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Protein

Flap endonuclease 1

Gene

FEN1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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.UniRule annotation3 Publications

Cofactori

Mg2+UniRule annotationNote: 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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi34Magnesium 1UniRule annotation1
Binding sitei47DNA substrateUniRule annotation1
Binding sitei70DNA substrateUniRule annotation1
Metal bindingi86Magnesium 1UniRule annotation1
Metal bindingi158Magnesium 1UniRule annotation1
Binding sitei158DNA substrateUniRule annotation1
Metal bindingi160Magnesium 1UniRule annotation1
Metal bindingi179Magnesium 2UniRule annotation1
Metal bindingi181Magnesium 2UniRule annotation1
Binding sitei231DNA substrateUniRule annotation1
Metal bindingi233Magnesium 2UniRule annotation1
Binding sitei233DNA substrateUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA repair, DNA replication

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-BTA-110362. POLB-Dependent Long Patch Base Excision Repair.
R-BTA-174437. Removal of the Flap Intermediate from the C-strand.
R-BTA-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-BTA-5685939. HDR through MMEJ (alt-NHEJ).
R-BTA-69166. Removal of the Flap Intermediate.

Names & Taxonomyi

Protein namesi
Recommended name:
Flap endonuclease 1UniRule annotation (EC:3.1.-.-UniRule annotation)
Short name:
FEN-1UniRule annotation
Alternative name(s):
Flap structure-specific endonuclease 1UniRule annotation
Gene namesi
Name:FEN1UniRule annotation
Synonyms:RTH-1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 29

Subcellular locationi

  • Nucleusnucleolus UniRule annotation
  • Nucleusnucleoplasm UniRule annotation
  • Mitochondrion UniRule annotation

  • Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002391141 – 380Flap endonuclease 1Add BLAST380

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei80N6-acetyllysineUniRule annotationBy similarity1
Modified residuei100Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei104Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei187Phosphoserine; by CDK2UniRule annotationBy similarity1
Modified residuei192Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei197PhosphoserineBy similarity1
Modified residuei255PhosphoserineBy similarity1
Modified residuei293PhosphoserineBy similarity1
Modified residuei335PhosphoserineBy similarity1
Modified residuei336PhosphothreonineBy similarity1
Modified residuei354N6-acetyllysineUniRule annotationBy similarity1
Modified residuei375N6-acetyllysineUniRule annotationBy similarity1
Modified residuei377N6-acetyllysineUniRule annotationBy similarity1
Modified residuei380N6-acetyllysineUniRule annotationBy similarity1

Post-translational modificationi

Acetylated by EP300. Acetylation inhibits both endonuclease and exonuclease activity. Acetylation also reduces DNA-binding activity but does not affect interaction with PCNA or EP300.UniRule annotation
Phosphorylation upon DNA damage induces relocalization to the nuclear plasma. Phosphorylation at Ser-187 by CDK2 occurs during late S-phase and results in dissociation from PCNA.UniRule annotation
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.UniRule annotation

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ58DH8.
PRIDEiQ58DH8.

Expressioni

Gene expression databases

BgeeiENSBTAG00000000064.

Interactioni

Subunit structurei

Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity. The C-terminal domain binds EP300; can bind simultaneously to both PCNA and EP300. Interacts with PCNA; can bind simultaneously to both PCNA and EP300. Interacts with DDX11; this interaction is direct and increases flap endonuclease activity of FEN1.UniRule annotationBy similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000000071.

Structurei

3D structure databases

ProteinModelPortaliQ58DH8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 104N-domainAdd BLAST104
Regioni122 – 253I-domainAdd BLAST132
Regioni336 – 344Interaction with PCNAUniRule annotation9

Sequence similaritiesi

Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOGENOMiHOG000193853.
HOVERGENiHBG000844.
InParanoidiQ58DH8.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG091G0C0E.
TreeFamiTF105701.

