Q8C5X6 (Q8C5X6_MOUSE) Unreviewed, UniProtKB/TrEMBL

Names and origin

Protein names

Recommended name:
Flap endonuclease 1 HAMAP-Rule MF_03140
Short name=FEN-1 HAMAP-Rule MF_03140
EC=3.1.-.- HAMAP-Rule MF_03140

Alternative name(s):
Flap structure-specific endonuclease 1 HAMAP-Rule MF_03140

Gene names

Name:	Fen1 MGI 102779
Synonyms:	FEN1 HAMAP-Rule MF_03140

Organism

Mus musculus (Mouse) EMBL BAC36544.1

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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 By similarity. HAMAP-Rule MF_03140
Cofactor	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 By similarity. HAMAP-Rule MF_03140
Subunit structure	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 By similarity. HAMAP-Rule MF_03140
Subcellular location	Nucleus › nucleolus. Nucleus › nucleoplasm. Mitochondrion. Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage By similarity. HAMAP-Rule MF_03140
Post-translational modification	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 By similarity. HAMAP-Rule MF_03140 Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA By similarity. HAMAP-Rule MF_03140 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 By similarity. HAMAP-Rule MF_03140
Sequence similarities	Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily. HAMAP-Rule MF_03140

Ontologies

Keywords
Biological process	DNA damage DNA repair HAMAP-Rule MF_03140 DNA replication HAMAP-Rule MF_03140
Cellular component	Mitochondrion SAAS SAAS020045 HAMAP-Rule MF_03140 Nucleus HAMAP-Rule MF_03140 SAAS SAAS020045
Ligand	Magnesium HAMAP-Rule MF_03140 Metal-binding HAMAP-Rule MF_03140
Molecular function	Endonuclease HAMAP-Rule MF_03140 Exonuclease HAMAP-Rule MF_03140 Hydrolase Nuclease
PTM	Acetylation HAMAP-Rule MF_03140 Methylation HAMAP-Rule MF_03140 Phosphoprotein HAMAP-Rule MF_03140 SAAS SAAS020045
Gene Ontology (GO)
Biological_process	DNA repair Inferred from mutant phenotype PubMed 12861020. Source: MGI DNA replication Inferred from mutant phenotype PubMed 12861020. Source: MGI DNA replication, removal of RNA primer Inferred from electronic annotation. Source: HAMAP base-excision repair Inferred from electronic annotation. Source: HAMAP memory Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Traceable author statement PubMed 12162748. Source: MGI
Molecular_function	5'-3' exonuclease activity Inferred from electronic annotation. Source: HAMAP 5'-flap endonuclease activity Inferred from electronic annotation. Source: HAMAP DNA binding Inferred from direct assay PubMed 12162748. Source: MGI exonuclease activity Inferred from direct assay PubMed 12162748. Source: MGI flap endonuclease activity Inferred from direct assay PubMed 12162748. Source: MGI magnesium ion binding Inferred from direct assay PubMed 12162748. Source: MGI manganese ion binding Inferred from direct assay PubMed 12162748. Source: MGI ribonuclease H activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Regions
	Region	1 – 104	104	N-domain By similarity HAMAP-Rule MF_03140
	Region	122 – 253	132	I-domain By similarity HAMAP-Rule MF_03140
	Region	336 – 344	9	Interaction with PCNA By similarity HAMAP-Rule MF_03140
Sites
	Metal binding	34	1	Magnesium 1 By similarity HAMAP-Rule MF_03140
	Metal binding	86	1	Magnesium 1 By similarity HAMAP-Rule MF_03140
	Metal binding	158	1	Magnesium 1 By similarity HAMAP-Rule MF_03140
	Metal binding	160	1	Magnesium 1 By similarity HAMAP-Rule MF_03140
	Metal binding	179	1	Magnesium 2 By similarity HAMAP-Rule MF_03140
	Metal binding	181	1	Magnesium 2 By similarity HAMAP-Rule MF_03140
	Metal binding	233	1	Magnesium 2 By similarity HAMAP-Rule MF_03140
	Binding site	47	1	DNA substrate By similarity HAMAP-Rule MF_03140
	Binding site	70	1	DNA substrate By similarity HAMAP-Rule MF_03140
	Binding site	158	1	DNA substrate By similarity HAMAP-Rule MF_03140
	Binding site	231	1	DNA substrate By similarity HAMAP-Rule MF_03140
	Binding site	233	1	DNA substrate By similarity HAMAP-Rule MF_03140
Amino acid modifications
	Modified residue	19	1	Symmetric dimethylarginine; by PRMT5 By similarity HAMAP-Rule MF_03140
	Modified residue	100	1	Symmetric dimethylarginine; by PRMT5 By similarity HAMAP-Rule MF_03140
	Modified residue	104	1	Symmetric dimethylarginine; by PRMT5 By similarity HAMAP-Rule MF_03140
	Modified residue	187	1	Phosphoserine; by CDK2 By similarity HAMAP-Rule MF_03140
	Modified residue	192	1	Symmetric dimethylarginine; by PRMT5 By similarity HAMAP-Rule MF_03140
	Modified residue	354	1	N6-acetyllysine By similarity HAMAP-Rule MF_03140
	Modified residue	375	1	N6-acetyllysine By similarity HAMAP-Rule MF_03140
	Modified residue	380	1	N6-acetyllysine By similarity HAMAP-Rule MF_03140

