UniProtKB - Q6FHX6 (Q6FHX6_HUMAN)
Flap endonuclease 1
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 structures 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 annotationARBA annotationCofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | 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
GO - Biological processi
- base-excision repair Source: UniProtKB-UniRule
- DNA replication, removal of RNA primer Source: UniProtKB-UniRule
- memory Source: Ensembl
Keywordsi
Molecular function | EndonucleaseUniRule annotationARBA annotation, ExonucleaseUniRule annotationARBA annotation, Hydrolase, Nuclease |
Biological process | DNA damage, DNA repairUniRule annotationARBA annotation, DNA replicationUniRule annotationARBA annotation |
Ligand | MagnesiumUniRule annotationARBA annotation, Metal-bindingUniRule annotationARBA 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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Organism-specific databases
VEuPathDBi | HostDB:ENSG00000168496 |
Subcellular locationi
Nucleus
- nucleolus UniRule annotation
- nucleoplasm UniRule annotation
Mitochondrion
- Mitochondrion UniRule annotation
Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.UniRule annotation
Mitochondrion
- mitochondrion Source: UniProtKB-SubCell
Nucleus
- nucleolus Source: HPA
- nucleoplasm Source: HPA
Keywords - Cellular componenti
MitochondrionUniRule annotation, NucleusUniRule annotationPTM / Processingi
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | 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
Keywords - PTMi
MethylationUniRule annotation, PhosphoproteinUniRule annotationARBA annotationExpressioni
Gene expression databases
Bgeei | ENSG00000168496, Expressed in amniotic fluid and 232 other tissues |
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 annotationProtein-protein interaction databases
IntActi | Q6FHX6, 1 interactor |
Structurei
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 | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 104 | N-domainUniRule annotationAdd BLAST | 104 | |
Regioni | 122 – 253 | I-domainUniRule annotationAdd BLAST | 132 | |
Regioni | 327 – 380 | DisorderedSequence analysisAdd BLAST | 54 | |
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 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 328 – 342 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 352 – 366 | Basic and acidic residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Keywords - Domaini
Coiled coilSequence analysisPhylogenomic databases
HOGENOMi | CLU_032444_2_0_1 |
OMAi | GSQDYDS |
OrthoDBi | 1094524at2759 |
Family and domain databases
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 |
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 |
i Sequence
Sequence statusi: Complete.
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
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 |
RefSeqi | NP_004102.1, NM_004111.5 |
Genome annotation databases
GeneIDi | 2237 |
KEGGi | hsa:2237 |
MANE-Selecti | ENST00000305885.3; ENSP00000305480.2; NM_004111.6; NP_004102.1 |
UCSCi | uc001nsg.4, human |
Similar proteinsi
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 |
RefSeqi | NP_004102.1, NM_004111.5 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
IntActi | Q6FHX6, 1 interactor |
Protocols and materials databases
Antibodypediai | 1878, 577 antibodies from 39 providers |
DNASUi | 2237 |
Genome annotation databases
GeneIDi | 2237 |
KEGGi | hsa:2237 |
MANE-Selecti | ENST00000305885.3; ENSP00000305480.2; NM_004111.6; NP_004102.1 |
UCSCi | uc001nsg.4, human |
Organism-specific databases
CTDi | 2237 |
PharmGKBi | PA28090 |
VEuPathDBi | HostDB:ENSG00000168496 |
Phylogenomic databases
HOGENOMi | CLU_032444_2_0_1 |
OMAi | GSQDYDS |
OrthoDBi | 1094524at2759 |
Miscellaneous databases
BioGRID-ORCSi | 2237, 517 hits in 1085 CRISPR screens |
ChiTaRSi | FEN1, human |
GenomeRNAii | 2237 |
Gene expression databases
Bgeei | ENSG00000168496, Expressed in amniotic fluid and 232 other tissues |
Family and domain databases
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 |
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 |
MobiDBi | 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: | May 25, 2022 | |
This is version 149 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. |