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Protein

Proliferating cell nuclear antigen

Gene

Pcna

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi61 – 8020Sequence AnalysisAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair, DNA replication

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_274086. G0 and Early G1.
REACT_276436. Processive synthesis on the lagging strand.
REACT_278371. Processive synthesis on the C-strand of the telomere.
REACT_278538. Repair synthesis for gap-filling by DNA polymerase in TC-NER.
REACT_283766. Polymerase switching.
REACT_290560. Leading Strand Synthesis.
REACT_303128. Translesion synthesis by REV1.
REACT_303193. Removal of the Flap Intermediate.
REACT_304724. Telomere C-strand (Lagging Strand) Synthesis.
REACT_314754. E2F mediated regulation of DNA replication.
REACT_320650. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
REACT_329955. Removal of the Flap Intermediate from the C-strand.
REACT_330619. Polymerase switching on the C-strand of the telomere.
REACT_331202. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
REACT_332983. Translesion Synthesis by POLH.
REACT_339329. G1/S-Specific Transcription.
REACT_342741. Repair synthesis of patch ~27-30 bases long by DNA polymerase.
REACT_358684. Recognition of DNA damage by PCNA-containing replication complex.
REACT_361112. Translesion synthesis by POLI.
REACT_361486. PCNA-Dependent Long Patch Base Excision Repair.
REACT_361949. Translesion synthesis by POLK.
REACT_362050. Termination of translesion DNA synthesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Proliferating cell nuclear antigen
Short name:
PCNA
Alternative name(s):
Cyclin
Gene namesi
Name:Pcna
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:97503. Pcna.

Subcellular locationi

  • Nucleus 1 Publication

  • Note: Colocalizes with CREBBP, EP300 and POLD1 to sites of DNA damage (By similarity). 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.By similarity

GO - Cellular componenti

  • centrosome Source: MGI
  • cyclin-dependent protein kinase holoenzyme complex Source: MGI
  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • intracellular Source: MGI
  • nuclear lamina Source: MGI
  • nuclear replication fork Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • PCNA complex Source: UniProtKB
  • PCNA-p21 complex Source: UniProtKB
  • replication fork Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 261261Proliferating cell nuclear antigenPRO_0000149160Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141N6-acetyllysineBy similarity
Modified residuei77 – 771N6-acetyllysineBy similarity
Modified residuei80 – 801N6-acetyllysine1 Publication
Cross-linki164 – 164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei211 – 2111Phosphotyrosine; by EGFR1 Publication
Modified residuei248 – 2481N6-acetyllysineBy similarity

Post-translational modificationi

Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA (By similarity).By similarity
Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation. Lysine acetylation disrupts association with chromatin, hence promoting PCNA ubiquitination and proteasomal degradation in response to UV damage in a CREBBP- and EP300-dependent manner. Acetylation disrupts interaction with NUDT15 and promotes degradation (By similarity).By similarity
Ubiquitinated. 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).By similarity
Methylated on glutamate residues by ARMT1.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP17918.
PaxDbiP17918.
PRIDEiP17918.

2D gel databases

REPRODUCTION-2DPAGEP17918.

PTM databases

PhosphoSiteiP17918.

Expressioni

Inductioni

Induced in IL2-stimulated proliferating T-lymphocytes.

Gene expression databases

BgeeiP17918.
CleanExiMM_PCNA.
ExpressionAtlasiP17918. baseline and differential.
GenevisibleiP17918. MM.

Interactioni

Subunit structurei

Homotrimer (By similarity). Interacts with p300/EP300; the interaction occurs on chromatin in UV-irradiated damaged cells. Interacts with CREBBP (via transactivation domain and C-terminus); the interaction occurs on chromatin in UV-irradiated damaged cells (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. Interacts with LIG1. Interacts with SETMAR.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Gadd45gQ9Z1112EBI-1173716,EBI-1173616
Ppp1caP621372EBI-1173716,EBI-357187

Protein-protein interaction databases

BioGridi202049. 22 interactions.
DIPiDIP-39409N.
IntActiP17918. 10 interactions.
MINTiMINT-1510748.
STRINGi10090.ENSMUSP00000028817.

Structurei

3D structure databases

ProteinModelPortaliP17918.
SMRiP17918. Positions 1-257.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the PCNA family.Curated

Phylogenomic databases

eggNOGiCOG0592.
GeneTreeiENSGT00390000004965.
HOVERGENiHBG000947.
InParanoidiP17918.
KOiK04802.
OMAiKMMDIDS.
OrthoDBiEOG7JX34W.
PhylomeDBiP17918.
TreeFamiTF313441.