Family and domain databases

CDDicd09867. PIN_FEN1. 1 hit.
Gene3Di3.40.50.1010. 1 hit.
HAMAPiMF_00614. Fen. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR023426. Flap_endonuc.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
PANTHERiPTHR11081. PTHR11081. 1 hit.
PfamiPF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]
PRINTSiPR00853. XPGRADSUPER.
SMARTiSM00279. HhH2. 1 hit.
SM00484. XPGI. 1 hit.
SM00485. XPGN. 1 hit.
[Graphical view]
SUPFAMiSSF47807. SSF47807. 1 hit.
SSF88723. SSF88723. 1 hit.
PROSITEiPS00841. XPG_1. 1 hit.
PS00842. XPG_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q58DH8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG
60 70 80 90 100
DVLQNEEGET TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR
110 120 130 140 150
SERRAEAEKQ LQEAQAAGAE AEVEKFTKRL VKVTKQHNDE CKHLLSLMGI
160 170 180 190 200
PYLDAPSEAE ASCAALVKAG KVYAAATEDM DCLTFGSPVL MRHLTASEAK
210 220 230 240 250
KLPIQEFHLS RILQELGLNQ EQFVDLCILL GSDYCESIRG IGPKRAVDLI
260 270 280 290 300
QKHKSIEEIV RRLDPNKYPV PENWLHKEAQ QLFLEPEVLD PESVELKWSE
310 320 330 340 350
PNEEELIKFM CGEKQFSEER IRSGVRRLSK SRQGSTQGRL DDFFKVTGSL
360 370 380
SSAKRKEPEP KGAAKKKAKT GAAGKFKRGK
Length:380
Mass (Da):42,510
Last modified:April 26, 2005 - v1
Checksum:i5A358BF94175A71E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti247V → M in AAX46374 (PubMed:16305752).Curated1
Sequence conflicti247V → M in AAI05256 (Ref. 2) Curated1
Sequence conflicti304E → K in AAX46374 (PubMed:16305752).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT021527 mRNA. Translation: AAX46374.1.
BT021540 mRNA. Translation: AAX46387.1.
BT021619 mRNA. Translation: AAX46466.1.
BT021755 mRNA. Translation: AAX46602.1.
BC105255 mRNA. Translation: AAI05256.1.
RefSeqiNP_001030285.1. NM_001035113.1.
UniGeneiBt.10503.

Genome annotation databases

EnsembliENSBTAT00000000071; ENSBTAP00000000071; ENSBTAG00000000064.
GeneIDi616242.
KEGGibta:616242.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT021527 mRNA. Translation: AAX46374.1.
BT021540 mRNA. Translation: AAX46387.1.
BT021619 mRNA. Translation: AAX46466.1.
BT021755 mRNA. Translation: AAX46602.1.
BC105255 mRNA. Translation: AAI05256.1.
RefSeqiNP_001030285.1. NM_001035113.1.
UniGeneiBt.10503.

3D structure databases

ProteinModelPortaliQ58DH8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000000071.

Proteomic databases

PaxDbiQ58DH8.
PRIDEiQ58DH8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000000071; ENSBTAP00000000071; ENSBTAG00000000064.
GeneIDi616242.
KEGGibta:616242.

Organism-specific databases

CTDi2237.

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOGENOMiHOG000193853.
HOVERGENiHBG000844.
InParanoidiQ58DH8.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG091G0C0E.
TreeFamiTF105701.

Enzyme and pathway databases

ReactomeiR-BTA-110362. POLB-Dependent Long Patch Base Excision Repair.
R-BTA-174437. Removal of the Flap Intermediate from the C-strand.
R-BTA-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-BTA-5685939. HDR through MMEJ (alt-NHEJ).
R-BTA-69166. Removal of the Flap Intermediate.

Gene expression databases

BgeeiENSBTAG00000000064.

Family and domain databases

CDDicd09867. PIN_FEN1. 1 hit.
Gene3Di3.40.50.1010. 1 hit.
HAMAPiMF_00614. Fen. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR023426. Flap_endonuc.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
PANTHERiPTHR11081. PTHR11081. 1 hit.
PfamiPF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]
PRINTSiPR00853. XPGRADSUPER.
SMARTiSM00279. HhH2. 1 hit.
SM00484. XPGI. 1 hit.
SM00485. XPGN. 1 hit.
[Graphical view]
SUPFAMiSSF47807. SSF47807. 1 hit.
SSF88723. SSF88723. 1 hit.
PROSITEiPS00841. XPG_1. 1 hit.
PS00842. XPG_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFEN1_BOVIN
AccessioniPrimary (citable) accession number: Q58DH8
Secondary accession number(s): Q3MHF6, Q58DS0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: April 26, 2005
Last modified: November 30, 2016
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.