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Protein

Flap endonuclease 1

Gene

FEN1

Organism
Homo sapiens (Human)
Status
Unreviewed-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 annotationSAAS 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

Complete GO annotation...

Keywords - Molecular functioni

EndonucleaseUniRule annotationImported, ExonucleaseUniRule annotation, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA repairUniRule annotation, DNA replicationUniRule annotation

Keywords - Ligandi

MagnesiumUniRule annotation, Metal-bindingUniRule annotation

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 annotationImported
ORF Names:hCG_40848Imported
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Subcellular locationi

  • Mitochondrion SAAS annotation
  • 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

MitochondrionUniRule annotationSAAS annotation, NucleusUniRule annotationSAAS annotation

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28090.

PTM / Processingi

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei100 – 1001Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei104 – 1041Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei187 – 1871Phosphoserine; by CDK2UniRule annotation
Modified residuei192 – 1921Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei354 – 3541N6-acetyllysineUniRule annotation
Modified residuei375 – 3751N6-acetyllysineUniRule annotation
Modified residuei377 – 3771N6-acetyllysineUniRule annotation
Modified residuei380 – 3801N6-acetyllysineUniRule annotation

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

Keywords - PTMi

AcetylationUniRule annotation, MethylationUniRule annotation, PhosphoproteinUniRule annotation

Proteomic databases

MaxQBiQ6FHX6.

Expressioni

Gene expression databases

BgeeiENSG00000168496.

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. The C-terminal domain binds EP300. Can bind simultaneously to both PCNA and EP300. Interacts with DDX11.UniRule annotation

Protein-protein interaction databases

STRINGi9606.ENSP00000305480.

Structurei

3D structure databases

SMRiQ6FHX6. Positions 2-336.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 107107XPGNInterPro annotationAdd
BLAST
Domaini146 – 21873XPGIInterPro annotationAdd
BLAST

Region

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

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili97 – 13640Sequence analysisAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Coiled coilSequence analysis

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
HOVERGENiHBG000844.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG091G0C0E.
PhylomeDBiQ6FHX6.

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.

Q6FHX6-1 [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 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:May 10, 2005 - v1
Checksum:i5154F2F6E57592C5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT019524 mRNA. Translation: AAV38331.1.
AK312761 mRNA. Translation: BAG35627.1.
CR536562 mRNA. Translation: CAG38799.1.
CH471076 Genomic DNA. Translation: EAW73972.1.
RefSeqiNP_004102.1. NM_004111.5.
UniGeneiHs.409065.

Genome annotation databases

GeneIDi2237.
KEGGihsa:2237.
UCSCiuc001nsg.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT019524 mRNA. Translation: AAV38331.1.
AK312761 mRNA. Translation: BAG35627.1.
CR536562 mRNA. Translation: CAG38799.1.
CH471076 Genomic DNA. Translation: EAW73972.1.
RefSeqiNP_004102.1. NM_004111.5.
UniGeneiHs.409065.

3D structure databases

SMRiQ6FHX6. Positions 2-336.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000305480.

Proteomic databases

MaxQBiQ6FHX6.

Protocols and materials databases

DNASUi2237.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi2237.
KEGGihsa:2237.
UCSCiuc001nsg.4. human.

Organism-specific databases

CTDi2237.
PharmGKBiPA28090.

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
HOVERGENiHBG000844.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG091G0C0E.
PhylomeDBiQ6FHX6.

Miscellaneous databases

ChiTaRSiFEN1. human.
GenomeRNAii2237.

Gene expression databases

BgeeiENSG00000168496.

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 nameiQ6FHX6_HUMAN
AccessioniPrimary (citable) accession number: Q6FHX6
Entry historyi
Integrated into UniProtKB/TrEMBL: May 10, 2005
Last sequence update: May 10, 2005
Last modified: September 7, 2016
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiUnreviewed (UniProtKB/TrEMBL)
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.

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.