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P12004 (PCNA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proliferating cell nuclear antigen

Short name=PCNA
Alternative name(s):
Cyclin
Gene names
Name:PCNA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length261 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.29 Ref.31

Subunit structure

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.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46

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. Ref.45

Post-translational modification

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. Ref.38

Acetylated in response to UV irradiation. Acetylation disrupts interaction with NUDT15 and promotes degradation. Ref.32

Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA. Ref.23

Miscellaneous

Antibodies against PCNA are present in sera from patients with systemic lupus erythematosus.

Sequence similarities

Belongs to the PCNA family.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
DNA replication
   Cellular componentNucleus
   LigandDNA-binding
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Non-traceable author statement PubMed 15504738. Source: UniProtKB

DNA replication

Non-traceable author statement PubMed 15504738. Source: UniProtKB

DNA strand elongation involved in DNA replication

Traceable author statement. Source: Reactome

G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

base-excision repair

Traceable author statement. Source: Reactome

cell proliferation

Traceable author statement Ref.2. Source: ProtInc

epithelial cell differentiation

Inferred from expression pattern PubMed 21492153. Source: UniProt

heart development

Inferred from electronic annotation. Source: Ensembl

leading strand elongation

Inferred from Biological aspect of Ancestor. Source: RefGenome

mismatch repair

Inferred from direct assay PubMed 11005803. Source: BHF-UCL

mitotic cell cycle

Traceable author statement. Source: Reactome

nucleotide-excision repair

Traceable author statement. Source: Reactome

nucleotide-excision repair, DNA gap filling

Traceable author statement. Source: Reactome

phosphatidylinositol-mediated signaling

Non-traceable author statement PubMed 15504738. Source: UniProtKB

positive regulation of deoxyribonuclease activity

Inferred from direct assay Ref.29. Source: UniProtKB

regulation of DNA replication

Inferred from electronic annotation. Source: InterPro

regulation of transcription involved in G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to lipid

Inferred from electronic annotation. Source: Ensembl

telomere maintenance

Traceable author statement. Source: Reactome

telomere maintenance via recombination

Traceable author statement. Source: Reactome

telomere maintenance via semi-conservative replication

Traceable author statement. Source: Reactome

transcription-coupled nucleotide-excision repair

Traceable author statement. Source: Reactome

translesion synthesis

Inferred from direct assay Ref.34. Source: UniProtKB

   Cellular_componentDNA replication factor C complex

Traceable author statement Ref.2. Source: UniProtKB

PCNA complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

PCNA-p21 complex

Inferred from direct assay Ref.26. Source: UniProtKB

centrosome

Inferred from direct assay PubMed 18331714. Source: MGI

cytoplasm

Inferred from direct assay. Source: HPA

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

nuclear replication fork

Inferred from direct assay Ref.19. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionDNA polymerase binding

Inferred from physical interaction PubMed 19995904. Source: UniProt

DNA polymerase processivity factor activity

Inferred from electronic annotation. Source: InterPro

MutLalpha complex binding

Inferred from direct assay PubMed 11005803. Source: HGNC

dinucleotide insertion or deletion binding

Inferred from direct assay PubMed 11005803. Source: BHF-UCL

identical protein binding

Inferred from physical interaction PubMed 15805117. Source: IntAct

protein binding

Inferred from physical interaction Ref.17PubMed 15358233PubMed 15550930Ref.27PubMed 19505873Ref.36Ref.37Ref.38Ref.44Ref.39Ref.43Ref.41Ref.40PubMed 22894931PubMed 22902628Ref.42PubMed 23042605PubMed 23042607Ref.46Ref.10. Source: UniProtKB

purine-specific mismatch base pair DNA N-glycosylase activity

Inferred from direct assay PubMed 11005803. Source: BHF-UCL

receptor tyrosine kinase binding

Inferred from physical interaction Ref.23. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 261261Proliferating cell nuclear antigen HAMAP-Rule MF_00317
PRO_0000149158

