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FLASH GENE
Symbol PCNA contributors: mct/npt/pgu - updated : 23-03-2015
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
    DNA
    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
    MAPPING cloned Y linked N status confirmed
    Physical map
    KIAA1271 20p13 KIAA1271 protein PANK2 20p13 pantothenate kinase 2 (Hallervorden-Spatz syndrome) RNF24 20p13-p12.1 ring finger protein 24 LOC388783 20 similar to hypothetical protein RPL21P2 20p13 ribosomal protein L21 pseudogene 2 MGC34919 20p13 hypothetical protein MGC34919 SMOX 20p13 spermine oxidase ADRA1D 20p13 adrenergic, alpha-1D-, receptor RPL7AL2 20p13 ribosomal protein L7a like 2 RPS4L2 20p13 ribosomal protein S4-like 2 PRNP 20p12.3 prion protein (p27-30) (Creutzfeld-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia) PRND 20pter-p12 prion protein 2 (dublet) LOC149830 20p13 M8 protein RASSF2 20pter-p12.1 Ras association (RalGDS/AF-6) domain family 2 SLC23A2 5q31.2-q31.3 solute carrier family 23 (nucleobase transporters), member 2 C20orf30 20p13 chromosome 20 open reading frame 30 PCNA 20p12.3 proliferating cell nuclear antigen CDS2 20p13 CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 2 LOC388784 20 similar to dJ680N4.2 (ubiquitin-conjugating enzyme E2D 3 (homologous to yeast UBC4/5)) GPR73L1 20p13 G protein-coupled receptor 73-like 1 LOC388785 20 hypothetical gene supported by AK090863 MGC35023 20p13 hypothetical protein MGC35023 LOC388786 20 LOC388786 LOC388787 20 LOC388787 RPS18P1 20p13 ribosomal protein S18 pseudogene 1 KIAA1434 20p13 hypothetical protein KIAA1434 EIF4EL2 20p13 eukaryotic translation initiation factor 4E-like 2 FLJ25067 20p13 hypothetical protein FLJ25067 CHGB 20p12.3 chromogranin B (secretogranin 1) LOC391230 20 similar to ankyrin repeat domain protein 15; kidney ankyrin repeat-containing protein CGI-09 20p13 CGI-09 protein MCM8 20p12.3 MCM8 minichromosome maintenance deficient 8 (S. cerevisiae) C20orf155 20p13-p12.3 chromosome 20 open reading frame 155 C20orf75 20p13 chromosome 20 open reading frame 75 C20orf42 20p12.3 chromosome 20 open reading frame 42 LOC219414 20p12.3 similar to TAR DNA binding protein LOC149844 20p12.3 NS1-associated protein 1 pseudogene
    RNA
    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
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart   highly
    Digestiveliver   highly
    Endocrineadrenal gland    
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    conjugated sumoylated
    mono polymer homomer , trimer
    HOMOLOGY
    interspecies homolog to murine Pcna
    homolog to C.elegans pcn-1
    Homologene
    FAMILY
  • PCNA family
  • CATEGORY regulatory , DNA associated , antigen
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    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
  • 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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    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
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • 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
  • 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
  • cell & other
    REGULATION
    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
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibition of the PCNA protein-protein interaction can be a new strategy to sensitize cancer cells to chemotherapy
    ANIMAL & CELL MODELS