Sequences

	Sequence		Length	Mass (Da)
	Q8C5X6 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 00FB31520454032D	FASTA	411	45,820
	10 20 30 40 50 60 MGIHGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET 70 80 90 100 110 120 TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR SERRAEAEKQ LQQAQEAGME 130 140 150 160 170 180 EEVEKFTKRL VKVTKQHNDE CKHLLSLMGI PYLDAPSEAE ASCAALAKAG KVYAAATEDM 190 200 210 220 230 240 DCLTFGSPVL MRHLTASEAK KLPIQEFHLS RVLQELGLNQ EQFVDLCILL GSDYCESIRG 250 260 270 280 290 300 IGPKRAVDLI QKHKSIEEIV RRLDPSKYPV PENWLHKEAQ QLFLEPEVLD PESVELKWSE 310 320 330 340 350 360 PNEEELVKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL SSAKRKEPEP 370 380 390 400 410 KGPAKKKAKT GGAGKFRRGK INLSFPSTVL DPRLSICFVP SAAAHPSCPS S

References

[1]	"High-efficiency full-length cDNA cloning." Carninci P., Hayashizaki Y. Methods Enzymol. 303:19-44(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
[2]	"Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes." Carninci P., Shibata Y., Hayatsu N., Sugahara Y., Shibata K., Itoh M., Konno H., Okazaki Y., Muramatsu M., Hayashizaki Y. Genome Res. 10:1617-1630(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
[3]	"RIKEN integrated sequence analysis (RISA) system--384-format sequencing pipeline with 384 multicapillary sequencer." Shibata K., Itoh M., Aizawa K., Nagaoka S., Sasaki N., Carninci P., Konno H., Akiyama J., Nishi K., Kitsunai T., Tashiro H., Itoh M., Sumi N., Ishii Y., Nakamura S., Hazama M., Nishine T., Harada A. , Yamamoto R., Matsumoto H., Sakaguchi S., Ikegami T., Kashiwagi K., Fujiwake S., Inoue K., Togawa Y., Izawa M., Ohara E., Watahiki M., Yoneda Y., Ishikawa T., Ozawa K., Tanaka T., Matsuura S., Kawai J., Okazaki Y., Muramatsu M., Inoue Y., Kira A., Hayashizaki Y. Genome Res. 10:1757-1771(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
[4]	"Functional annotation of a full-length mouse cDNA collection." The RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium Nature 409:685-690(2001) Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
[5]	"Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs." The FANTOM Consortium and the RIKEN Genome Exploration Research Group Phase I and II Team Nature 420:563-573(2002) Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
[6]	Adachi J., Aizawa K., Akimura T., Arakawa T., Bono H., Carninci P., Fukuda S., Furuno M., Hanagaki T., Hara A., Hashizume W., Hayashida K., Hayatsu N., Hiramoto K., Hiraoka T., Hirozane T., Hori F., Imotani K. , Ishii Y., Itoh M., Kagawa I., Kasukawa T., Katoh H., Kawai J., Kojima Y., Kondo S., Konno H., Kouda M., Koya S., Kurihara C., Matsuyama T., Miyazaki A., Murata M., Nakamura M., Nishi K., Nomura K., Numazaki R., Ohno M., Ohsato N., Okazaki Y., Saito R., Saitoh H., Sakai C., Sakai K., Sakazume N., Sano H., Sasaki D., Shibata K., Shinagawa A., Shiraki T., Sogabe Y., Tagami M., Tagawa A., Takahashi F., Takaku-Akahira S., Takeda Y., Tanaka T., Tomaru A., Toya T., Yasunishi A., Muramatsu M., Hayashizaki Y. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
[7]	"The Transcriptional Landscape of the Mammalian Genome." The FANTOM Consortium, Riken Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group) Science 309:1559-1563(2005) Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
[8]	"Antisense Transcription in the Mammalian Transcriptome." RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group) and the FANTOM Consortium Science 309:1564-1566(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J EMBL BAC36544.1. Tissue: Testis EMBL BAC36544.1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK076977 mRNA. Translation: BAC36544.1.
IPI	IPI00410836.
UniGene	Mm.2952.
3D structure databases
HSSP	HSSP built from PDB template 1B43 based on UniProtKB O93634.
ProteinModelPortal	Q8C5X6.
SMR	Q8C5X6. Positions 2-356.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8C5X6.
PTM databases
PhosphoSite	Q8C5X6.
Proteomic databases
PRIDE	Q8C5X6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:102779. Fen1.
Phylogenomic databases
HOGENOM	HOG000193853.
HOVERGEN	HBG000844.
InParanoid	Q8C5X6.
Gene expression databases
ArrayExpress	Q8C5X6.
Bgee	Q8C5X6.
Genevestigator	Q8C5X6.
Family and domain databases
HAMAP	MF_00614. Fen.
InterPro	IPR020045. 5-3_exonuclease_C. IPR023426. Flap_endonuc. IPR008918. HhH2. IPR006086. XPG-I_dom. IPR006084. XPG/Rad2. IPR019974. XPG_CS. IPR006085. XPG_DNA_repair_N. [Graphical view]
PANTHER	PTHR11081. PTHR11081. 1 hit.
Pfam	PF00867. XPG_I. 1 hit. PF00752. XPG_N. 1 hit. [Graphical view]
PRINTS	PR00853. XPGRADSUPER.
SMART	SM00279. HhH2. 1 hit. SM00484. XPGI. 1 hit. SM00485. XPGN. 1 hit. [Graphical view]
SUPFAM	SSF47807. 5_3_exo_C. 1 hit.
PROSITE	PS00841. XPG_1. 1 hit. PS00842. XPG_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FEN1. mouse.
SOURCE	Search...

Entry information

Entry name

Q8C5X6_MOUSE

Accession

Primary (citable) accession number: Q8C5X6

Entry history

Integrated into UniProtKB/TrEMBL:	March 1, 2003
Last sequence update:	March 1, 2003
Last modified:	April 3, 2013
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)