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UniProtKB - P39748 (FEN1_HUMAN)

Protein

Flap endonuclease 1

Gene

FEN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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 annotation6 Publications

Cofactori

Mg2+Note: 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi34Magnesium 11
Binding sitei47DNA substrate1
Binding sitei70DNA substrate1
Metal bindingi86Magnesium 11
Metal bindingi158Magnesium 11
Binding sitei158DNA substrate1
Metal bindingi160Magnesium 11
Metal bindingi179Magnesium 21
Metal bindingi181Magnesium 21
Binding sitei231DNA substrate1
Metal bindingi233Magnesium 21
Binding sitei233DNA substrate1

GO - Molecular functioni

  • 5'-3' exonuclease activity Source: UniProtKB
  • 5'-flap endonuclease activity Source: UniProtKB
  • damaged DNA binding Source: ProtInc
  • DNA binding Source: UniProtKB
  • double-stranded DNA binding Source: ProtInc
  • double-stranded DNA exodeoxyribonuclease activity Source: ProtInc
  • endonuclease activity Source: ProtInc
  • exonuclease activity Source: ProtInc
  • flap endonuclease activity Source: UniProtKB
  • magnesium ion binding Source: UniProtKB-UniRule
  • RNA-DNA hybrid ribonuclease activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionEndonuclease, Exonuclease, Hydrolase, Nuclease
Biological processDNA damage, DNA repair, DNA replication
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-110362 POLB-Dependent Long Patch Base Excision Repair
R-HSA-162594 Early Phase of HIV Life Cycle
R-HSA-174437 Removal of the Flap Intermediate from the C-strand
R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5685939 HDR through MMEJ (alt-NHEJ)
R-HSA-69166 Removal of the Flap Intermediate
SignaLinkiP39748
SIGNORiP39748

Names & Taxonomyi

Protein namesi
Recommended name:
Flap endonuclease 1UniRule annotation (EC:3.1.-.-UniRule annotation)
Short name:
FEN-1UniRule annotation
Alternative name(s):
DNase IV
Flap structure-specific endonuclease 1UniRule annotation
Maturation factor 1
Short name:
MF1
Short name:
hFEN-1
Gene namesi
Name:FEN1UniRule annotation
Synonyms:RAD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000168496.3
HGNCiHGNC:3650 FEN1
MIMi600393 gene
neXtProtiNX_P39748

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi29R → A: No significant effect on exonuclease activity or flap endonuclease activity. 1 Publication1
Mutagenesisi34D → A: Loss of flap endonuclease activity but substrate binding activity is retained. 1 Publication1
Mutagenesisi47R → A: Significantly reduced exonuclease activity and reduced substrate binding. The positions of the cleavage sites are also shifted. 1 Publication1
Mutagenesisi70R → A: Loss of exonuclease activity and reduced endonuclease activity. Reduced substrate binding. 1 Publication1
Mutagenesisi73R → A: No significant effect on exonuclease activity or flap endonuclease activity. 1 Publication1
Mutagenesisi80K → A: No significant effect on exonuclease activity or flap endonuclease activity. 1 Publication1
Mutagenesisi86D → A: Loss of flap endonuclease activity but substrate binding activity is retained. 1 Publication1
Mutagenesisi103R → A: No effect on flap endonuclease activity or substrate binding. 1 Publication1
Mutagenesisi158E → A: Loss of flap endonuclease activity and substrate binding. 1 Publication1
Mutagenesisi179D → A: No effect on flap endonuclease activity or substrate binding. 1 Publication1
Mutagenesisi181D → A: Loss of flap endonuclease activity but substrate binding activity is retained. 1 Publication1
Mutagenesisi187S → A: Fails to translocate from nucleoli to the nuclear plasma. 1 Publication1
Mutagenesisi187S → D: Diminishes nucleolar localization. 1 Publication1
Mutagenesisi192R → K: Impairs ability to localize to sites of DNA replication or repair. 1 Publication1
Mutagenesisi231G → A: Loss of flap endonuclease activity and substrate binding. 1 Publication1
Mutagenesisi233D → A: Loss of flap endonuclease activity and substrate binding. 1 Publication1

Organism-specific databases

DisGeNETi2237
OpenTargetsiENSG00000168496
PharmGKBiPA28090

Chemistry databases

ChEMBLiCHEMBL5027

Polymorphism and mutation databases

BioMutaiFEN1
DMDMi729475

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001540691 – 380Flap endonuclease 1Add BLAST380

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication1
Modified residuei80N6-acetyllysineCombined sources1
Modified residuei100Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication1
Modified residuei104Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication1
Modified residuei187Phosphoserine; by CDK2UniRule annotation1 Publication1
Modified residuei192Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication1
Modified residuei197PhosphoserineCombined sources1
Modified residuei255PhosphoserineCombined sources1
Modified residuei293PhosphoserineCombined sources1
Modified residuei335PhosphoserineCombined sources1
Modified residuei336PhosphothreonineCombined sources1
Modified residuei354N6-acetyllysineUniRule annotation1 Publication1
Modified residuei364PhosphothreonineCombined sources1
Modified residuei375N6-acetyllysineUniRule annotationCombined sources1 Publication1
Modified residuei377N6-acetyllysineUniRule annotation1 Publication1
Modified residuei380N6-acetyllysineUniRule annotation1 Publication1

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 annotation1 Publication
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 annotation1 Publication
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.UniRule annotation1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP39748
PaxDbiP39748
PeptideAtlasiP39748
PRIDEiP39748
ProteomicsDBi55319
TopDownProteomicsiP39748-1 [P39748-1]

PTM databases

iPTMnetiP39748
PhosphoSitePlusiP39748
SwissPalmiP39748

Expressioni

Gene expression databases

BgeeiENSG00000168496 Expressed in 219 organ(s), highest expression level in amniotic fluid
CleanExiHS_FEN1
ExpressionAtlasiP39748 baseline and differential
GenevisibleiP39748 HS

Organism-specific databases

HPAiCAB002262
HPA006748

Interactioni

Subunit structurei

Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer (PubMed:15616578). PCNA stimulates the nuclease activity without altering cleavage specificity (PubMed:15616578). The C-terminal domain binds EP300; can bind simultaneously to both PCNA and EP300 (PubMed:11430825). Interacts with PCNA; can bind simultaneously to both PCNA and EP300 (PubMed:9305916, PubMed:11430825). Interacts with DDX11; this interaction is direct and increases flap endonuclease activity of FEN1 (PubMed:18499658).UniRule annotation4 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi108528, 81 interactors
CORUMiP39748
DIPiDIP-24216N
ELMiP39748
IntActiP39748, 35 interactors
MINTiP39748
STRINGi9606.ENSP00000305480

Chemistry databases

BindingDBiP39748

Structurei

Secondary structure

1380
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP39748
SMRiP39748
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP39748

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 104N-domainAdd BLAST104
Regioni122 – 253I-domainAdd BLAST132
Regioni336 – 344Interaction with PCNA1 Publication9

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2519 Eukaryota
COG0258 LUCA
GeneTreeiENSGT00640000091478
HOGENOMiHOG000193853
HOVERGENiHBG000844
InParanoidiP39748
KOiK04799
OMAiGSQDYDS
OrthoDBiEOG091G0C0E
PhylomeDBiP39748
TreeFamiTF105701

Family and domain databases

CDDicd09867 PIN_FEN1, 1 hit
HAMAPiMF_00614 Fen, 1 hit
InterProiView protein in InterPro
IPR036279 5-3_exonuclease_C_sf
IPR023426 Flap_endonuc
IPR008918 HhH2
IPR029060 PIN-like_dom_sf
IPR006086 XPG-I_dom
IPR006084 XPG/Rad2
IPR019974 XPG_CS
IPR006085 XPG_DNA_repair_N
PANTHERiPTHR11081 PTHR11081, 1 hit
PfamiView protein in Pfam
PF00867 XPG_I, 1 hit
PF00752 XPG_N, 1 hit
PRINTSiPR00853 XPGRADSUPER
SMARTiView protein in SMART
SM00279 HhH2, 1 hit
SM00484 XPGI, 1 hit
SM00485 XPGN, 1 hit
SUPFAMiSSF47807 SSF47807, 1 hit
SSF88723 SSF88723, 1 hit
PROSITEiView protein in PROSITE
PS00841 XPG_1, 1 hit
PS00842 XPG_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P39748-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 LQQAQAAGAE QEVEKFTKRL 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 PENWLHKEAH QLFLEPEVLD PESVELKWSE 
       310        320        330        340        350
PNEEELIKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL 
       360        370        380
SSAKRKEPEP KGSTKKKAKT GAAGKFKRGK
Length:380
Mass (Da):42,593
Last modified:February 1, 1995 - v1
Checksum:i5154F2F6E57592C5
GO
Isoform FENMIT (identifier: P39748-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-64: Missing.

Note: No nuclease activity. Binds preferentially to RNA flap structures and R-loops.
Show »
Length:316
Mass (Da):35,673
Checksum:i7D5CA94548F0ED99
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H1Y3F5H1Y3_HUMAN
Flap endonuclease 1
FEN1
165Annotation score:
I3L3E9I3L3E9_HUMAN
Flap endonuclease 1
FEN1
154Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0475201 – 64Missing in isoform FENMIT. CuratedAdd BLAST64

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76771 mRNA Translation: CAA54166.1
L37374 mRNA Translation: AAA91331.1
AF523117 Genomic DNA Translation: AAM74238.1
AC004770 Genomic DNA Translation: AAC23394.1
BC000323 mRNA Translation: AAH00323.1
CCDSiCCDS8010.1 [P39748-1]
PIRiA56531
RefSeqiNP_004102.1, NM_004111.5 [P39748-1]
UniGeneiHs.409065

