RSSRRVETEK KLAEATTELE 

       130        140        150        160        170        180 
KMKQERRLVK VSKEHNEEAQ KLLGLMGIPY IIAPTEAEAQ CAELAKKGKV YAAASEDMDT 

       190        200        210        220        230        240 
LCYRTPFLLR HLTFSEAKKE PIHEIDTELV LRGLDLTIEQ FVDLCIMLGC DYCESIRGVG 

       250        260        270        280        290        300 
PVTALKLIKT HGSIEKIVEF IESGESNNTK WKIPEDWPYK QARMLFLDPE VIDGNEINLK 

       310        320        330        340        350        360 
WSPPKEKELI EYLCDDKKFS EERVKSGISR LKKGLKSGIQ GRLDGFFQVV PKTKEQLAAA 

       370        380 
AKRAQENKKL NKNKNKVTKG RR

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a 10.7 kb segment of yeast chromosome XI identifies the APN1 and the BAF1 loci and reveals one tRNA gene and several new open reading frames including homologs to RAD2 and kinases." Jacquier A., Legrain P., Dujon B. Yeast 8:121-132(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Complete DNA sequence of yeast chromosome XI." Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., Daignan-Fornier B., del Rey F., Dion C. Mewes H.-W. Nature 369:371-378(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Purification and characterization of the DNA polymerase alpha associated exonuclease: the RTH1 gene product." Zhu F.X., Biswas E.E., Biswas S.B. Biochemistry 36:5947-5954(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 284-298, FUNCTION, EXONUCLEASE AND RNASE H ACTIVITIES.
[5]	"Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair." Harrington J.J., Lieber M.R. Genes Dev. 8:1344-1355(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[6]	"Characterization of a mutant strain of Saccharomyces cerevisiae with a deletion of the RAD27 gene, a structural homolog of the RAD2 nucleotide excision repair gene." Reagan M.S., Pittenger C., Siede W., Friedberg E.C. J. Bacteriol. 177:364-371(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[7]	"Two modes of FEN1 binding to PCNA regulated by DNA." Gomes X.V., Burgers P.M. EMBO J. 19:3811-3821(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH POL30, MUTAGENESIS OF 346-PHE-PHE-347.
[8]	"Cleavage specificity of Saccharomyces cerevisiae flap endonuclease 1 suggests a double-flap structure as the cellular substrate." Kao H.I., Henricksen L.A., Liu Y., Bambara R.A. J. Biol. Chem. 277:14379-14389(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENDONUCLEASE ACTIVITY, SUBSTRATE SPECIFICITY, MUTAGENESIS OF GLY-240.
[9]	"Okazaki fragment maturation in yeast. I. Distribution of functions between FEN1 AND DNA2." Ayyagari R., Gomes X.V., Gordenin D.A., Burgers P.M. J. Biol. Chem. 278:1618-1625(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[11]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[12]	"Reconstituted Okazaki fragment processing indicates two pathways of primer removal." Rossi M.L., Bambara R.A. J. Biol. Chem. 281:26051-26061(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-67.
[13]	"Concerted action of exonuclease and Gap-dependent endonuclease activities of FEN-1 contributes to the resolution of triplet repeat sequences (CTG)n-and (GAA)n-derived secondary structures formed during maturation of Okazaki fragments." Singh P., Zheng L., Chavez V., Qiu J., Shen B. J. Biol. Chem. 282:3465-3477(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENDONUCLEASE AND EXONUCLEASE ACTIVITIES, MUTAGENESIS OF GLU-176.
[14]	"Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair." Guo Z., Qian L., Liu R., Dai H., Zhou M., Zheng L., Shen B. Mol. Cell. Biol. 28:4310-4319(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RDNA REPLICATION AND REPAIR.
[15]	"Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity." Kalifa L., Beutner G., Phadnis N., Sheu S.S., Sia E.A. DNA Repair 8:1242-1249(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MITOCHONDRIAL DNA REPAIR, SUBCELLULAR LOCATION.
[16]	"The transition of closely opposed lesions to double-strand breaks during long-patch base excision repair is prevented by the coordinated action of DNA polymerase delta and Rad27/Fen1." Ma W., Panduri V., Sterling J.F., Van Houten B., Gordenin D.A., Resnick M.A. Mol. Cell. Biol. 29:1212-1221(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA REPAIR.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S93804 Genomic DNA. Translation: AAB21998.1. Z28113 Genomic DNA. Translation: CAA81953.1. BK006944 Genomic DNA. Translation: DAA09045.1.
PIR	S22267.
RefSeq	NP_012809.1. NM_001179679.1.
3D structure databases
ProteinModelPortal	P26793.
SMR	P26793. Positions 2-333.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2325N.
IntAct	P26793. 3 interactions.
MINT	MINT-536469.
STRING	4932.YKL113C.
Proteomic databases
PaxDb	P26793.
PeptideAtlas	P26793.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YKL113C; YKL113C; YKL113C.
GeneID	853747.
KEGG	sce:YKL113C.
Organism-specific databases
CYGD	YKL113c.
SGD	S000001596. RAD27.
Phylogenomic databases
eggNOG	COG0258.
GeneTree	ENSGT00640000091478.
KO	K04799.
OMA	DYDSLLF.
OrthoDB	EOG41VPBP.
Gene expression databases
Genevestigator	P26793.
GermOnline	YKL113C. Saccharomyces cerevisiae.
Family and domain databases
HAMAP	MF_00614. Fen.
InterPro	IPR020045. 5-3_exonuclease_C. IPR023426. Flap_endonuc. IPR008918. HhH2. IPR006086. XPG-I_dom. IPR006084. XPG/Rad2. IPR019974. XPG_CS. IPR006085. XPG_DNA_repair_N. [Graphical view]
PANTHER	PTHR11081. PTHR11081. 1 hit.
Pfam	PF00867. XPG_I. 1 hit. PF00752. XPG_N. 1 hit. [Graphical view]
PRINTS	PR00853. XPGRADSUPER.
SMART	SM00279. HhH2. 1 hit. SM00484. XPGI. 1 hit. SM00485. XPGN. 1 hit. [Graphical view]
SUPFAM	SSF47807. 5_3_exo_C. 1 hit.
PROSITE	PS00841. XPG_1. 1 hit. PS00842. XPG_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	974807.

Entry information

Entry name

FEN1_YEAST

Accession

Primary (citable) accession number: P26793
Secondary accession number(s): D6VXH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	April 3, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program

Relevant documents

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

Yeast chromosome XI

Yeast (Saccharomyces cerevisiae) chromosome XI: entries and gene names

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents