ID:PCNA_HUMAN DESCRIPTION: RecName: Full=Proliferating cell nuclear antigen; Short=PCNA; AltName: Full=Cyclin; FUNCTION: 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. SUBUNIT: 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 (By similarity). 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/PARI. 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). INTERACTION: Self; NbExp=4; IntAct=EBI-358311, EBI-358311; P38936:CDKN1A; NbExp=4; IntAct=EBI-358311, EBI-375077; P42771:CDKN2A; NbExp=8; IntAct=EBI-358311, EBI-375053; Q13111:CHAF1A; NbExp=2; IntAct=EBI-358311, EBI-1020839; P39748:FEN1; NbExp=4; IntAct=EBI-358311, EBI-707816; Q9Z111:Gadd45g (xeno); NbExp=9; IntAct=EBI-358311, EBI-1173616; P28340:POLD1; NbExp=2; IntAct=EBI-358311, EBI-716569; Q15054:POLD3; NbExp=4; IntAct=EBI-358311, EBI-864956; Q9HCU8:POLD4; NbExp=4; IntAct=EBI-358311, EBI-864968; SUBCELLULAR LOCATION: Nucleus. 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. PTM: 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. PTM: Acetylated in response to UV irradiation. Acetylation disrupts interaction with NUDT15 and promotes degradation. PTM: Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA. MISCELLANEOUS: Antibodies against PCNA are present in sera from patients with systemic lupus erythematosus. SIMILARITY: Belongs to the PCNA family. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/pcna/"; WEB RESOURCE: Name=Wikipedia; Note=PCNA entry; URL="http://en.wikipedia.org/wiki/PCNA";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P12004
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000701 purine-specific mismatch base pair DNA N-glycosylase activity GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003684 damaged DNA binding GO:0005515 protein binding GO:0019899 enzyme binding GO:0030331 estrogen receptor binding GO:0030337 DNA polymerase processivity factor activity GO:0030971 receptor tyrosine kinase binding GO:0032139 dinucleotide insertion or deletion binding GO:0032405 MutLalpha complex binding GO:0035035 histone acetyltransferase binding GO:0042802 identical protein binding GO:0070182 DNA polymerase binding
Biological Process: GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle GO:0000723 telomere maintenance GO:0006260 DNA replication GO:0006272 leading strand elongation GO:0006275 regulation of DNA replication GO:0006281 DNA repair GO:0006283 transcription-coupled nucleotide-excision repair GO:0006296 nucleotide-excision repair, DNA incision, 5'-to lesion GO:0006297 nucleotide-excision repair, DNA gap filling GO:0006298 mismatch repair GO:0006974 cellular response to DNA damage stimulus GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0006979 response to oxidative stress GO:0007507 heart development GO:0008283 cell proliferation GO:0016567 protein ubiquitination GO:0019985 translesion synthesis GO:0030855 epithelial cell differentiation GO:0031297 replication fork processing GO:0032077 positive regulation of deoxyribonuclease activity GO:0032201 telomere maintenance via semi-conservative replication GO:0032355 response to estradiol GO:0033683 nucleotide-excision repair, DNA incision GO:0033993 response to lipid GO:0034644 cellular response to UV GO:0042276 error-prone translesion synthesis GO:0042769 DNA damage response, detection of DNA damage GO:0044849 estrous cycle GO:0045739 positive regulation of DNA repair GO:0045740 positive regulation of DNA replication GO:0046686 response to cadmium ion GO:0070301 cellular response to hydrogen peroxide GO:0070987 error-free translesion synthesis GO:0071548 response to dexamethasone GO:0097421 liver regeneration GO:1902065 response to L-glutamate GO:1902990 mitotic telomere maintenance via semi-conservative replication
M15796 - Human cyclin protein gene, complete cds. BC000491 - Homo sapiens proliferating cell nuclear antigen, mRNA (cDNA clone MGC:8367 IMAGE:2820036), complete cds. BC062439 - Homo sapiens proliferating cell nuclear antigen, mRNA (cDNA clone MGC:72035 IMAGE:4102284), complete cds. DM110844 - Novel Cancer Marker and Use Thereof. JD052176 - Sequence 33200 from Patent EP1572962. JD237483 - Sequence 218507 from Patent EP1572962. DQ891403 - Synthetic construct clone IMAGE:100004033; FLH176609.01X; RZPDo839F04122D proliferating cell nuclear antigen (PCNA) gene, encodes complete protein. CR536501 - Homo sapiens full open reading frame cDNA clone RZPDo834B0222D for gene PCNA, proliferating cell nuclear antigen; complete cds, incl. stopcodon. AK313286 - Homo sapiens cDNA, FLJ93798, Homo sapiens proliferating cell nuclear antigen (PCNA), mRNA. KJ891758 - Synthetic construct Homo sapiens clone ccsbBroadEn_01152 PCNA gene, encodes complete protein. DQ894581 - Synthetic construct Homo sapiens clone IMAGE:100009041; FLH176605.01L; RZPDo839F04121D proliferating cell nuclear antigen (PCNA) gene, encodes complete protein. CR541799 - Homo sapiens full open reading frame cDNA clone RZPDo834C1031D for gene PCNA, proliferating cell nuclear antigen; complete cds, without stopcodon. AB464071 - Synthetic construct DNA, clone: pF1KB6335, Homo sapiens PCNA gene for proliferating cell nuclear antigen, without stop codon, in Flexi system. AK300558 - Homo sapiens cDNA FLJ50224 complete cds, highly similar to Proliferating cell nuclear antigen. AK311014 - Homo sapiens cDNA, FLJ18056. JD235110 - Sequence 216134 from Patent EP1572962. D28458 - Homo sapiens mRNA for proliferating cell nuclear antigen, 5'UTR region. JD175158 - Sequence 156182 from Patent EP1572962. M29310 - Human proliferating cell nuclear antigen cyclin mRNA, 5' region.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_p53Pathway - p53 Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P12004 (Reactome details) participates in the following event(s):
R-HSA-4615910 SUMOylation of PCNA with SUMO1 R-HSA-69063 Loading of PCNA - Sliding Clamp Formation R-HSA-174439 Loading of PCNA - Sliding Clamp Formation on the C-strand of the telomere R-HSA-5358510 MSH2:MSH6 recruits MLH1:PMS2 to mismatch and interacts with PCNA R-HSA-5358519 MSH2:MSH3 recruits MLH1:PMS2 to mismatch and interacts with PCNA R-HSA-6791109 GADD45A binds PCNA R-HSA-176702 Disassociation of Processive Complex and Completed Telomere End R-HSA-8943007 SHPRH binds monoUb-K164-PCNA, RAD6:RAD18, UBE2V2:Ub:UBE2N R-HSA-8943041 HLTF binds monoUb-K164-PCNA, RAD6:RAD18, UBE2V2:Ub:UBE2N R-HSA-69074 Formation of Processive Complex R-HSA-69068 RFC dissociates after sliding clamp formation R-HSA-174445 RPA binds to the Flap on the C-strand R-HSA-174438 Formation of the Flap Intermediate on the C-strand R-HSA-174456 Joining of adjacent Okazaki fragments of the C-strand R-HSA-174446 Removal of remaining Flap from the C-strand R-HSA-174444 Formation of C-strand Okazaki fragments R-HSA-174441 Removal of RNA primer and dissociation of RPA and Dna2 from the C-strand R-HSA-174447 RFC dissociates after sliding clamp formation on the C-strand of the telomere R-HSA-174448 Formation of Processive Complex on the C-strand of the telomere R-HSA-5358518 MLH1:PMS2 makes single strand incision near 1-2 base mismatch R-HSA-5358545 EXO1 interacts with MSH2:MSH3 (MutSbeta) and MLH1:PMS2 (MutLalpha) R-HSA-5358512 MLH1:PMS2 makes single strand incision near insertion/deletion loop of 2 bases or more R-HSA-5358597 EXO1 interacts with MSH2:MSH6 (MutSalpha) and MLH1:PMS2 (MutLalpha) R-HSA-110364 PCNA:POLD,POLE:RPA:RFC and FEN1 bind APEX1 R-HSA-5651992 PCNA-containing replication complex binds damaged dsDNA R-HSA-5651809 LIG1, APEX1 and PCNA:POLD,POLE:RPA:RFC dissociate from repaired DNA R-HSA-5653840 POLD,POLE complete replication of damaged DNA after TLS R-HSA-5653838 POLD,POLE binds deISGylated PCNA after TLS R-HSA-5653786 USP43 deISGylates ISG:K164,ISG:K168-PCNA R-HSA-5655466 USP1:WDR48 deubiquitinates monoUb:K164-PCNA R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-5653766 USP10 binds monoUb:K164,ISG:K164,ISG:K168-PCNA R-HSA-5653754 UBE2L6:TRIM25 ISGylates monoUb:K164-PCNA R-HSA-5653780 USP43 binds ISG:K164,ISG:K168-PCNA R-HSA-5653770 USP10 deubiquitinates monoUb:K164,ISG:K164,ISG:K168-PCNA R-HSA-69116 Formation of Okazaki fragments R-HSA-174451 Recruitment of Dna2 endonuclease to the C strand R-HSA-110368 POLD,POLE-mediated DNA strand displacement synthesis R-HSA-110371 LIG1 binds APEX1 and PCNA at SSB R-HSA-110363 FEN1 bound to PCNA and APEX1 cleaves flap ssDNA R-HSA-5651805 LIG1 bound to APEX1 and PCNA ligates SSB R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA R-HSA-5655481 USP1:WDR48 binds monoUb:K164-PCNA R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA R-HSA-110307 REV1 binds AP-dsDNA R-HSA-110311 POLZ extends translesion synthesis R-HSA-5653756 TRIM25 binds monoUb:164-PCNA R-HSA-110316 POLH binds monoUb:K164-PCNA at damaged TT-CPD-DNA template R-HSA-5654986 SPRTN binds monoUb:K164-PCNA associated with POLH R-HSA-110319 Elongation by POLH R-HSA-5654989 SPRTN:VCP-mediated release of POLH from monoUb:K164-PCNA R-HSA-5655835 POLK forms a quaternary complex with REV1 and POLZ on damaged DNA template R-HSA-5656105 POLI simultaneously binds REV1 and monoUb:K164-PCNA at damaged DNA R-HSA-110317 Insertion of correct bases opposite the lesion by POLH R-HSA-69127 Formation of the Flap Intermediate R-HSA-69152 Removal of remaining Flap R-HSA-69144 Removal of RNA primer and dissociation of RPA and Dna2 R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5690997 Ligation of newly synthesized repair patch to incised DNA in GG-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-5652151 REV1 recruits POLZ to (AP:Cyt)-DNA Template R-HSA-110308 REV1 inserts dCMP opposite to AP sites in DNA R-HSA-5654985 SPRTN recruits VCP to monoUb:K164-PCNA associated with POLH R-HSA-5655892 POLK incorporates dNMP opposite to damaged DNA base R-HSA-5655965 POLK and POLZ cooperate in elongation of mispaired primer termini R-HSA-5656148 POLI incorporates dNMP opposite to damaged DNA base R-HSA-5656158 POLZ elongates POLI-incorporated dNMP R-HSA-69140 RPA binds to the Flap R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-5691001 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in GG-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-69142 Recruitment of Dna2 endonuclease R-HSA-4615885 SUMOylation of DNA replication proteins R-HSA-539107 Activation of E2F1 target genes at G1/S R-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex R-HSA-69091 Polymerase switching R-HSA-174411 Polymerase switching on the C-strand of the telomere R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-69205 G1/S-Specific Transcription R-HSA-1538133 G0 and Early G1 R-HSA-174437 Removal of the Flap Intermediate from the C-strand R-HSA-174414 Processive synthesis on the C-strand of the telomere R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex R-HSA-5656169 Termination of translesion DNA synthesis R-HSA-5696400 Dual Incision in GG-NER R-HSA-6782135 Dual incision in TC-NER R-HSA-69109 Leading Strand Synthesis R-HSA-69186 Lagging Strand Synthesis R-HSA-5358508 Mismatch Repair R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes R-HSA-180786 Extension of Telomeres R-HSA-8852135 Protein ubiquitination R-HSA-2990846 SUMOylation R-HSA-69206 G1/S Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69183 Processive synthesis on the lagging strand R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-73893 DNA Damage Bypass R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-69190 DNA strand elongation R-HSA-73894 DNA Repair R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-157579 Telomere Maintenance R-HSA-110312 Translesion synthesis by REV1 R-HSA-110320 Translesion Synthesis by POLH R-HSA-5655862 Translesion synthesis by POLK R-HSA-5656121 Translesion synthesis by POLI R-HSA-597592 Post-translational protein modification R-HSA-69278 Cell Cycle (Mitotic) R-HSA-69166 Removal of the Flap Intermediate R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-73933 Resolution of Abasic Sites (AP sites) R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-5696398 Nucleotide Excision Repair R-HSA-69239 Synthesis of DNA R-HSA-212436 Generic Transcription Pathway R-HSA-73886 Chromosome Maintenance R-HSA-392499 Metabolism of proteins R-HSA-1640170 Cell Cycle R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-73884 Base Excision Repair R-HSA-69242 S Phase R-HSA-69306 DNA Replication R-HSA-73857 RNA Polymerase II Transcription R-HSA-5693538 Homology Directed Repair R-HSA-74160 Gene expression (Transcription) R-HSA-5693532 DNA Double-Strand Break Repair
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
