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P17918

- PCNA_MOUSE

UniProt

P17918 - PCNA_MOUSE

Protein

Proliferating cell nuclear antigen

Gene

Pcna

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 2 (01 Mar 1992)
      Previous versions | rss
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    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

    1. DNA binding Source: UniProtKB-KW
    2. DNA polymerase processivity factor activity Source: InterPro
    3. protein binding Source: IntAct

    GO - Biological processi

    1. base-excision repair, gap-filling Source: MGI
    2. leading strand elongation Source: RefGenome
    3. mismatch repair Source: RefGenome
    4. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    5. positive regulation of deoxyribonuclease activity Source: UniProtKB
    6. regulation of DNA replication Source: InterPro
    7. translesion synthesis Source: UniProtKB

    Keywords - Biological processi

    DNA damage, DNA repair, DNA replication

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_198608. G1/S-Specific Transcription.
    REACT_199110. G0 and Early G1.
    REACT_206830. E2F mediated regulation of DNA replication.
    REACT_209299. Repair synthesis of patch ~27-30 bases long by DNA polymerase.
    REACT_216529. Removal of the Flap Intermediate from the C-strand.
    REACT_219337. Removal of DNA patch containing abasic residue.
    REACT_219381. Repair synthesis for gap-filling by DNA polymerase in TC-NER.
    REACT_220175. Telomere C-strand (Lagging Strand) Synthesis.
    REACT_223154. Processive synthesis on the C-strand of the telomere.
    REACT_225604. Polymerase switching on the C-strand of the telomere.

    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: Chromosome 2

    Organism-specific databases

    MGIiMGI:97503. Pcna.

    Subcellular locationi

    Nucleus 1 Publication
    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.

    GO - Cellular componenti

    1. centrosome Source: MGI
    2. cyclin-dependent protein kinase holoenzyme complex Source: MGI
    3. intracellular Source: MGI
    4. nuclear lamina Source: MGI
    5. nucleus Source: MGI
    6. PCNA complex Source: RefGenome
    7. PCNA-p21 complex Source: UniProtKB
    8. replication fork Source: MGI

    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

    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
    Acetylated in response to UV irradiation. Acetylation disrupts interaction with NUDT15 and promotes degradation By similarity.By similarity
    Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA By similarity.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, 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.
    GenevestigatoriP17918.

    Interactioni

    Subunit structurei

    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.By similarity3 Publications

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi202049. 20 interactions.
    DIPiDIP-39409N.
    IntActiP17918. 10 interactions.
    MINTiMINT-1510748.

    Structurei

    3D structure databases

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

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the PCNA family.Curated

    Phylogenomic databases

    eggNOGiCOG0592.
    HOVERGENiHBG000947.
    InParanoidiP17918.
    KOiK04802.
    OMAiMKLMNLD.
    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

    MFEARLIQGS ILKKVLEALK DLINEACWDV SSGGVNLQSM DSSHVSLVQL    50
    TLRSEGFDTY RCDRNLAMGV NLTSMSKILK CAGNEDIITL RAEDNADTLA 100
    LVFEAPNQEK VSDYEMKLMD LDVEQLGIPE QEYSCVIKMP SGEFARICRD 150
    LSHIGDAVVI SCAKNGVKFS ASGELGNGNI KLSQTSNVDK EEEAVTIEMN 200
    EPVHLTFALR YLNFFTKATP LSPTVTLSMS ADVPLVVEYK IADMGHLKYY 250
    LAPKIEDEEA S 261
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X53068 mRNA. Translation: CAA37243.1 .
    X57800 Genomic DNA. Translation: CAA40938.1 .
    BC005778 mRNA. Translation: AAH05778.1 .
    BC010343 mRNA. Translation: AAH10343.1 .
    CCDSi CCDS16771.1.
    PIRi S15703. WMMS.
    RefSeqi NP_035175.1. NM_011045.2.
    UniGenei Mm.7141.

    3D structure databases

    ProteinModelPortali P17918.
    SMRi P17918. Positions 1-257.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202049. 20 interactions.
    DIPi DIP-39409N.
    IntActi P17918. 10 interactions.
    MINTi MINT-1510748.

    PTM databases

    PhosphoSitei P17918.

    2D gel databases

    REPRODUCTION-2DPAGE P17918.

    Proteomic databases

    MaxQBi P17918.
    PaxDbi P17918.
    PRIDEi P17918.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000028817 ; ENSMUSP00000028817 ; ENSMUSG00000027342 .
    GeneIDi 18538.
    KEGGi mmu:18538.
    UCSCi uc008mml.1. mouse.

    Organism-specific databases

    CTDi 5111.
    MGIi MGI:97503. Pcna.

    Phylogenomic databases

    eggNOGi COG0592.
    HOVERGENi HBG000947.
    InParanoidi P17918.
    KOi K04802.
    OMAi MKLMNLD.
    OrthoDBi EOG7JX34W.
    PhylomeDBi P17918.
    TreeFami TF313441.

    Enzyme and pathway databases

    Reactomei REACT_198608. G1/S-Specific Transcription.
    REACT_199110. G0 and Early G1.
    REACT_206830. E2F mediated regulation of DNA replication.
    REACT_209299. Repair synthesis of patch ~27-30 bases long by DNA polymerase.
    REACT_216529. Removal of the Flap Intermediate from the C-strand.
    REACT_219337. Removal of DNA patch containing abasic residue.
    REACT_219381. Repair synthesis for gap-filling by DNA polymerase in TC-NER.
    REACT_220175. Telomere C-strand (Lagging Strand) Synthesis.
    REACT_223154. Processive synthesis on the C-strand of the telomere.
    REACT_225604. Polymerase switching on the C-strand of the telomere.

    Miscellaneous databases

    NextBioi 294312.
    PROi P17918.
    SOURCEi Search...

    Gene expression databases

    Bgeei P17918.
    CleanExi MM_PCNA.
    Genevestigatori P17918.

    Family and domain databases

    HAMAPi MF_00317. DNApol_clamp_arch.
    InterProi IPR000730. Pr_cel_nuc_antig.
    IPR022649. Pr_cel_nuc_antig_C.
    IPR022659. Pr_cel_nuc_antig_CS.
    IPR022648. Pr_cel_nuc_antig_N.
    [Graphical view ]
    PANTHERi PTHR11352. PTHR11352. 1 hit.
    Pfami PF02747. PCNA_C. 1 hit.
    PF00705. PCNA_N. 1 hit.
    [Graphical view ]
    PRINTSi PR00339. PCNACYCLIN.
    TIGRFAMsi TIGR00590. pcna. 1 hit.
    PROSITEi PS01251. PCNA_1. 1 hit.
    PS00293. PCNA_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 144 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