P17918 (PCNA_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 142. History...
Names and origin
|Protein names||Recommended name:|
Proliferating cell nuclear antigen
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||261 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 By similarity. HAMAP-Rule MF_00317
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. 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. Ref.5 Ref.6 Ref.9
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. Ref.9
Induced in IL2-stimulated proliferating T-lymphocytes. HAMAP-Rule MF_00317
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 By similarity. HAMAP-Rule MF_00317
Acetylated in response to UV irradiation. Acetylation disrupts interaction with NUDT15 and promotes degradation By similarity. HAMAP-Rule MF_00317
Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA By similarity. Ref.7
Belongs to the PCNA family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 261||261||Proliferating cell nuclear antigen HAMAP-Rule MF_00317||PRO_0000149160|
|DNA binding||61 – 80||20||Potential|
Amino acid modifications
|Modified residue||14||1||N6-acetyllysine By similarity|
|Modified residue||77||1||N6-acetyllysine By similarity|
|Modified residue||80||1||N6-acetyllysine Ref.8|
|Modified residue||211||1||Phosphotyrosine; by EGFR Ref.7|
|Modified residue||248||1||N6-acetyllysine By similarity|
|Cross-link||164||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Sequence conflict||3 – 5||3||EAR → LES no nucleotide entry Ref.4|
|Sequence conflict||67||1||A → T in CAA37243. Ref.2|
|||"Nucleotide sequence of murine PCNA: interspecies comparison of the cDNA and the 5' flanking region of the gene."|
Shipman-Appasamy P.M., Cohen K.S., Prystowsky M.B.
DNA Seq. 2:181-191(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lymphoid tissue.
|||"Molecular cloning and structural analysis of mouse gene and pseudogenes for proliferating cell nuclear antigen."|
Yamaguchi M., Hayashi Y., Hirose F., Matsuoka S., Moriuchi T., Shiroishi T., Moriwaki K., Matsukage A.
Nucleic Acids Res. 19:2403-2410(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary gland.
|||"Cyclin mRNA and protein expression in recombinant interleukin 2-stimulated cloned murine T lymphocytes."|
Shipman P.M., Sabath D.E., Fischer A.H., Comber P.G., Sullivan K., Tan E.M., Prystowsky M.B.
J. Cell. Biochem. 38:189-198(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-42.
|||"The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34."|
Brown S.M., MacLean A.R., McKie E.A., Harland J.
J. Virol. 71:9442-9449(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPP1R15A AND HHV-1 ICP34.5.
|||"Characterization of the genomic structure and expression of the mouse Apex2 gene."|
Ide Y., Tsuchimoto D., Tominaga Y., Iwamoto Y., Nakabeppu Y.
Genomics 81:47-57(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APEX2.
|||"Tyrosine phosphorylation controls PCNA function through protein stability."|
Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C.
Nat. Cell Biol. 8:1359-1368(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-211.
|||"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."|
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-80, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
|||"RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication."|
Vannier J.B., Sandhu S., Petalcorin M.I., Wu X., Nabi Z., Ding H., Boulton S.J.
Science 342:239-242(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RTEL1, SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|X53068 mRNA. Translation: CAA37243.1.|
X57800 Genomic DNA. Translation: CAA40938.1.
BC005778 mRNA. Translation: AAH05778.1.
BC010343 mRNA. Translation: AAH10343.1.
|PIR||WMMS. S15703. |
|RefSeq||NP_035175.1. NM_011045.2. |
3D structure databases
|SMR||P17918. Positions 1-257. |
Protein-protein interaction databases
|BioGrid||202049. 20 interactions.|
|IntAct||P17918. 9 interactions.|
2D gel databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000028817; ENSMUSP00000028817; ENSMUSG00000027342. |
|UCSC||uc008mml.1. mouse. |
|MGI||MGI:97503. Pcna. |
Gene expression databases
Family and domain databases
|HAMAP||MF_00317. DNApol_clamp_arch. |
|InterPro||IPR000730. Pr_cel_nuc_antig. |
|PANTHER||PTHR11352. PTHR11352. 1 hit. |
|Pfam||PF02747. PCNA_C. 1 hit. |
PF00705. PCNA_N. 1 hit.
|PRINTS||PR00339. PCNACYCLIN. |
|TIGRFAMs||TIGR00590. pcna. 1 hit. |
|PROSITE||PS01251. PCNA_1. 1 hit. |
PS00293. PCNA_2. 1 hit.
|Accession||Primary (citable) accession number: P17918|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|