FEN1_CAEEL
ID FEN1_CAEEL Reviewed; 382 AA.
AC Q9N3T2;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Flap endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE Short=FEN-1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03140};
DE AltName: Full=Cell death-related nuclease 1;
DE AltName: Full=Flap structure-specific endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140};
GN Name=crn-1 {ECO:0000255|HAMAP-Rule:MF_03140}; ORFNames=Y47G6A.8;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12718884; DOI=10.1016/s1097-2765(03)00095-9;
RA Parrish J.Z., Xue D.;
RT "Functional genomic analysis of apoptotic DNA degradation in C. elegans.";
RL Mol. Cell 11:987-996(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CPS-6.
RX PubMed=12840007; DOI=10.1093/emboj/cdg320;
RA Parrish J.Z., Yang C., Shen B., Xue D.;
RT "CRN-1, a Caenorhabditis elegans FEN-1 homologue, cooperates with CPS-
RT 6/EndoG to promote apoptotic DNA degradation.";
RL EMBO J. 22:3451-3460(2003).
CC -!- FUNCTION: Structure-specific nuclease with 5'-flap endonuclease and 5'-
CC 3' exonuclease activities involved in DNA replication and repair.
CC During DNA replication, cleaves the 5'-overhanging flap structure that
CC is generated by displacement synthesis when DNA polymerase encounters
CC the 5'-end of a downstream Okazaki fragment. It enters the flap from
CC the 5'-end and then tracks to cleave the flap base, leaving a nick for
CC ligation. Also involved in the long patch base excision repair (LP-BER)
CC pathway, by cleaving within the apurinic/apyrimidinic (AP) site-
CC terminated flap. Acts as a genome stabilization factor that prevents
CC flaps from equilibrating into structures that lead to duplications and
CC deletions. Also possesses 5'-3' exonuclease activity on nicked or
CC gapped double-stranded DNA, and exhibits RNase H activity. Also
CC involved in replication and repair of rDNA and in repairing
CC mitochondrial DNA (By similarity). Can associate and cooperate with
CC cps-6 to promote stepwise DNA fragmentation, utilizing the endonuclease
CC activity of cps-6 and both of its own 5'-3' exonuclease activity and
CC gap-dependent endonuclease activity. May play a critical role in
CC switching the state of cells from DNA replication/repair to DNA
CC degradation during apoptosis. {ECO:0000255|HAMAP-Rule:MF_03140,
CC ECO:0000269|PubMed:12840007}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03140};
CC Note=Binds 2 magnesium ions per subunit. They probably participate in
CC the reaction catalyzed by the enzyme. May bind an additional third
CC magnesium ion after substrate binding. {ECO:0000255|HAMAP-
CC Rule:MF_03140};
CC -!- SUBUNIT: Interacts with PCNA. Three molecules of crn-1 bind to one PCNA
CC trimer with each molecule binding to one PCNA monomer. PCNA stimulates
CC the nuclease activity without altering cleavage specificity (By
CC similarity). Interacts with cps-6. {ECO:0000255|HAMAP-Rule:MF_03140,
CC ECO:0000269|PubMed:12840007}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000255|HAMAP-
CC Rule:MF_03140}. Nucleus, nucleoplasm {ECO:0000255|HAMAP-Rule:MF_03140}.
CC Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03140}. Note=Resides mostly in
CC the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
CC {ECO:0000255|HAMAP-Rule:MF_03140}.
CC -!- PTM: Phosphorylated. Phosphorylation upon DNA damage induces
CC relocalization to the nuclear plasma. {ECO:0000255|HAMAP-
CC Rule:MF_03140}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03140}.
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DR EMBL; AY303575; AAP57297.1; -; mRNA.
DR EMBL; FO081580; CCD72553.1; -; Genomic_DNA.
DR RefSeq; NP_491168.1; NM_058767.6.
DR AlphaFoldDB; Q9N3T2; -.
DR SMR; Q9N3T2; -.
DR BioGRID; 37393; 17.
DR DIP; DIP-26974N; -.
DR IntAct; Q9N3T2; 2.
DR MINT; Q9N3T2; -.
DR STRING; 6239.Y47G6A.8; -.
DR EPD; Q9N3T2; -.
DR PaxDb; Q9N3T2; -.
