FEN1

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 key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	34	Magnesium 1UniRule annotation	1
Binding siteⁱ	47	DNA substrateUniRule annotation	1
Binding siteⁱ	70	DNA substrateUniRule annotation	1
Metal bindingⁱ	86	Magnesium 1UniRule annotation	1
Metal bindingⁱ	158	Magnesium 1UniRule annotation	1
Binding siteⁱ	158	DNA substrateUniRule annotation	1
Metal bindingⁱ	160	Magnesium 1UniRule annotation	1
Metal bindingⁱ	179	Magnesium 2UniRule annotation	1
Metal bindingⁱ	181	Magnesium 2UniRule annotation	1
Binding siteⁱ	231	DNA substrateUniRule annotation	1
Metal bindingⁱ	233	Magnesium 2UniRule annotation	1
Binding siteⁱ	233	DNA substrateUniRule annotation	1

GO - Molecular functionⁱ

5'-3' exonuclease activity Source: UniProtKB-UniRule
5'-flap endonuclease activity Source: UniProtKB-UniRule
DNA binding Source: UniProtKB-UniRule
magnesium ion binding Source: UniProtKB-UniRule

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

base-excision repair Source: UniProtKB-UniRule
DNA replication, removal of RNA primer Source: UniProtKB-UniRule
memory Source: Ensembl

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	EndonucleaseUniRule annotationImported, ExonucleaseUniRule annotation, Hydrolase, Nuclease
Biological process	DNA damage, DNA repairUniRule annotation, DNA replicationUniRule annotation
Ligand	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
Organismⁱ	Homo sapiens (Human)Imported
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000168496.3.

EuPathDBⁱ

HostDB:ENSG00000168496.3.

Keywords - Cellular componentⁱ

MitochondrionUniRule annotationSAAS annotation, NucleusUniRule annotationSAAS annotation

Pathology & Biotechⁱ

Organism-specific databases

PharmGKBⁱ	PA28090.

PharmGKBⁱ

PA28090.

PTM / Processingⁱ

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	19	Symmetric dimethylarginine; by PRMT5UniRule annotation	1
Modified residueⁱ	100	Symmetric dimethylarginine; by PRMT5UniRule annotation	1
Modified residueⁱ	104	Symmetric dimethylarginine; by PRMT5UniRule annotation	1
Modified residueⁱ	187	Phosphoserine; by CDK2UniRule annotation	1
Modified residueⁱ	192	Symmetric dimethylarginine; by PRMT5UniRule annotation	1

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

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000168496.

Bgeeⁱ

ENSG00000168496.

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

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	1 – 107	XPGNInterPro annotationAdd BLAST		107
Domainⁱ	146 – 218	XPGIInterPro annotationAdd BLAST		73

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	1 – 104	N-domainUniRule annotationAdd BLAST	104
Regionⁱ	122 – 253	I-domainUniRule annotationAdd BLAST	132
Regionⁱ	336 – 344	Interaction with PCNAUniRule annotation	9

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	97 – 136	Sequence analysisAdd BLAST		40

Sequence similaritiesⁱ

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

Keywords - Domainⁱ

Coiled coilSequence analysis

Phylogenomic databases

eggNOGⁱ	KOG2519. Eukaryota. COG0258. LUCA.
HOVERGENⁱ	HBG000844.
KEGG Orthology (KO) More...KOⁱ	K04799.
OMAⁱ	GSQDYDS.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0C0E.

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd09867. PIN_FEN1. 1 hit.
HAMAPⁱ	MF_00614. Fen. 1 hit.
InterProⁱ	View 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.
PANTHERⁱ	PTHR11081. PTHR11081. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00867. XPG_I. 1 hit. PF00752. XPG_N. 1 hit.
PRINTSⁱ	PR00853. XPGRADSUPER.
SMARTⁱ	View protein in SMART SM00279. HhH2. 1 hit. SM00484. XPGI. 1 hit. SM00485. XPGN. 1 hit.
SUPFAMⁱ	SSF47807. SSF47807. 1 hit. SSF88723. SSF88723. 1 hit.
PROSITEⁱ	View protein in PROSITE PS00841. XPG_1. 1 hit. PS00842. XPG_2. 1 hit.

Sequenceⁱ

Sequence statusⁱ: Complete.

Q6FHX6-1 [UniParc]FASTA Add 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.
NCBI Reference Sequences More...RefSeqⁱ	NP_004102.1. NM_004111.5.
UniGeneⁱ	Hs.409065.

Genome annotation databases

GeneIDⁱ	2237.
KEGGⁱ	hsa:2237.
UCSC genome browser More...UCSCⁱ	uc001nsg.4. human.