Regions

DNA binding61 – 8020 Potential
Region7 – 10094Interaction with NUDT15 HAMAP-Rule MF_00317

Amino acid modifications

Modified residue141N6-acetyllysine Ref.32
Modified residue771N6-acetyllysine Ref.33
Modified residue801N6-acetyllysine Ref.33
Modified residue2111Phosphotyrosine; by EGFR Ref.23
Modified residue2481N6-acetyllysine Ref.33
Cross-link164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.21 Ref.24

Experimental info

Mutagenesis1641K → R: Abolishes ubiquitination. No effect on interaction with SHPRH. Ref.21 Ref.24 Ref.31 Ref.34
Mutagenesis2111Y → F: Alters chromatin-associated PCNA stability and its function in DNA replication and repair. Ref.23

Secondary structure

.................................................. 261
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P12004 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: E6F08E7EDBC48B00

FASTA26128,769
        10         20         30         40         50         60 
MFEARLVQGS ILKKVLEALK DLINEACWDI SSSGVNLQSM DSSHVSLVQL TLRSEGFDTY 

        70         80         90        100        110        120 
RCDRNLAMGV NLTSMSKILK CAGNEDIITL RAEDNADTLA LVFEAPNQEK VSDYEMKLMD 

       130        140        150        160        170        180 
LDVEQLGIPE QEYSCVVKMP SGEFARICRD LSHIGDAVVI SCAKDGVKFS ASGELGNGNI 

       190        200        210        220        230        240 
KLSQTSNVDK EEEAVTIEMN EPVQLTFALR YLNFFTKATP LSSTVTLSMS ADVPLVVEYK 

