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Symbol PCNA contributors: mct/npt/pgu - updated : 23-03-2017
HGNC name proliferating cell nuclear antigen
HGNC id 8729
Location 20p12.3      Physical location : 5.095.599 - 5.107.268
Synonym name
  • cyclin
  • DNA polymerase delta auxiliary protein
  • Synonym symbol(s) MGC8367
    TYPE functioning gene
    STRUCTURE 5.05 kb     6 Exon(s)    one Copie(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure
  • a Y-box sequence 5' - CTGATTGG - 3' in its cis-regulatory elements
  • TAAC element is present in the cellular senescence-inhibited gene, PCNA, and CCNA2 promoters
  • MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    text variants 1 and 2 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1355 28.6 261 - 1990 1979311
    6 - 1319 28.6 261 - 1990 1979311
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart   highly
    Digestiveliver   highly
    Endocrineadrenal gland    
    Urinarykidney   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    at STAGE
    conjugated sumoylated
    mono polymer homomer , trimer
    interspecies homolog to murine Pcna
    homolog to C.elegans pcn-1
  • PCNA family
  • CATEGORY regulatory , DNA associated , antigen
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    basic FUNCTION
  • involved in the control of DNA replication by increasing the polymerase processsibility during elongation of the loading strand
  • exonuclease activity linked to the RAD6 pathway of post-replicative DNA repair
  • major regulator of chromatin assembly during DNA repair
  • central matchmaker for replication-linked functions, is also crucially involved in the establishment of cohesion in S phase
  • promotes the DNA damage-induced degradation of the replication initiation factor CDT1 via the DTL E3 ubiquitin ligase complex
  • mono-ubiquitination of PCNA mediates the switch from replicative DNA polymerases to polymerases specialised for translesion synthesis (modification necessary for the survival of cells after UV-irradiation)
  • functions as a sliding clamp for the replicative polymerase Poldelta, also interacts with the three TLS (Translesion synthesis) polymerases
  • promotes cancer survival by immune evasion through inhibition of NCR2-mediated NK cell attack
  • plays potentially a role in the early stage of DNA damage signaling by ATM
  • multifunctional component of DNA replication and repair machinery
  • aberrant lysine methylation of PCNA may play potentially a role in human carcinogenesis
  • RSLISD1, PCNA, and CCNA2, which promote cell cycle progression, are repressed permanently in senescent cells
  • CELLULAR PROCESS cell cycle, progression
    cell life, proliferation/growth
    nucleotide, replication
    nucleotide, repair, base excision repair
    nucleotide, repair, nucleotide excision repair
    nucleotide, repair, mismatch repair
    RAD18-PCNA-DLCRE1A activation pathway appears to be independent of another DNA crosslink repair pathway, the FA (Fanconi anemia) pathway
    a component
  • complexing with RFCs to form a processivity factor (sliding clamp), for DNA polymerases delta and epsilon, also complexing with RFC, FEN1, GADD45, MSH2, MLH1, CDKN1A, LIG1
  • part of USP7-HLTF-PCNA molecular network controlling DNA damage response
    DNA binding
    small molecule
  • binding to EP300, FEN1
  • regulating transcriptional coactivator TAF5L activity and promotes transcriptional repression
  • interacting with POLD3 (POLD3 plays a crucial role in the efficient recycling of PCNA during dissociation-association cycles of pol delta)
  • stably interacts with NEIL1 (PCNA stimulates NEIL1 activity in excising the oxidized base 5-hydroxyuracil from single-stranded DNA sequences including fork structures)
  • intimate relationship between RBBP8 and PCNA may be important for the maintenance of genomic stability in higher eukaryotic organism
  • PCNA is protected by this newly identified partner molecule NUDT15, which is related to DNA synthesis and cell cycle progression
  • DTL recognizes an unusual degron, which is assembled specifically on chromatin via the binding of a specialized PIP box to PCNA