Genome annotation databases

EnsembliENST00000305885; ENSP00000305480; ENSG00000168496 [P39748-1]
GeneIDi2237
KEGGihsa:2237

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76771 mRNA Translation: CAA54166.1
L37374 mRNA Translation: AAA91331.1
AF523117 Genomic DNA Translation: AAM74238.1
AC004770 Genomic DNA Translation: AAC23394.1
BC000323 mRNA Translation: AAH00323.1
CCDSiCCDS8010.1 [P39748-1]
PIRiA56531
RefSeqiNP_004102.1, NM_004111.5 [P39748-1]
UniGeneiHs.409065

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U7BX-ray1.88B331-350[»]
1UL1X-ray2.90X/Y/Z2-380[»]
3Q8KX-ray2.20A2-336[»]
3Q8LX-ray2.32A2-336[»]
3Q8MX-ray2.60A/B2-336[»]
3UVUX-ray2.38B352-370[»]
5E0VX-ray2.07C/D335-350[»]
5FV7X-ray2.84A/B1-336[»]
5K97X-ray2.10A2-336[»]
5KSEX-ray2.10A2-336[»]
5UM9X-ray2.81A2-336[»]
ProteinModelPortaliP39748
SMRiP39748
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108528, 81 interactors
CORUMiP39748
DIPiDIP-24216N
ELMiP39748
IntActiP39748, 35 interactors
MINTiP39748
STRINGi9606.ENSP00000305480

Chemistry databases

BindingDBiP39748
ChEMBLiCHEMBL5027

PTM databases

iPTMnetiP39748
PhosphoSitePlusiP39748
SwissPalmiP39748

Polymorphism and mutation databases

BioMutaiFEN1
DMDMi729475

Proteomic databases

EPDiP39748
PaxDbiP39748
PeptideAtlasiP39748
PRIDEiP39748
ProteomicsDBi55319
TopDownProteomicsiP39748-1 [P39748-1]

Protocols and materials databases

DNASUi2237
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305885; ENSP00000305480; ENSG00000168496 [P39748-1]
GeneIDi2237
KEGGihsa:2237

Organism-specific databases

CTDi2237
DisGeNETi2237
EuPathDBiHostDB:ENSG00000168496.3
GeneCardsiFEN1
HGNCiHGNC:3650 FEN1
HPAiCAB002262
HPA006748
MIMi600393 gene
neXtProtiNX_P39748
OpenTargetsiENSG00000168496
PharmGKBiPA28090
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2519 Eukaryota
COG0258 LUCA
GeneTreeiENSGT00640000091478
HOGENOMiHOG000193853
HOVERGENiHBG000844
InParanoidiP39748
KOiK04799
OMAiGSQDYDS
OrthoDBiEOG091G0C0E
PhylomeDBiP39748
TreeFamiTF105701

Enzyme and pathway databases

ReactomeiR-HSA-110362 POLB-Dependent Long Patch Base Excision Repair
R-HSA-162594 Early Phase of HIV Life Cycle
R-HSA-174437 Removal of the Flap Intermediate from the C-strand
R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5685939 HDR through MMEJ (alt-NHEJ)
R-HSA-69166 Removal of the Flap Intermediate
SignaLinkiP39748
SIGNORiP39748

Miscellaneous databases

ChiTaRSiFEN1 human
EvolutionaryTraceiP39748
GeneWikiiFlap_structure-specific_endonuclease_1
GenomeRNAii2237
PROiPR:P39748
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168496 Expressed in 219 organ(s), highest expression level in amniotic fluid
CleanExiHS_FEN1
ExpressionAtlasiP39748 baseline and differential
GenevisibleiP39748 HS

Family and domain databases

CDDicd09867 PIN_FEN1, 1 hit
HAMAPiMF_00614 Fen, 1 hit
InterProiView protein in InterPro
IPR036279 5-3_exonuclease_C_sf
IPR023426 Flap_endonuc
IPR008918 HhH2
IPR029060 PIN-like_dom_sf
IPR006086 XPG-I_dom
IPR006084 XPG/Rad2
IPR019974 XPG_CS
IPR006085 XPG_DNA_repair_N
PANTHERiPTHR11081 PTHR11081, 1 hit
PfamiView protein in Pfam
PF00867 XPG_I, 1 hit
PF00752 XPG_N, 1 hit
PRINTSiPR00853 XPGRADSUPER
SMARTiView protein in SMART
SM00279 HhH2, 1 hit
SM00484 XPGI, 1 hit
SM00485 XPGN, 1 hit
SUPFAMiSSF47807 SSF47807, 1 hit
SSF88723 SSF88723, 1 hit
PROSITEiView protein in PROSITE
PS00841 XPG_1, 1 hit
PS00842 XPG_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFEN1_HUMAN
AccessioniPrimary (citable) accession number: P39748
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: October 10, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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