       250        260 
IADMGHLKYY LAPKIEDEEG S 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins."
Almendral J.M., Huebsch D., Blundell P.A., Macdonald-Bravo H., Bravo R.
Proc. Natl. Acad. Sci. U.S.A. 84:1575-1579(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of the human gene for the proliferating cell nuclear antigen."
Travali S., Ku D.H., Rizzo M.G., Ottavio L., Baserga R., Calabretta B.
J. Biol. Chem. 264:7466-7472(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]NIEHS SNPs program
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skeletal muscle.
[5]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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: Bone marrow and Lung.
[8]"The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro."
Prelich G., Kostura M., Marshak D.R., Mathews M.B., Stillman B.
Nature 326:471-475(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-26.
[9]Lubec G., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 169-181, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Fetal brain cortex.
[10]"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."
Gary R., Ludwig D.L., Cornelius H.L., MacInnes M.A., Park M.S.
J. Biol. Chem. 272:24522-24529(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ERCC5/XPG.
[11]"Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1."
Chuang L.S.-H., Ian H.-I., Koh T.-W., Ng H.-H., Xu G., Li B.F.L.
Science 277:1996-2000(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNMT1.
[12]"Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase."
Saha P., Chen J., Thome K.C., Lawlis S.J., Hou Z.H., Hendricks M., Parvin J.D., Dutta A.
Mol. Cell. Biol. 18:2758-2767(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDC6.
[13]"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."
Tsuchimoto D., Sakai Y., Sakumi K., Nishioka K., Sasaki M., Fujiwara T., Nakabeppu Y.
Nucleic Acids Res. 29:2349-2360(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APEX2.
[14]"Stimulation of DNA synthesis activity of human DNA polymerase kappa by PCNA."
Haracska L., Unk I., Johnson R.E., Phillips B.B., Hurwitz J., Prakash L., Prakash S.
Mol. Cell. Biol. 22:784-791(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH POLK.
[15]"Terminal deoxynucleotidyltransferase forms a ternary complex with a novel chromatin remodeling protein with 82 kDa and core histone."
Fujita K., Shimazaki N., Ohta Y., Kubota T., Ibe S., Toji S., Tamai K., Fujisaki S., Hayano T., Koiwai O.
Genes Cells 8:559-571(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNTTIP2.
[16]"Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen."
Liu L., Rodriguez-Belmonte E.M., Mazloum N., Xie B., Lee M.Y.W.T.
J. Biol. Chem. 278:10041-10047(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH POLDIP2.
Tissue: Placenta.
[17]"A defined human system that supports bidirectional mismatch-provoked excision."
Dzantiev L., Constantin N., Genschel J., Iyer R.R., Burgers P.M., Modrich P.
Mol. Cell 15:31-41(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXO1.
[18]"Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage."
Kannouche P.L., Wing J., Lehmann A.R.
Mol. Cell 14:491-500(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH POLH.
[19]"The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci."
Poot R.A., Bozhenok L., van den Berg D.L.C., Steffensen S., Ferreira F., Grimaldi M., Gilbert N., Ferreira J., Varga-Weisz P.D.
Nat. Cell Biol. 6:1236-1244(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAZ1B.
[20]"Functional roles of p12, the fourth subunit of human DNA polymerase delta."
Li H., Xie B., Zhou Y., Rahmeh A., Trusa S., Zhang S., Gao Y., Lee E.Y., Lee M.Y.
J. Biol. Chem. 281:14748-14755(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH POLD1; POLD3 AND POLD4.
[21]"Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination."
Motegi A., Sood R., Moinova H., Markowitz S.D., Liu P.P., Myung K.
J. Cell Biol. 175:703-708(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SHPRH, UBIQUITINATION AT LYS-164, MUTAGENESIS OF LYS-164.
[22]"A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1."
Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.
Mol. Cell 23:709-721(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDT1.
[23]"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 BY EGFR, MUTAGENESIS OF TYR-211, INTERACTION WITH EGFR.
[24]"Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen."
Unk I., Hajdu I., Fatyol K., Szakal B., Blastyak A., Bermudez V., Hurwitz J., Prakash L., Prakash S., Haracska L.
Proc. Natl. Acad. Sci. U.S.A. 103:18107-18112(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-164, MUTAGENESIS OF LYS-164.
[25]"PCNA is ubiquitinated by RNF8."
Zhang S., Chea J., Meng X., Zhou Y., Lee E.Y.C., Lee M.Y.W.T.
Cell Cycle 7:3399-3404(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[26]"PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex."
Abbas T., Sivaprasad U., Terai K., Amador V., Pagano M., Dutta A.
Genes Dev. 22:2496-2506(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1A.
[27]"Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1."
Farina A., Shin J.H., Kim D.H., Bermudez V.P., Kelman Z., Seo Y.S., Hurwitz J.
J. Biol. Chem. 283:20925-20936(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX11.
[28]"CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation."
Nishitani H., Shiomi Y., Iida H., Michishita M., Takami T., Tsurimoto T.
J. Biol. Chem. 283:29045-29052(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1A.
[29]"Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage."
Burkovics P., Hajdu I., Szukacsov V., Unk I., Haracska L.
Nucleic Acids Res. 37:4247-4255(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH APEX2.