  • interacting with ATAD5 (plays an important role in PCNA deubiquitination in cooperation with the USP1-WDR48 complex)
  • during the DNA damage response, SETD8 interaction with PCNA through a specialized "PIP degron" domain targets it for PCNA-coupled DTL-dependent proteolysis
  • PARG interacts with PCNA, through a PCNA binding site and binding to PCNA contributes to PARG recruitment to DNA damage sites
  • BTBD12 could potentially interact with ubiquitylated FANCD2 or PCNA
  • HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability
  • intracellular trafficking of KDM5C is controlled by its association with PCNA
  • DTL function is coupled to replication and repair because it only ubiquitinates substrates that associate with chromatin-bound PCNA
  • NCR2 interaction with PCNA inhibits NK cell function through NCR2/ITIM
  • ATM bind two regions in PCNA (stimulate DNA polymerase activity in a PCNA-dependent manner)
  • HMGN1 is a new PCNA-interacting protein that enhances the binding of PCNA to chromatin but not to purified DNA
  • importance of SUMO modification of PCNA in preventing replication fork collapse to DNA double-strand breaks and providing genome stability
  • SETD8 regulates the function of proliferating cell nuclear antigen (PCNA) protein through lysine methylation
  • disruption of the PCNA-binding motif impaired recruitment of UNG to S-phase replication foci, demonstrating that PCNA is a major factor for recruitment of UNG to unperturbed replication forks
  • protein that specifically recognizes ubiquitylated PCNA and plays an important role in cellular resistance to UV radiation
  • ZRANB3 is recruited by polyubiquitinated PCNA to promote fork restart following replication arrest
  • ZRANB3 can recognize K63-linked polyubiquitinated PCNA and plays an important role in restarting stalled replication forks
  • SPRTN acts at multiple steps in TLS, stabilizes RAD18 and ubiquitinated PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion
  • KCTD13 is able to interact with MYBL2 and PCNA simultaneously
  • RAD18 is targeted to PCNA by DNA polymerase eta (POLH)
  • ROCK1 and ROCK2 could promote vascular smooth muscle cells (VSMC) proliferation through ERK nuclear translocation, regulating the expression of PCNA and cyclin D1 protein
  • ATAD5 is required for the regulation of chromatin-bound PCNA levels
  • important regulatory role of the USP1-WDR48 complex in HR (homologous recombination) repair through its regulation of the FANCD2-ubiquitinated (Ub) and PCNA-Ub cellular pools
  • ING1 interacts with the proliferating cell nuclear antigen (PCNA) in a UV-inducible manner
  • RTEL1-PCNA interaction promotes normal genome replication
  • DDB2 is a PCNA-binding protein, and that this association is required for DDB2 proteolytic degradation
  • SIVA1 interacts with RAD18 and serves as a molecular bridge between RAD18 and PCNA, thus targeting the E3 ligase activity of RAD18 onto PCNA
  • TRAIP (RNF206) is a novel PCNA-interacting factor that has important roles during mammalian replicative stress responses
  • SDE2 is a new genome surveillance factor regulated by PCNA interaction
  • NEO1 is implicated in the maintenance of neural stem cells in the hippocampus by enhancing PCNA expressions
  • CHTF8-RFC1 is an alternative PCNA loader which plays important but poorly understood roles in multiple DNA replication-associated processes
  • N-terminus of USP1 is sufficient to engineer specificity in a more promiscuous USP, but is not required for direct PCNA or FANCI deubiquitination
  • cell & other
    inhibited by ATAD5 (down-regulation of PCNA monoubiquitination by ATAD5 was mediated through an N-terminal 17-AAs sequence of ATAD5, which directly interacts with WDR48)
    Other cell-cycle regulated nuclear protein (UBL1 conjugation to PCNA is regulated by the cell cycle)
    regulated by TSC1 and TSC2
    ubiquitinated by CHEK1 upon DNA damage
    corresponding disease(s)
    Variant & Polymorphism
    Candidate gene
    Therapy target
    inhibition of the PCNA protein-protein interaction can be a new strategy to sensitize cancer cells to chemotherapy