DR PeptideAtlas; Q9N3T2; -.
DR EnsemblMetazoa; Y47G6A.8.1; Y47G6A.8.1; WBGene00000794.
DR GeneID; 171917; -.
DR KEGG; cel:CELE_Y47G6A.8; -.
DR UCSC; Y47G6A.8; c. elegans.
DR CTD; 171917; -.
DR WormBase; Y47G6A.8; CE22109; WBGene00000794; crn-1.
DR eggNOG; KOG2519; Eukaryota.
DR GeneTree; ENSGT00940000155807; -.
DR HOGENOM; CLU_032444_2_0_1; -.
DR InParanoid; Q9N3T2; -.
DR OMA; GSQDYDS; -.
DR OrthoDB; 1094524at2759; -.
DR PhylomeDB; Q9N3T2; -.
DR Reactome; R-CEL-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-CEL-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-CEL-69166; Removal of the Flap Intermediate.
DR PRO; PR:Q9N3T2; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000794; Expressed in embryo and 4 other tissues.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IBA:GO_Central.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0048256; F:flap endonuclease activity; IDA:WormBase.
DR GO; GO:0000287; F:magnesium ion binding; IBA:GO_Central.
DR GO; GO:0030145; F:manganese ion binding; IBA:GO_Central.
DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IBA:GO_Central.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IDA:WormBase.
DR GO; GO:0006284; P:base-excision repair; IEA:UniProtKB-UniRule.
DR GO; GO:0006281; P:DNA repair; TAS:WormBase.
DR GO; GO:0006260; P:DNA replication; TAS:WormBase.
DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IEA:UniProtKB-UniRule.
DR HAMAP; MF_00614; Fen; 1.
DR InterPro; IPR036279; 5-3_exonuclease_C_sf.
DR InterPro; IPR023426; Flap_endonuc.
DR InterPro; IPR008918; HhH2.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR006086; XPG-I_dom.
DR InterPro; IPR006084; XPG/Rad2.
DR InterPro; IPR019974; XPG_CS.
DR InterPro; IPR006085; XPG_DNA_repair_N.
DR PANTHER; PTHR11081; PTHR11081; 1.
DR Pfam; PF00867; XPG_I; 1.
DR Pfam; PF00752; XPG_N; 1.
DR PRINTS; PR00853; XPGRADSUPER.
DR SMART; SM00279; HhH2; 1.
DR SMART; SM00484; XPGI; 1.
DR SMART; SM00485; XPGN; 1.
DR SUPFAM; SSF47807; SSF47807; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
DR PROSITE; PS00841; XPG_1; 1.
DR PROSITE; PS00842; XPG_2; 1.
PE 1: Evidence at protein level;
KW DNA damage; DNA repair; DNA replication; Endonuclease; Exonuclease;
KW Hydrolase; Magnesium; Metal-binding; Mitochondrion; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..382
FT /note="Flap endonuclease 1"
FT /id="PRO_0000403513"
FT REGION 1..104
FT /note="N-domain"
FT REGION 122..253
FT /note="I-domain"
FT REGION 336..344
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT REGION 358..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 47
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 70
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 86
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 158
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 160
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 179
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 181
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 231
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 233
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 233
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
SQ SEQUENCE 382 AA; 42549 MW; FDFE0BA0707321EB CRC64;
MGIKGLSQVI ADNAPSAIKV NEMKAFFGRT VAIDASMCLY QFLIAVRQDG SQLQSEDGET
TSHLMGMLNR TVRMFENGVK PVYVFDGKPP DMKGGELEKR SERRAEAEKA LTEAKEKGDV
KEAEKFERRL VKVTKQQNDE AKRLLGLMGI PVVEAPCEAE AQCAHLVKAG KVFGTVTEDM
DALTFGSTVL LRHFLAPVAK KIPIKEFNLS LALEEMKLSV EEFIDLCILL GCDYCGTIRG
VGPKKAVELI RQHKNIETIL ENIDQNKYPP PEDWPYKRAR ELFLNPEVTK PEEVELTWKE
ADVEGVIQFL CGEKNFNEER IRNALAKLKT SRKSGTQGRI DSFFGNSTKV TCVTAATKRK
AEEAEKAKKG AKKGGPPKKR AK