[30]"Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination."
Unk I., Hajdu I., Fatyol K., Hurwitz J., Yoon J.-H., Prakash L., Prakash S., Haracska L.
Proc. Natl. Acad. Sci. U.S.A. 105:3768-3773(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH HLTF.
[31]"Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks."
Motegi A., Liaw H.-J., Lee K.-Y., Roest H.P., Maas A., Wu X., Moinova H., Markowitz S.D., Ding H., Hoeijmakers J.H.J., Myung K.
Proc. Natl. Acad. Sci. U.S.A. 105:12411-12416(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, FUNCTION, INTERACTION WITH HLTF AND SHPRH, MUTAGENESIS OF LYS-164.
[32]"Proliferating cell nuclear antigen is protected from degradation by forming a complex with MutT Homolog2."
Yu Y., Cai J.-P., Tu B., Wu L., Zhao Y., Liu X., Li L., McNutt M.A., Feng J., He Q., Yang Y., Wang H., Sekiguchi M., Zhu W.-G.
J. Biol. Chem. 284:19310-19320(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NUDT15, ACETYLATION AT LYS-14.
[33]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-77; LYS-80 AND LYS-248, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis."
Terai K., Abbas T., Jazaeri A.A., Dutta A.
Mol. Cell 37:143-149(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, MUTAGENESIS OF LYS-164.
[35]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]"Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1."
Rowbotham S.P., Barki L., Neves-Costa A., Santos F., Dean W., Hawkes N., Choudhary P., Will W.R., Webster J., Oxley D., Green C.M., Varga-Weisz P., Mermoud J.E.
Mol. Cell 42:285-296(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMARCAD1.
[37]"Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate."
Emanuele M.J., Ciccia A., Elia A.E., Elledge S.J.
Proc. Natl. Acad. Sci. U.S.A. 108:9845-9850(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KIAA0101.
[38]"Inhibition of homologous recombination by the PCNA-interacting protein PARI."
Moldovan G.L., Dejsuphong D., Petalcorin M.I., Hofmann K., Takeda S., Boulton S.J., D'Andrea A.D.
Mol. Cell 45:75-86(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARPBP, SUMOYLATION.
[39]"Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response."
Centore R.C., Yazinski S.A., Tse A., Zou L.
Mol. Cell 46:625-635(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPRTN.
[40]"ZRANB3 is a structure-specific ATP-dependent endonuclease involved in replication stress response."
Weston R., Peeters H., Ahel D.
Genes Dev. 26:1558-1572(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZRANB3.
[41]"The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress."
Yuan J., Ghosal G., Chen J.
Mol. Cell 47:410-421(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZRANB3.
[42]"Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass."
Povlsen L.K., Beli P., Wagner S.A., Poulsen S.L., Sylvestersen K.B., Poulsen J.W., Nielsen M.L., Bekker-Jensen S., Mailand N., Choudhary C.
Nat. Cell Biol. 14:1089-1098(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KIAA0101.
[43]"Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress."
Ciccia A., Nimonkar A.V., Hu Y., Hajdu I., Achar Y.J., Izhar L., Petit S.A., Adamson B., Yoon J.C., Kowalczykowski S.C., Livingston D.M., Haracska L., Elledge S.J.
Mol. Cell 47:396-409(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZRANB3.
[44]"Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome."
Arboleda V.A., Lee H., Parnaik R., Fleming A., Banerjee A., Ferraz-de-Souza B., Delot E.C., Rodriguez-Fernandez I.A., Braslavsky D., Bergada I., Dell'Angelica E.C., Nelson S.F., Martinez-Agosto J.A., Achermann J.C., Vilain E.
Nat. Genet. 44:788-792(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1C.
[45]"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.
[46]"Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components."
Alabert C., Bukowski-Wills J.C., Lee S.B., Kustatscher G., Nakamura K., de Lima Alves F., Menard P., Mejlvang J., Rappsilber J., Groth A.
Nat. Cell Biol. 16:281-293(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAM111A.
[47]"Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA."
Gulbis J.M., Kelman Z., Hurwitz J., O'Donnell M., Kuriyan J.
Cell 87:297-306(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[48]"Structural basis for recruitment of human flap endonuclease 1 to PCNA."
Sakurai S., Kitano K., Yamaguchi H., Hamada K., Okada K., Fukuda K., Uchida M., Ohtsuka E., Morioka H., Hakoshima T.
EMBO J. 24:683-693(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH FEN1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M15796 mRNA. Translation: AAA35736.1.
J04718 Genomic DNA. Translation: AAA60040.1.
AF527838 Genomic DNA. Translation: AAM78556.1.
AK313286 mRNA. Translation: BAG36094.1.
AL121924 Genomic DNA. Translation: CAC27344.1.
CH471133 Genomic DNA. Translation: EAX10428.1.
CH471133 Genomic DNA. Translation: EAX10429.1.
CH471133 Genomic DNA. Translation: EAX10430.1.
BC000491 mRNA. Translation: AAH00491.1.
BC062439 mRNA. Translation: AAH62439.1.
CCDSCCDS13087.1.
PIRWMHUET. A27445.
RefSeqNP_002583.1. NM_002592.2.
NP_872590.1. NM_182649.1.
UniGeneHs.147433.
Hs.744934.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AXCX-ray2.60A/C/E1-261[»]
1U76X-ray2.60A/C/E1-261[»]
1U7BX-ray1.88A1-261[»]
1UL1X-ray2.90A/B/C1-261[»]
1VYJX-ray2.80A/C/E/G/I/K1-261[»]
1VYMX-ray2.30A/B/C1-261[»]
1W60X-ray3.15A/B1-261[»]
2ZVKX-ray2.70A/B/C1-261[»]
2ZVLX-ray2.50A/B/C/D/E/F1-261[»]
2ZVMX-ray2.30A/B/C1-261[»]
3P87X-ray2.99A/B/C/D/E/F1-261[»]
3TBLX-ray2.90A/B/C1-261[»]
3VKXX-ray2.10A1-261[»]
3WGWX-ray2.80A/B1-261[»]
ProteinModelPortalP12004.
SMRP12004. Positions 1-255.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111142. 216 interactions.
DIPDIP-1098N.
IntActP12004. 50 interactions.
MINTMINT-5000943.
STRING9606.ENSP00000368438.

