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Protein

Flap endonuclease 1

Gene

fen1

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 4 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 annotation

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi34 – 341Magnesium 1UniRule annotation
Binding sitei47 – 471DNA substrateUniRule annotation
Binding sitei70 – 701DNA substrateUniRule annotation
Metal bindingi86 – 861Magnesium 1UniRule annotation
Metal bindingi158 – 1581Magnesium 1UniRule annotation
Binding sitei158 – 1581DNA substrateUniRule annotation
Metal bindingi160 – 1601Magnesium 1UniRule annotation
Metal bindingi179 – 1791Magnesium 2UniRule annotation
Metal bindingi181 – 1811Magnesium 2UniRule annotation
Binding sitei231 – 2311DNA substrateUniRule annotation
Metal bindingi233 – 2331Magnesium 2UniRule annotation
Binding sitei233 – 2331DNA substrateUniRule annotation

GO - Molecular functioni

GO - Biological processi

  • base-excision repair Source: UniProtKB-HAMAP
  • DNA replication, removal of RNA primer Source: UniProtKB-HAMAP
  • retina development in camera-type eye Source: ZFIN
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-DRE-110362. POLB-Dependent Long Patch Base Excision Repair.
R-DRE-174437. Removal of the Flap Intermediate from the C-strand.
R-DRE-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-DRE-5685939. HDR through MMEJ (alt-NHEJ).
R-DRE-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:fen1
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Chromosome 24

Organism-specific databases

ZFINiZDB-GENE-031112-11. fen1.

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 380380Flap endonuclease 1PRO_0000403488Add
BLAST

Post-translational modificationi

Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma.UniRule annotation

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ6TNU4.
PRIDEiQ6TNU4.

Expressioni

Gene expression databases

BgeeiENSDARG00000011404.

Interactioni

Subunit structurei

Interacts with PCNA. 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.UniRule annotation

Protein-protein interaction databases

STRINGi7955.ENSDARP00000004016.

Structurei

3D structure databases

ProteinModelPortaliQ6TNU4.
SMRiQ6TNU4. Positions 2-356.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 104104N-domainAdd
BLAST
Regioni122 – 253132I-domainAdd
BLAST
Regioni336 – 3449Interaction with PCNAUniRule annotation

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOGENOMiHOG000193853.
HOVERGENiHBG000844.
InParanoidiQ6TNU4.
KOiK04799.
OMAiLCGDRQF.
OrthoDBiEOG091G0C0E.
PhylomeDBiQ6TNU4.
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]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q6TNU4-1) [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
MGIHGLAKLI ADHAPSAIKE HEIKSYFGRK IAIDASMCIY QFLIAVRQDG
60 70 80 90 100
NVLQNEDGET TSHLMGMFYR TIRMLESGIK PVYVFDGKPP QLKSGELEKR
110 120 130 140 150
VERRAEAEKL LAQAQEAGEQ ENIDKFSKRL VKVTKQHNEE CKKLLSLMGV
160 170 180 190 200
PYIEAPCEAE ASCAALVKAG KVYATATEDM DGLTFGTTVL LRHLTASEAK
210 220 230 240 250
KLPIQEFHFS RILQDMELTH QQFIDLCILL GCDYCGTIKG IGPKRAIDLI
260 270 280 290 300
KQHGSIEEIL ENIDPNKHPA PEDWLYKEAR GLFLEPEVVD GTSVDLKWNE
310 320 330 340 350
PDEDGLIQFM CAEKQFSEDR IRNGCKKITK SRQGSTQGRL DTFFTVTGSI
360 370 380
SSKRKEPETK GSAKKKQKTS ATPGKFKKGK
Length:380
Mass (Da):42,536
Last modified:July 5, 2004 - v1
Checksum:i6A8962C32067CBD2
GO
Isoform 2 (identifier: Q6TNU4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     223-380: FIDLCILLGC...ATPGKFKKGK → AVDTSVGQAS...GQTSYLSVAL

Show »
Length:330
Mass (Da):36,127
Checksum:i82CB6FD56790B8AC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti181 – 1811D → A in AAT68162 (PubMed:15256591).Curated
Sequence conflicti269 – 2691P → R in AAT68162 (PubMed:15256591).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei223 – 380158FIDLC…FKKGK → AVDTSVGQASSQQLVLTSQS ISQSNNQQPVHGSSVFTAKP SGLTPLKPHKGRHQLGFMLP SSTSTLHTPSSSFVVQTPSQ IPVQDSYISGVQSASQKSGQ TSYLSVAL in isoform 2. 1 PublicationVSP_040394Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY391423 mRNA. Translation: AAQ91235.1.
AY648844 mRNA. Translation: AAT68162.1.
BC049413 mRNA. Translation: AAH49413.1.
BC071488 mRNA. Translation: AAH71488.1.
RefSeqiNP_942115.1. NM_198820.1. [Q6TNU4-2]
UniGeneiDr.75750.

Genome annotation databases

EnsembliENSDART00000024224; ENSDARP00000004016; ENSDARG00000011404. [Q6TNU4-1]
GeneIDi386707.
KEGGidre:386707.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY391423 mRNA. Translation: AAQ91235.1.
AY648844 mRNA. Translation: AAT68162.1.
BC049413 mRNA. Translation: AAH49413.1.
BC071488 mRNA. Translation: AAH71488.1.
RefSeqiNP_942115.1. NM_198820.1. [Q6TNU4-2]
UniGeneiDr.75750.

3D structure databases

ProteinModelPortaliQ6TNU4.
SMRiQ6TNU4. Positions 2-356.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi7955.ENSDARP00000004016.

Proteomic databases

PaxDbiQ6TNU4.
PRIDEiQ6TNU4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSDART00000024224; ENSDARP00000004016; ENSDARG00000011404. [Q6TNU4-1]
GeneIDi386707.
KEGGidre:386707.

Organism-specific databases

CTDi2237.
ZFINiZDB-GENE-031112-11. fen1.

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOGENOMiHOG000193853.
HOVERGENiHBG000844.
InParanoidiQ6TNU4.
KOiK04799.
OMAiLCGDRQF.
OrthoDBiEOG091G0C0E.
PhylomeDBiQ6TNU4.
TreeFamiTF105701.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ6TNU4.

Gene expression databases

BgeeiENSDARG00000011404.

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 nameiFEN1A_DANRE
AccessioniPrimary (citable) accession number: Q6TNU4
Secondary accession number(s): Q6DRB5, Q7ZWH1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2011
Last sequence update: July 5, 2004
Last modified: September 7, 2016
This is version 87 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.