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins	Organisms	Length	Cluster ID	Cluster name	Size
Q6FHX6	P39748 H2Q3U7 H2ND72 G3RA03 B4DWZ4 P39748-2 UPI00004E17FD	Homo sapiens (Human) Pan troglodytes (Chimpanzee) Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) Gorilla gorilla gorilla (Western lowland gorilla)	380	UniRef100_P39748	Cluster: Flap endonuclease 1	8

Protein	Similar proteins	Organisms	Length	Cluster ID	Cluster name	Size
Q6FHX6	P39748 H2Q3U7 H2ND72 G3RA03 B4DWZ4 P39748-2 UPI00004E17FD UPI00075FCDF6 UPI000A1BD99C UPI00042CADB7 +106	Homo sapiens (Human) Pan troglodytes (Chimpanzee) Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) Gorilla gorilla gorilla (Western lowland gorilla) Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey) Odocoileus virginianus texanus Bubalus bubalis (Domestic water buffalo) Neotoma lepida (Desert woodrat) Acinonyx jubatus (Cheetah) Pteropus alecto (Black flying fox) And more	380	UniRef90_P39748	Cluster: Flap endonuclease 1	117

Protein	Similar proteins	Organisms	Length	Cluster ID	Cluster name	Size
Q6FHX6	P39748 H2Q3U7 H2ND72 G3RA03 B4DWZ4 P39748-2 UPI00004E17FD UPI00075FCDF6 UPI000A1BD99C UPI00042CADB7 +108	Homo sapiens (Human) Pan troglodytes (Chimpanzee) Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) Gorilla gorilla gorilla (Western lowland gorilla) Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey) Odocoileus virginianus texanus Bubalus bubalis (Domestic water buffalo) Neotoma lepida (Desert woodrat) Acinonyx jubatus (Cheetah) Rousettus aegyptiacus (Egyptian rousette) (Egyptian fruit bat) And more	380	UniRef50_P39748	Cluster: Flap endonuclease 1	119

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.
NCBI Reference Sequences More...RefSeqⁱ	NP_004102.1. NM_004111.5.
UniGeneⁱ	Hs.409065.

3D structure databases

ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	2237.
Structural Biology Knowledgebase	Search...

Genome annotation databases

GeneIDⁱ	2237.
KEGGⁱ	hsa:2237.
UCSC genome browser More...UCSCⁱ	uc001nsg.4. human.

Organism-specific databases

CTDⁱ	2237.
EuPathDBⁱ	HostDB:ENSG00000168496.3.
PharmGKBⁱ	PA28090.

Phylogenomic databases

eggNOGⁱ	KOG2519. Eukaryota. COG0258. LUCA.
HOVERGENⁱ	HBG000844.
KEGG Orthology (KO) More...KOⁱ	K04799.
OMAⁱ	GSQDYDS.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0C0E.

Miscellaneous databases

ChiTaRSⁱ	FEN1. human.
GenomeRNAiⁱ	2237.

Gene expression databases

Bgeeⁱ	ENSG00000168496.

Bgeeⁱ

ENSG00000168496.

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd09867. PIN_FEN1. 1 hit.
HAMAPⁱ	MF_00614. Fen. 1 hit.
InterProⁱ	View 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.
PANTHERⁱ	PTHR11081. PTHR11081. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00867. XPG_I. 1 hit. PF00752. XPG_N. 1 hit.
PRINTSⁱ	PR00853. XPGRADSUPER.
SMARTⁱ	View protein in SMART SM00279. HhH2. 1 hit. SM00484. XPGI. 1 hit. SM00485. XPGN. 1 hit.
SUPFAMⁱ	SSF47807. SSF47807. 1 hit. SSF88723. SSF88723. 1 hit.
PROSITEⁱ	View protein in PROSITE PS00841. XPG_1. 1 hit. PS00842. XPG_2. 1 hit.
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	Q6FHX6_HUMAN
Accessionⁱ	Q6FHX6Primary (citable) accession number: Q6FHX6
Entry historyⁱ	Integrated into UniProtKB/TrEMBL:	May 10, 2005
	Last sequence update:	May 10, 2005
	Last modified:	March 28, 2018
	This is version 122 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Unreviewed (UniProtKB/TrEMBL)
Disclaimer	Any 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.

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UniProtKB - Q6FHX6 (Q6FHX6_HUMAN)

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Flap endonuclease 1

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Mitochondrion

Mitochondrion

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Amino acid modifications

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Coiled coil

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

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Sequence databases

3D structure databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Cross-referencesⁱ

Entry informationⁱ