Family and domain databases

HAMAPiMF_00317. DNApol_clamp_arch.
InterProiIPR000730. Pr_cel_nuc_antig.
IPR022649. Pr_cel_nuc_antig_C.
IPR022659. Pr_cel_nuc_antig_CS.
IPR022648. Pr_cel_nuc_antig_N.
[Graphical view]
PANTHERiPTHR11352. PTHR11352. 1 hit.
PfamiPF02747. PCNA_C. 1 hit.
PF00705. PCNA_N. 1 hit.
[Graphical view]
PRINTSiPR00339. PCNACYCLIN.
TIGRFAMsiTIGR00590. pcna. 1 hit.
PROSITEiPS01251. PCNA_1. 1 hit.
PS00293. PCNA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P17918-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFEARLIQGS ILKKVLEALK DLINEACWDV SSGGVNLQSM DSSHVSLVQL
60 70 80 90 100
TLRSEGFDTY RCDRNLAMGV NLTSMSKILK CAGNEDIITL RAEDNADTLA
110 120 130 140 150
LVFEAPNQEK VSDYEMKLMD LDVEQLGIPE QEYSCVIKMP SGEFARICRD
160 170 180 190 200
LSHIGDAVVI SCAKNGVKFS ASGELGNGNI KLSQTSNVDK EEEAVTIEMN
210 220 230 240 250
EPVHLTFALR YLNFFTKATP LSPTVTLSMS ADVPLVVEYK IADMGHLKYY
260
LAPKIEDEEA S
Length:261
Mass (Da):28,785
Last modified:March 1, 1992 - v2
Checksum:iF705CCBDD3205986
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 53EAR → LES no nucleotide entry (PubMed:2906640).Curated
Sequence conflicti67 – 671A → T in CAA37243 (PubMed:1674997).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53068 mRNA. Translation: CAA37243.1.
X57800 Genomic DNA. Translation: CAA40938.1.
BC005778 mRNA. Translation: AAH05778.1.
BC010343 mRNA. Translation: AAH10343.1.
CCDSiCCDS16771.1.
PIRiS15703. WMMS.
RefSeqiNP_035175.1. NM_011045.2.
UniGeneiMm.7141.

Genome annotation databases

EnsembliENSMUST00000028817; ENSMUSP00000028817; ENSMUSG00000027342.
GeneIDi18538.
KEGGimmu:18538.
UCSCiuc008mml.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53068 mRNA. Translation: CAA37243.1.
X57800 Genomic DNA. Translation: CAA40938.1.
BC005778 mRNA. Translation: AAH05778.1.
BC010343 mRNA. Translation: AAH10343.1.
CCDSiCCDS16771.1.
PIRiS15703. WMMS.
RefSeqiNP_035175.1. NM_011045.2.
UniGeneiMm.7141.

3D structure databases

ProteinModelPortaliP17918.
SMRiP17918. Positions 1-257.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202049. 22 interactions.
DIPiDIP-39409N.
IntActiP17918. 10 interactions.
MINTiMINT-1510748.
STRINGi10090.ENSMUSP00000028817.

PTM databases

PhosphoSiteiP17918.

2D gel databases

REPRODUCTION-2DPAGEP17918.

Proteomic databases

MaxQBiP17918.
PaxDbiP17918.
PRIDEiP17918.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028817; ENSMUSP00000028817; ENSMUSG00000027342.
GeneIDi18538.
KEGGimmu:18538.
UCSCiuc008mml.1. mouse.

Organism-specific databases

CTDi5111.
MGIiMGI:97503. Pcna.

Phylogenomic databases

eggNOGiCOG0592.
GeneTreeiENSGT00390000004965.
HOVERGENiHBG000947.
InParanoidiP17918.
KOiK04802.
OMAiKMMDIDS.
OrthoDBiEOG7JX34W.
PhylomeDBiP17918.
TreeFamiTF313441.

Enzyme and pathway databases

ReactomeiREACT_274086. G0 and Early G1.
REACT_276436. Processive synthesis on the lagging strand.
REACT_278371. Processive synthesis on the C-strand of the telomere.
REACT_278538. Repair synthesis for gap-filling by DNA polymerase in TC-NER.
REACT_283766. Polymerase switching.
REACT_290560. Leading Strand Synthesis.
REACT_303128. Translesion synthesis by REV1.
REACT_303193. Removal of the Flap Intermediate.
REACT_304724. Telomere C-strand (Lagging Strand) Synthesis.
REACT_314754. E2F mediated regulation of DNA replication.
REACT_320650. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
REACT_329955. Removal of the Flap Intermediate from the C-strand.
REACT_330619. Polymerase switching on the C-strand of the telomere.
REACT_331202. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
REACT_332983. Translesion Synthesis by POLH.
REACT_339329. G1/S-Specific Transcription.
REACT_342741. Repair synthesis of patch ~27-30 bases long by DNA polymerase.
REACT_358684. Recognition of DNA damage by PCNA-containing replication complex.
REACT_361112. Translesion synthesis by POLI.
REACT_361486. PCNA-Dependent Long Patch Base Excision Repair.
REACT_361949. Translesion synthesis by POLK.
REACT_362050. Termination of translesion DNA synthesis.

Miscellaneous databases

NextBioi294312.
PROiP17918.
SOURCEiSearch...

Gene expression databases

BgeeiP17918.
CleanExiMM_PCNA.
ExpressionAtlasiP17918. baseline and differential.
GenevisibleiP17918. MM.

Family and domain databases

HAMAPiMF_00317. DNApol_clamp_arch.
InterProiIPR000730. Pr_cel_nuc_antig.
IPR022649. Pr_cel_nuc_antig_C.
IPR022659. Pr_cel_nuc_antig_CS.
IPR022648. Pr_cel_nuc_antig_N.
[Graphical view]
PANTHERiPTHR11352. PTHR11352. 1 hit.
PfamiPF02747. PCNA_C. 1 hit.
PF00705. PCNA_N. 1 hit.
[Graphical view]
PRINTSiPR00339. PCNACYCLIN.
TIGRFAMsiTIGR00590. pcna. 1 hit.
PROSITEiPS01251. PCNA_1. 1 hit.
PS00293. PCNA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiPCNA_MOUSE
AccessioniPrimary (citable) accession number: P17918
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 1, 1992
Last modified: July 22, 2015
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.