Chemistry

ChEMBLCHEMBL2346488.

PTM databases

PhosphoSiteP12004.

Polymorphism databases

DMDM129694.

2D gel databases

SWISS-2DPAGEP12004.

Proteomic databases

MaxQBP12004.
PaxDbP12004.
PeptideAtlasP12004.
PRIDEP12004.

Protocols and materials databases

DNASU5111.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379143; ENSP00000368438; ENSG00000132646.
ENST00000379160; ENSP00000368458; ENSG00000132646.
GeneID5111.
KEGGhsa:5111.
UCSCuc002wlp.3. human.

Organism-specific databases

CTD5111.
GeneCardsGC20M005095.
HGNCHGNC:8729. PCNA.
HPACAB000148.
HPA030521.
HPA030522.
HPA030523.
MIM176740. gene.
neXtProtNX_P12004.
PharmGKBPA263.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0592.
HOGENOMHOG000211098.
HOVERGENHBG000947.
InParanoidP12004.
KOK04802.
OMAMKLMNLD.
OrthoDBEOG7JX34W.
PhylomeDBP12004.
TreeFamTF313441.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_216. DNA Repair.
REACT_383. DNA Replication.
SignaLinkP12004.

Gene expression databases

BgeeP12004.
CleanExHS_PCNA.
GenevestigatorP12004.

Family and domain databases

HAMAPMF_00317. DNApol_clamp_arch.
InterProIPR000730. Pr_cel_nuc_antig.
IPR022649. Pr_cel_nuc_antig_C.
IPR022659. Pr_cel_nuc_antig_CS.
IPR022648. Pr_cel_nuc_antig_N.
[Graphical view]
PANTHERPTHR11352. PTHR11352. 1 hit.
PfamPF02747. PCNA_C. 1 hit.
PF00705. PCNA_N. 1 hit.
[Graphical view]
PRINTSPR00339. PCNACYCLIN.
TIGRFAMsTIGR00590. pcna. 1 hit.
PROSITEPS01251. PCNA_1. 1 hit.
PS00293. PCNA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPCNA. human.
EvolutionaryTraceP12004.
GeneWikiProliferating_cell_nuclear_antigen.
GenomeRNAi5111.
NextBio19722.
PROP12004.
SOURCESearch...

Entry information

Entry namePCNA_HUMAN
AccessionPrimary (citable) accession number: P12004
Secondary accession number(s): B2R897, D3DW02
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: July 9, 2014
This is version 169 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM