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MGP002216

UniProt Annotations

Entry Information
Gene Nameproliferating cell nuclear antigen
Protein EntryPCNA_HUMAN
UniProt IDP12004
SpeciesHuman
Comments
Comment typeDescription
DiseaseAtaxia-telangiectasia-like disorder 2 (ATLD2) [MIM:615919]: A neurodegenerative disorder due to defects in DNA excision repair. ATLD2 is characterized by developmental delay, ataxia, sensorineural hearing loss, short stature, cutaneous and ocular telangiectasia, and photosensitivity. {ECO:0000269|PubMed:24911150}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionAuxiliary 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. {ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19443450}.
InteractionSelf; NbExp=4; IntAct=EBI-358311, EBI-358311; Q8TE30:-; NbExp=6; IntAct=EBI-358311, EBI-8874509; P04075:ALDOA; NbExp=3; IntAct=EBI-358311, EBI-709613; P38936:CDKN1A; NbExp=6; IntAct=EBI-358311, EBI-375077; P42771:CDKN2A; NbExp=8; IntAct=EBI-358311, EBI-375053; Q9H211:CDT1; NbExp=2; IntAct=EBI-358311, EBI-456953; Q13111:CHAF1A; NbExp=3; IntAct=EBI-358311, EBI-1020839; P06733:ENO1; NbExp=3; IntAct=EBI-358311, EBI-353877; P39748:FEN1; NbExp=4; IntAct=EBI-358311, EBI-707816; Q9Z111:Gadd45g (xeno); NbExp=9; IntAct=EBI-358311, EBI-1173616; P04406:GAPDH; NbExp=3; IntAct=EBI-358311, EBI-354056; Q9H160:ING2; NbExp=3; IntAct=EBI-358311, EBI-389787; P18669:PGAM1; NbExp=2; IntAct=EBI-358311, EBI-717905; 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; P60174:TPI1; NbExp=2; IntAct=EBI-358311, EBI-717475;
MiscellaneousAntibodies against PCNA are present in sera from patients with systemic lupus erythematosus.
PtmAcetylated in response to UV irradiation. Acetylation disrupts interaction with NUDT15 and promotes degradation. {ECO:0000269|PubMed:19419956, ECO:0000269|PubMed:19608861}.
PtmFollowing 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. {ECO:0000269|PubMed:15149598, ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:22153967}.
PtmPhosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA. {ECO:0000269|PubMed:17115032}.
SimilarityBelongs to the PCNA family. {ECO:0000305}.
Subcellular LocationNucleus {ECO:0000269|PubMed:24115439}. 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.
SubunitHomotrimer (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. Interacts with LIG1. Interacts with SETMAR. Interacts with ANKRD17. {ECO:0000250, ECO:0000269|PubMed:11376153, ECO:0000269|PubMed:11784855, ECO:0000269|PubMed:12522211, ECO:0000269|PubMed:12786946, ECO:0000269|PubMed:15149598, ECO:0000269|PubMed:15225546, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:15616578, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17130289, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18499658, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:19419956, ECO:0000269|PubMed:19443450, ECO:0000269|PubMed:20457750, ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:21628590, ECO:0000269|PubMed:22153967, ECO:0000269|PubMed:22634751, ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:22704558, ECO:0000269|PubMed:22705370, ECO:0000269|PubMed:22759634, ECO:0000269|PubMed:23000965, ECO:0000269|PubMed:23711367, ECO:0000269|PubMed:24115439, ECO:0000269|PubMed:24561620, ECO:0000269|PubMed:24911150, ECO:0000269|PubMed:9302295, ECO:0000269|PubMed:9305916, ECO:0000269|PubMed:9566895}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PCNAID41670ch20p12.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/pcna/";
Web ResourceName=Wikipedia; Note=PCNA entry; URL="http://en.wikipedia.org/wiki/PCNA";
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