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UniProtKB - Q6FHX6 (Q6FHX6_HUMAN)

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Protein

Flap endonuclease 1

Gene

FEN1

Organism
Homo sapiens (Human)
Status
Unreviewed-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 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)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

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionEndonucleaseUniRule annotationImported, ExonucleaseUniRule annotation, Hydrolase, Nuclease
Biological processDNA damage, DNA repairUniRule annotation, DNA replicationUniRule annotation
LigandMagnesiumUniRule 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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Subcellular locationi

  • Mitochondrion SAAS annotation
  • Nucleus › nucleolus UniRule annotation
  • Nucleus › nucleoplasm 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)DescriptionActionsGraphical viewLength
Modified residuei19Symmetric dimethylarginine; by PRMT5UniRule annotation1
Modified residuei100Symmetric dimethylarginine; by PRMT5UniRule annotation1
Modified residuei104Symmetric dimethylarginine; by PRMT5UniRule annotation1
Modified residuei187Phosphoserine; by CDK2UniRule annotation1
Modified residuei192Symmetric dimethylarginine; by PRMT5UniRule annotation1

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

MethylationUniRule annotation, PhosphoproteinUniRule annotation

Proteomic databases

MaxQBiQ6FHX6.

Expressioni

Gene expression databases

BgeeiENSG00000168496.
ExpressionAtlasiQ6FHX6. baseline and differential.

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

Structurei

3D structure databases

SMRiQ6FHX6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 107XPGNInterPro annotationAdd BLAST107
Domaini146 – 218XPGIInterPro annotationAdd BLAST73

Region

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

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili97 – 136Sequence analysisAdd BLAST40

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.

Family and domain databases

CDDicd09867. PIN_FEN1. 1 hit.
Gene3Di3.40.50.1010. 1 hit.
HAMAPiMF_00614. Fen. 1 hit.
InterProiView protein in InterPro
IPR020045. 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.
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.

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.

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.

Entry informationi

Entry nameiQ6FHX6_HUMAN
AccessioniPrimary (citable) accession number: Q6FHX6
Entry historyiIntegrated into UniProtKB/TrEMBL: May 10, 2005
Last sequence update: May 10, 2005
Last modified: July 5, 2017
This is version 116 of the entry and version 1 of the sequence. See 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.