UniProt Accession

 PCNA_HUMAN; P12004; B2R897; D3DW02 

Genbank Protein ID

 M15796; J04718; AF527838; AK313286; AL121924; CH471133; CH471133; CH471133; BC000491; BC062439 

Genbank Nucleotide ID

 AAA35736.1; AAA60040.1; AAM78556.1; BAG36094.1; CAC27344.1; EAX10428.1; EAX10429.1; EAX10430.1; AAH00491.1; AAH62439.1 

Protein Name

 Proliferating cell nuclear antigen 

Protein Synonyms/Alias

 PCNA; Cyclin 

Gene Name

 PCNA 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
13	LVQGSILKKVLEALK	acetylation	[1, 2]
13	LVQGSILKKVLEALK	ubiquitination	[2, 3, 4, 5, 6, 7]
14	VQGSILKKVLEALKD	ubiquitination	[3, 5, 7, 8]
77	VNLTSMSKILKCAGN	acetylation	[9]
77	VNLTSMSKILKCAGN	ubiquitination	[2, 3, 4, 5, 7, 8, 10]
80	TSMSKILKCAGNEDI	acetylation	[1, 2, 9]
80	TSMSKILKCAGNEDI	ubiquitination	[2, 3, 4, 5, 7, 8, 10, 11, 12, 13]
110	FEAPNQEKVSDYEMK	ubiquitination	[2, 4, 5, 6, 10]
117	KVSDYEMKLMDLDVE	ubiquitination	[2, 5, 10, 13]
138	QEYSCVVKMPSGEFA	ubiquitination	[2, 5, 10, 13]
164	AVVISCAKDGVKFSA	acetylation	[2]
164	AVVISCAKDGVKFSA	sumoylation	[14, 15, 16]
164	AVVISCAKDGVKFSA	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 17, 18, 19]
168	SCAKDGVKFSASGEL	ubiquitination	[2, 5]
181	ELGNGNIKLSQTSNV	ubiquitination	[3, 7]
217	RYLNFFTKATPLSST	ubiquitination	[6]
248	IADMGHLKYYLAPKI	acetylation	[2, 9, 20]
248	IADMGHLKYYLAPKI	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 10, 11, 13, 18]
254	LKYYLAPKIEDEEGS	ubiquitination	[2, 4, 5, 6, 10, 12, 13, 17]

Reference

 [1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [9] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [10] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [11] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [12] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [13] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [14] Translesion synthesis in mammalian cells.
 Lehmann AR.
 Exp Cell Res. 2006 Aug 15;312(14):2673-6. [PMID: 16854411]
 [15] Translesion synthesis: Y-family polymerases and the polymerase switch.
 Lehmann AR, Niimi A, Ogi T, Brown S, Sabbioneda S, Wing JF, Kannouche PL, Green CM.
 DNA Repair (Amst). 2007 Jul 1;6(7):891-9. [PMID: 17363342]
 [16] Regulation of double-stranded DNA gap repair by the RAD6 pathway.
 Moertl S, Karras GI, Wismüller T, Ahne F, Eckardt-Schupp F.
 DNA Repair (Amst). 2008 Nov 1;7(11):1893-906. [PMID: 18722556]
 [17] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [18] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [19] Proteomic snapshot of the EGF-induced ubiquitin network.
 Argenzio E, Bange T, Oldrini B, Bianchi F, Peesari R, Mari S, Di Fiore PP, Mann M, Polo S.
 Mol Syst Biol. 2011 Jan 18;7:462. [PMID: 21245847]
 [20] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773] 

Functional Description

 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. 

Sequence Annotation

 DNA_BIND 61 80 Potential.
 REGION 7 100 Interaction with NUDT15.
 MOD_RES 14 14 N6-acetyllysine.
 MOD_RES 77 77 N6-acetyllysine.
 MOD_RES 80 80 N6-acetyllysine.
 MOD_RES 211 211 Phosphotyrosine; by EGFR.
 MOD_RES 248 248 N6-acetyllysine.
 CROSSLNK 164 164 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Complete proteome; Direct protein sequencing; DNA damage; DNA repair; DNA replication; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 261 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:HPA.
 GO:0005663; C:DNA replication factor C complex; TAS:UniProtKB.
 GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
 GO:0043596; C:nuclear replication fork; IDA:BHF-UCL.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0043626; C:PCNA complex; IEA:InterPro.
 GO:0070557; C:PCNA-p21 complex; IDA:UniProtKB.
 GO:0032139; F:dinucleotide insertion or deletion binding; IDA:BHF-UCL.
 GO:0030337; F:DNA polymerase processivity factor activity; IEA:InterPro.
 GO:0032405; F:MutLalpha complex binding; IDA:HGNC.
 GO:0000701; F:purine-specific mismatch base pair DNA N-glycosylase activity; IDA:BHF-UCL.
 GO:0006284; P:base-excision repair; TAS:Reactome.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0006271; P:DNA strand elongation involved in DNA replication; TAS:Reactome.
 GO:0007507; P:heart development; IEA:Compara.
 GO:0006298; P:mismatch repair; IDA:BHF-UCL.
 GO:0006297; P:nucleotide-excision repair, DNA gap filling; TAS:Reactome.
 GO:0048015; P:phosphatidylinositol-mediated signaling; NAS:UniProtKB.
 GO:0032077; P:positive regulation of deoxyribonuclease activity; IDA:UniProtKB.
 GO:0006275; P:regulation of DNA replication; IEA:InterPro.
 GO:0000083; P:regulation of transcription involved in G1/S phase of mitotic cell cycle; TAS:Reactome.
 GO:0046686; P:response to cadmium ion; IEA:Compara.
 GO:0033993; P:response to lipid; IEA:Compara.
 GO:0000722; P:telomere maintenance via recombination; TAS:Reactome.
 GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome.
 GO:0006283; P:transcription-coupled nucleotide-excision repair; TAS:Reactome.
 GO:0019985; P:translesion synthesis; IDA:UniProtKB. 

Interpro

 IPR000730; Pr_cel_nuc_antig.
 IPR022649; Pr_cel_nuc_antig_C.
 IPR022659; Pr_cel_nuc_antig_CS.
 IPR022648; Pr_cel_nuc_antig_N. 

Pfam

 PF02747; PCNA_C
 PF00705; PCNA_N 

SMART

  

PROSITE

 PS01251; PCNA_1
 PS00293; PCNA_2 

PRINTS

 PR00339; PCNACYCLIN.