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P17918 (PCNA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proliferating cell nuclear antigen

Short name=PCNA
Alternative name(s):
Cyclin
Gene names
Name:Pcna
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length261 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion By similarity. HAMAP-Rule MF_00317

Subunit structure

Homotrimer By similarity. Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with EXO1, POLH, POLK, DNMT1, ERCC5, FEN1, CDC6 and POLDIP2. Interacts with APEX2; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA. Forms a ternary complex with DNTTIP2 and core histone. Interacts with KCTD10 and PPP1R15A. Interacts with POLD1, POLD3 and POLD4. Interacts with BAZ1B; the interaction is direct. Interacts with HLTF and SHPRH. Interacts with NUDT15. Interaction is disrupted in response to UV irradiation and acetylation. Interacts with CDKN1A/p21(CIP1) and CDT1; interacts via their PIP-box which also recruits the DCX(DTL) complex. Interacts with DDX11. Interacts with EGFR; positively regulates PCNA. Interacts with PARPBP. Interacts (when ubiquitinated) with SPRTN; leading to enhance RAD18-mediated PCNA ubiquitination. Interacts (when polyubiquitinated) with ZRANB3. Interacts with SMARCAD1. Interacts with CDKN1C. Interacts with KIAA0101/PAF15 (via PIP-box). Interacts with RTEL1 (via PIP-box); the interaction is direct and essential for the suppression of telomere fragility. Interacts with FAM111A (via PIP-box); the interaction is direct and required for PCNA loading on chromatin binding. Ref.5 Ref.6 Ref.9

Subcellular location

Nucleus. Note: Forms nuclear foci representing sites of ongoing DNA replication and vary in morphology and number during S phase. Together with APEX2, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents. Ref.9

Induction

Induced in IL2-stimulated proliferating T-lymphocytes. HAMAP-Rule MF_00317

Post-translational modification

Following DNA damage, can be either monoubiquitinated to stimulate direct bypass of DNA lesions by specialized DNA polymerases or polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Following induction of replication stress, monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to recruit translesion (TLS) polymerases, which are able to synthesize across DNA lesions in a potentially error-prone manner. An error-free pathway also exists and requires non-canonical polyubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH. This error-free pathway, also known as template switching, employs recombination mechanisms to synthesize across the lesion, using as a template the undamaged, newly synthesized strand of the sister chromatid. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis. Sumoylated during S phase By similarity. HAMAP-Rule MF_00317

Acetylated in response to UV irradiation. Acetylation disrupts interaction with NUDT15 and promotes degradation By similarity. HAMAP-Rule MF_00317

Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA By similarity. Ref.7

Sequence similarities

Belongs to the PCNA family.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
DNA replication
   Cellular componentNucleus
   LigandDNA-binding
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from electronic annotation. Source: UniProtKB-KW

base-excision repair, gap-filling

Inferred from direct assay PubMed 15177179. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19023449. Source: MGI

positive regulation of deoxyribonuclease activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of DNA replication

Inferred from electronic annotation. Source: InterPro

translesion synthesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentPCNA complex

Inferred from electronic annotation. Source: InterPro

PCNA-p21 complex

Inferred from sequence or structural similarity. Source: UniProtKB

centrosome

Inferred from sequence orthology PubMed 18331714. Source: MGI

cyclin-dependent protein kinase holoenzyme complex

Inferred from physical interaction PubMed 12970760. Source: MGI

intracellular

Inferred from direct assay PubMed 16489008. Source: MGI

nuclear lamina

Inferred from direct assay PubMed 10888872. Source: MGI

nucleus

Inferred from direct assay PubMed 10079221PubMed 11942627PubMed 11981756PubMed 12040017PubMed 12203718PubMed 12638230PubMed 12970760PubMed 14703996PubMed 18692037PubMed 19023449PubMed 23284756PubMed 23976951. Source: MGI

replication fork

Inferred from direct assay PubMed 11934988. Source: MGI

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA polymerase processivity factor activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 11022036PubMed 17274640. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Gadd45gQ9Z1112EBI-1173716,EBI-1173616
Ppp1caP621372EBI-1173716,EBI-357187

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 261261Proliferating cell nuclear antigen HAMAP-Rule MF_00317
PRO_0000149160

Regions

DNA binding61 – 8020 Potential

Amino acid modifications

Modified residue141N6-acetyllysine By similarity
Modified residue771N6-acetyllysine By similarity
Modified residue801N6-acetyllysine Ref.8
Modified residue2111Phosphotyrosine; by EGFR Ref.7
Modified residue2481N6-acetyllysine By similarity
Cross-link164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict3 – 53EAR → LES no nucleotide entry Ref.4
Sequence conflict671A → T in CAA37243. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P17918 [UniParc].

Last modified March 1, 1992. Version 2.
Checksum: F705CCBDD3205986

FASTA26128,785
        10         20         30         40         50         60 
MFEARLIQGS ILKKVLEALK DLINEACWDV SSGGVNLQSM DSSHVSLVQL TLRSEGFDTY 

        70         80         90        100        110        120 
RCDRNLAMGV NLTSMSKILK CAGNEDIITL RAEDNADTLA LVFEAPNQEK VSDYEMKLMD 

       130        140        150        160        170        180 
LDVEQLGIPE QEYSCVIKMP SGEFARICRD LSHIGDAVVI SCAKNGVKFS ASGELGNGNI 

       190        200        210        220        230        240 
KLSQTSNVDK EEEAVTIEMN EPVHLTFALR YLNFFTKATP LSPTVTLSMS ADVPLVVEYK 

       250        260 
IADMGHLKYY LAPKIEDEEA S 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of murine PCNA: interspecies comparison of the cDNA and the 5' flanking region of the gene."
Shipman-Appasamy P.M., Cohen K.S., Prystowsky M.B.
DNA Seq. 2:181-191(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
Tissue: Lymphoid tissue.
[2]"Molecular cloning and structural analysis of mouse gene and pseudogenes for proliferating cell nuclear antigen."
Yamaguchi M., Hayashi Y., Hirose F., Matsuoka S., Moriuchi T., Shiroishi T., Moriwaki K., Matsukage A.
Nucleic Acids Res. 19:2403-2410(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: C57BL/6.
Tissue: Spleen.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary gland.
[4]"Cyclin mRNA and protein expression in recombinant interleukin 2-stimulated cloned murine T lymphocytes."
Shipman P.M., Sabath D.E., Fischer A.H., Comber P.G., Sullivan K., Tan E.M., Prystowsky M.B.
J. Cell. Biochem. 38:189-198(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-42.
Tissue: T-cell.
[5]"The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34."
Brown S.M., MacLean A.R., McKie E.A., Harland J.
J. Virol. 71:9442-9449(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPP1R15A AND HHV-1 ICP34.5.
[6]"Characterization of the genomic structure and expression of the mouse Apex2 gene."
Ide Y., Tsuchimoto D., Tominaga Y., Iwamoto Y., Nakabeppu Y.
Genomics 81:47-57(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APEX2.
[7]"Tyrosine phosphorylation controls PCNA function through protein stability."
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-211.
[8]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-80, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[9]"RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication."
Vannier J.B., Sandhu S., Petalcorin M.I., Wu X., Nabi Z., Ding H., Boulton S.J.
Science 342:239-242(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RTEL1, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X53068 mRNA. Translation: CAA37243.1.
X57800 Genomic DNA. Translation: CAA40938.1.
BC005778 mRNA. Translation: AAH05778.1.
BC010343 mRNA. Translation: AAH10343.1.
CCDSCCDS16771.1.
PIRWMMS. S15703.
RefSeqNP_035175.1. NM_011045.2.
UniGeneMm.7141.

3D structure databases

ProteinModelPortalP17918.
SMRP17918. Positions 1-257.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202049. 20 interactions.
DIPDIP-39409N.
IntActP17918. 9 interactions.
MINTMINT-1510748.

PTM databases

PhosphoSiteP17918.

2D gel databases

REPRODUCTION-2DPAGEP17918.

Proteomic databases

MaxQBP17918.
PaxDbP17918.
PRIDEP17918.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028817; ENSMUSP00000028817; ENSMUSG00000027342.
GeneID18538.
KEGGmmu:18538.
UCSCuc008mml.1. mouse.

Organism-specific databases

CTD5111.
MGIMGI:97503. Pcna.

Phylogenomic databases

eggNOGCOG0592.
HOVERGENHBG000947.
InParanoidP17918.
KOK04802.
OMAMKLMNLD.
OrthoDBEOG7JX34W.
PhylomeDBP17918.
TreeFamTF313441.

Gene expression databases

BgeeP17918.
CleanExMM_PCNA.
GenevestigatorP17918.

Family and domain databases

HAMAPMF_00317. DNApol_clamp_arch.
InterProIPR000730. Pr_cel_nuc_antig.
IPR022649. Pr_cel_nuc_antig_C.
IPR022659. Pr_cel_nuc_antig_CS.
IPR022648. Pr_cel_nuc_antig_N.
[Graphical view]
PANTHERPTHR11352. PTHR11352. 1 hit.
PfamPF02747. PCNA_C. 1 hit.
PF00705. PCNA_N. 1 hit.
[Graphical view]
PRINTSPR00339. PCNACYCLIN.
TIGRFAMsTIGR00590. pcna. 1 hit.
PROSITEPS01251. PCNA_1. 1 hit.
PS00293. PCNA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294312.
PROP17918.
SOURCESearch...

Entry information

Entry namePCNA_MOUSE
AccessionPrimary (citable) accession number: P17918
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 1, 1992
Last modified: July 9, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot