Protein: P12004

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P12004 (Uniprot) PCNA_HUMAN PCNA Proliferating cell nuclear antigen human No
Uniprot: 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 (PubMed:24939902). 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. more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0006725 cellular aromatic compound metabolic process 239 GO:0007165 signal transduction 308 5.44e-126 5.27e-27
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
79 GO:0007165 signal transduction
93 GO:0034645 cellular macromolecule biosynthetic process
93 GO:0034654 nucleobase-containing compound biosynthetic process
93 GO:0019538 protein metabolic process
93 GO:0051252 regulation of RNA metabolic process
93 GO:0010468 regulation of gene expression
173 GO:0034645 cellular macromolecule biosynthetic process
173 GO:0006464 cellular protein modification process
173 GO:0010467 gene expression
173 GO:0035556 intracellular signal transduction
173 GO:0090304 nucleic acid metabolic process
173 GO:0016310 phosphorylation
173 GO:0031325 positive regulation of cellular metabolic process
173 GO:0010604 positive regulation of macromolecule metabolic process
173 GO:0051173 positive regulation of nitrogen compound metabolic process
173 GO:0031326 regulation of cellular biosynthetic process
173 GO:0019219 regulation of nucleobase-containing compound metabolic process
177 GO:0044267 cellular protein metabolic process
181 GO:0044267 cellular protein metabolic process
181 GO:0010467 gene expression
181 GO:0009059 macromolecule biosynthetic process
181 GO:0090304 nucleic acid metabolic process
181 GO:0060255 regulation of macromolecule metabolic process
181 GO:0007165 signal transduction
196 GO:0034645 cellular macromolecule biosynthetic process
196 GO:0006464 cellular protein modification process
196 GO:0090304 nucleic acid metabolic process
196 GO:0031326 regulation of cellular biosynthetic process
196 GO:0010468 regulation of gene expression
196 GO:0010556 regulation of macromolecule biosynthetic process
196 GO:0007165 signal transduction
239 GO:0006139 nucleobase-containing compound metabolic process
308 GO:0007166 cell surface receptor signaling pathway
308 GO:0071310 cellular response to organic substance
308 GO:0035556 intracellular signal transduction
308 GO:0043085 positive regulation of catalytic activity
308 GO:0031328 positive regulation of cellular biosynthetic process
308 GO:0010604 positive regulation of macromolecule metabolic process
308 GO:0045935 positive regulation of nucleobase-containing compound metabolic process
308 GO:0009967 positive regulation of signal transduction
308 GO:0006468 protein phosphorylation
308 GO:0031399 regulation of protein modification process
308 GO:0006355 regulation of transcription, DNA-templated
500 GO:0007165 signal transduction
536 GO:0010604 positive regulation of macromolecule metabolic process
536 GO:0051173 positive regulation of nitrogen compound metabolic process
536 GO:0019538 protein metabolic process
536 GO:0007165 signal transduction
779 GO:0034645 cellular macromolecule biosynthetic process
779 GO:0090304 nucleic acid metabolic process
779 GO:0034654 nucleobase-containing compound biosynthetic process
779 GO:0060255 regulation of macromolecule metabolic process
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
34 GO:0005634 nucleus
79 GO:0005634 nucleus
93 GO:0005829 cytosol
93 GO:0005634 nucleus
173 GO:0005654 nucleoplasm
177 GO:0005634 nucleus
181 GO:0005829 cytosol
181 GO:0005654 nucleoplasm
196 GO:0005634 nucleus
239 GO:0043232 intracellular non-membrane-bounded organelle
239 GO:0031981 nuclear lumen
289 GO:0005634 nucleus
308 GO:0005829 cytosol
308 GO:0070013 intracellular organelle lumen
308 GO:0044428 nuclear part
308 GO:0005886 plasma membrane
500 GO:0043232 intracellular non-membrane-bounded organelle
500 GO:0070013 intracellular organelle lumen
500 GO:0005634 nucleus
500 GO:0031982 vesicle
536 GO:0005829 cytosol
536 GO:0005634 nucleus
548 GO:0070013 intracellular organelle lumen
548 GO:0005634 nucleus
779 GO:0043232 intracellular non-membrane-bounded organelle
779 GO:0070013 intracellular organelle lumen
779 GO:0044428 nuclear part
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle TAS
GO:0000723 telomere maintenance TAS
GO:0006266 DNA ligation TAS
GO:0006272 leading strand elongation IBA
GO:0006283 transcription-coupled nucleotide-excision repair TAS
GO:0006296 nucleotide-excision repair, DNA incision, 5'-to lesion TAS
GO:0006297 nucleotide-excision repair, DNA gap filling TAS
GO:0006298 mismatch repair TAS
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS
GO:0007507 heart development IEA
GO:0008283 cell proliferation TAS
GO:0016567 protein ubiquitination TAS
GO:0016925 protein sumoylation TAS
GO:0019985 translesion synthesis TAS
GO:0030855 epithelial cell differentiation IEP
GO:0031297 replication fork processing ISS
GO:0032077 positive regulation of deoxyribonuclease activity IDA
GO:0032201 telomere maintenance via semi-conservative replication TAS
GO:0032355 response to estradiol IEA
GO:0033683 nucleotide-excision repair, DNA incision TAS
GO:0034644 cellular response to UV IDA
GO:0042276 error-prone translesion synthesis TAS
GO:0042769 DNA damage response, detection of DNA damage TAS
GO:0044849 estrous cycle IEA
GO:0045739 positive regulation of DNA repair IMP
GO:0045740 positive regulation of DNA replication IMP
GO:0046686 response to cadmium ion IEA
GO:0070301 cellular response to hydrogen peroxide IEA
GO:0070987 error-free translesion synthesis TAS
GO:0071548 response to dexamethasone IEA
GO:0097421 liver regeneration IEA
GO:1902065 response to L-glutamate IEA
GO:1902990 mitotic telomere maintenance via semi-conservative replication ISS
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0000784 nuclear chromosome, telomeric region IDA
GO:0005634 nucleus IDA
