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Protein

Proliferating cell nuclear antigen

Gene

Pcna

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
DNA bindingi61 – 80Sequence analysisAdd BLAST20

GO - Molecular functioni

GO - Biological processi

  • base-excision repair, gap-filling Source: MGI
  • cellular response to UV Source: UniProtKB
  • cellular response to xenobiotic stimulus Source: MGI
  • leading strand elongation Source: GO_Central
  • mismatch repair Source: MGI
  • mitotic telomere maintenance via semi-conservative replication Source: BHF-UCL
  • negative regulation of transcription by RNA polymerase II Source: MGI
  • positive regulation of deoxyribonuclease activity Source: UniProtKB
  • positive regulation of DNA repair Source: UniProtKB
  • positive regulation of DNA replication Source: UniProtKB
  • replication fork processing Source: BHF-UCL
  • response to lipid Source: MGI
  • translesion synthesis Source: UniProtKB

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair, DNA replication

Enzyme and pathway databases

ReactomeiR-MMU-110312 Translesion synthesis by REV1
R-MMU-110314 Recognition of DNA damage by PCNA-containing replication complex
R-MMU-110320 Translesion Synthesis by POLH
R-MMU-174411 Polymerase switching on the C-strand of the telomere
R-MMU-174414 Processive synthesis on the C-strand of the telomere
R-MMU-174417 Telomere C-strand (Lagging Strand) Synthesis
R-MMU-174437 Removal of the Flap Intermediate from the C-strand
R-MMU-4615885 SUMOylation of DNA replication proteins
R-MMU-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-MMU-5651801 PCNA-Dependent Long Patch Base Excision Repair
R-MMU-5655862 Translesion synthesis by POLK
R-MMU-5656121 Translesion synthesis by POLI
R-MMU-5656169 Termination of translesion DNA synthesis
R-MMU-5685942 HDR through Homologous Recombination (HRR)
R-MMU-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER
R-MMU-5696400 Dual Incision in GG-NER
R-MMU-6782135 Dual incision in TC-NER
R-MMU-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-MMU-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-MMU-69091 Polymerase switching
R-MMU-69166 Removal of the Flap Intermediate
R-MMU-69183 Processive synthesis on the lagging strand

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:97503 Pcna

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001491601 – 261Proliferating cell nuclear antigenAdd BLAST261

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14N6-acetyllysineBy similarity1
Modified residuei77N6-acetyllysineBy similarity1
Modified residuei80N6-acetyllysineBy similarity1
Cross-linki164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei211Phosphotyrosine; by EGFR1 Publication1
Modified residuei248N6-acetyllysineBy similarity1
Cross-linki254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By 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

EPDiP17918
PaxDbiP17918
PeptideAtlasiP17918
PRIDEiP17918
TopDownProteomicsiP17918

2D gel databases

REPRODUCTION-2DPAGEiP17918

PTM databases

iPTMnetiP17918
PhosphoSitePlusiP17918
SwissPalmiP17918

Expressioni

Inductioni

Induced in IL2-stimulated proliferating T-lymphocytes.

Gene expression databases

BgeeiENSMUSG00000027342
CleanExiMM_PCNA
ExpressionAtlasiP17918 baseline and differential
GenevisibleiP17918 MM

Interactioni

Subunit structurei

Homotrimer. 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. Directly interacts with POLD1, POLD3 and POLD4 subunits of the DNA polymerase delta complex, POLD3 being the major interacting partner; the interaction with POLD3 is inhibited by CDKN1A/p21(CIP1). Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with EXO1, POLH, POLK, DNMT1, ERCC5, FEN1, CDC6 and POLDIP2 (By similarity). Interacts with APEX2; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA (PubMed:12573260). Forms a ternary complex with DNTTIP2 and core histone (By similarity). Interacts with KCTD10 (By similarity). Interacts with PPP1R15A (PubMed:9371605). Directly interacts with BAZ1B. Interacts with HLTF and SHPRH. Interacts with NUDT15; this 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. The interaction with CDKN1A inhibits POLD3 binding. 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 PCLAF (via PIP-box) (By similarity). Interacts with RTEL1 (via PIP-box); the interaction is direct and essential for the suppression of telomere fragility (PubMed:24115439). Interacts with FAM111A (via PIP-box); the interaction is direct and required for PCNA loading on chromatin binding. Interacts with LIG1. Interacts with SETMAR. Interacts with ANKRD17. Interacts with FBXO18/FBH1 (via PIP-box); the interaction recruits the DCX(DTL) complex and promotes ubiquitination and degradation of FBXO18/FBH1. Interacts with POLN (By similarity). Interacts with SDE2 (via PIP-box); the interaction is direct and prevents ultraviolet light induced monoubiquitination (By similarity). Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR; interaction at least with PCNA occurs during DNA replication (By similarity). Interacts with MAPK15; the interaction is chromatin binding dependent and prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2 (By similarity).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202049, 50 interactors
ComplexPortaliCPX-541 PCNA homotrimer
CORUMiP17918
DIPiDIP-39409N
IntActiP17918, 40 interactors
MINTiP17918
STRINGi10090.ENSMUSP00000028817

Structurei

3D structure databases

ProteinModelPortaliP17918
SMRiP17918
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the PCNA family.Curated

Phylogenomic databases

eggNOGiKOG1636 Eukaryota
COG0592 LUCA
GeneTreeiENSGT00390000004965
HOVERGENiHBG000947
InParanoidiP17918
KOiK04802
OMAiSDGFDKY
OrthoDBiEOG091G0GQ7
PhylomeDBiP17918
TreeFamiTF313441

Family and domain databases

HAMAPiMF_00317 DNApol_clamp_arch, 1 hit
InterProiView protein in InterPro
IPR000730 Pr_cel_nuc_antig
IPR022649 Pr_cel_nuc_antig_C
IPR022659 Pr_cel_nuc_antig_CS
IPR022648 Pr_cel_nuc_antig_N
PANTHERiPTHR11352:SF0 PTHR11352:SF0, 1 hit
PfamiView protein in Pfam
PF02747 PCNA_C, 1 hit
PF00705 PCNA_N, 1 hit
PRINTSiPR00339 PCNACYCLIN
TIGRFAMsiTIGR00590 pcna, 1 hit
PROSITEiView protein in PROSITE
PS01251 PCNA_1, 1 hit
PS00293 PCNA_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti3 – 5EAR → LES no nucleotide entry (PubMed:2906640).Curated3
Sequence conflicti67A → T in CAA37243 (PubMed:1674997).Curated1

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.391640
Mm.7141

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiPCNA_MOUSE
AccessioniPrimary (citable) accession number: P17918
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 1, 1992
Last modified: June 20, 2018
This is version 184 of the entry and version 2 of the sequence. See 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

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