GO:0005654 nucleoplasm TAS
GO:0005657 replication fork IDA
GO:0005663 DNA replication factor C complex TAS
GO:0005813 centrosome IDA
GO:0016604 nuclear body IDA
GO:0030894 replisome TAS
GO:0043596 nuclear replication fork IDA
GO:0043626 PCNA complex IDA
GO:0070062 extracellular exosome IDA
GO:0070557 PCNA-p21 complex IDA
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005634 nucleus GO:0070062 extracellular exosome 6.30e-13 4.54e-26
GO:0005654 nucleoplasm GO:0070062 extracellular exosome 3.37e-20 1.23e-35
GO:0016604 nuclear body GO:0070062 extracellular exosome 1.52e-08 2.57e-155
PMID Article Title
2565339 Structure of the human gene for the proliferating cell nuclear antigen.
2882422 The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro.
2882507 Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins.
8861913 Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA.
9302295 Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1.
9305916 The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21.
9566895 Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase.
11376153 Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen.
11595739 Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication through a conserved p21(Cip1)-like PCNA-binding motif present in the third subunit of human DNA polymerase delta.
11780052 The DNA sequence and comparative analysis of human chromosome 20.
11784855 Stimulation of DNA synthesis activity of human DNA polymerase kappa by PCNA.
12522211 Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen.
12786946 Terminal deoxynucleotidyltransferase forms a ternary complex with a novel chromatin remodeling protein with 82 kDa and core histone.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
15149598 Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage.
15225546 A defined human system that supports bidirectional mismatch-provoked excision.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15543136 The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci.
15616578 Structural basis for recruitment of human flap endonuclease 1 to PCNA.
16510448 Functional roles of p12, the fourth subunit of human DNA polymerase delta.
16949367 A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.
17108083 Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen.
17115032 Tyrosine phosphorylation controls PCNA function through protein stability.
17130289 Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination.
18316726 Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination.
18499658 Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1.
18703516 CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation.
18719106 Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks.
18794347 PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex.
18948756 PCNA is ubiquitinated by RNF8.
19419956 Proliferating cell nuclear antigen is protected from degradation by forming a complex with MutT Homolog2.
19443450 Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage.
19608861 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19995904 DNA polymerase POLN participates in cross-link repair and homologous recombination.
20129063 CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis.
20227374 Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.
20457750 Metnase promotes restart and repair of stalled and collapsed replication forks.
21269460 Initial characterization of the human central proteome.
21549307 Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
21628590 Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate.
22148433 Phosphorylation of the p68 subunit of Pol delta acts as a molecular switch to regulate its interaction with PCNA.
22153967 Inhibition of homologous recombination by the PCNA-interacting protein PARI.
22634751 Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome.
22681887 Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response.
22704558 Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress.
22705370 The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress.
22759634 ZRANB3 is a structure-specific ATP-dependent endonuclease involved in replication stress response.
23000965 Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
23677613 The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)-mediated proteolysis in human cells.
23711367 A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and Nod2-mediated inflammatory responses.
24115439 RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24561620 Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components.
24911150 Hypomorphic PCNA mutation underlies a human DNA repair disorder.
24939902 CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis.
25114211 Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.
25732820 Human C6orf211 encodes Armt1, a protein carboxyl methyltransferase that targets PCNA and is linked to the DNA damage response.
25755297 System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.
25772364 SUMO-2 orchestrates chromatin modifiers in response to DNA damage.
25944712 N-terminome analysis of the human mitochondrial proteome.
27906959 PCNA-dependent cleavage and degradation of SDE2 regulates response to replication stress.
28112733 Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.
28191891 Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.
OMIM ID Disease Name
615919 Ataxia-telangiectasia-like disorder 2
Domain Name Domain ID Source
WMHUET A27445 PIR
Pr_cel_nuc_antig IPR000730 InterPro
Pr_cel_nuc_antig_N IPR022648 InterPro
Pr_cel_nuc_antig_C IPR022649 InterPro
Pr_cel_nuc_antig_CS IPR022659 InterPro
DNApol_clamp_arch MF_00317 HAMAP
PCNA_N PF00705 Pfam
PCNA_C PF02747 Pfam
PCNACYCLIN PR00339 PRINTS
PCNA_2 PS00293 PROSITE
PCNA_1 PS01251 PROSITE
PTHR11352:SF0 PTHR11352:SF0 PANTHER
pcna TIGR00590 TIGRFAMs