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PCNA |
Protein FULL name:
Proliferating cell nuclear antigen, Cyclin
Protein SHORT name:
PCNA
PCNA (Homo sapiens) is product of expression of PCNA gene.
PCNA is involved in:
NER in Homo sapiens BER in Homo sapiens
- Strand scission by APEX/PCNA/FEN1/PARP/pol beta/pol delta/lig1 complex in Homo sapiens
- Gap filling and strand displacement with polymerase delta in Homo sapiens
- Strand scission by APEX/PCNA/FEN1/PARP/pol beta/pol epsilon/lig1 complex in Homo sapiens
- Gap filling and strand displacement with polymerase epsilon in Homo sapiens
- Removing overhang by complex with pol delta in Homo sapiens
- Removing overhang by complex with pol epsilon in Homo sapiens
- Ligation of DNA strands by Ligase 1 after processing by polymerase delta in Homo sapiens
- Ligation of DNA strands by Ligase 1 after processing by polymerase epsilon in Homo sapiens
Keywords:
- transcription-coupled repair NER (TCR-NER)
- nucleotide excision repair (NER)
- DNA clamp
- DNA damage tolerance pathway (TLS)
- base excision repair (BER)
- long path BER (LP-BER)
- global genome repair NER (GGR-NER)
FUNCTION: This protein is an 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.
SUBUNIT: Homotrimer (By similarity). Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with EXO1, POLH, POLK, DNMT1, ERCC5, FEN1, CDC6, APEX2 and POLDIP2. Forms a ternary complex with DNTTIP2 and core histone. Interacts with KCTD10 and PPP1R15A (By similarity). 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.
INTERACTION: Q99728:BARD1; NbExp=1; IntAct=EBI-358311, EBI-473181; P38936:CDKN1A; NbExp=1; IntAct=EBI-358311, EBI-375077; P42771:CDKN2A; NbExp=3; IntAct=EBI-358311, EBI-375053; Q13111:CHAF1A; NbExp=1; IntAct=EBI-358311, EBI-1020839; Q05048:CSTF1; NbExp=1; IntAct=EBI-358311, EBI-1789619; P39748:FEN1; NbExp=2; IntAct=EBI-358311, EBI-707816; Q9Z111:Gadd45g (xeno); NbExp=4; IntAct=EBI-358311, EBI-1173616; P17918:Pcna (xeno); NbExp=1; IntAct=EBI-358311, EBI-1173716; P28340:POLD1; NbExp=1; IntAct=EBI-358311, EBI-716569; P49005:POLD2; NbExp=1; IntAct=EBI-358311, EBI-372354; Q15054:POLD3; NbExp=3; IntAct=EBI-358311, EBI-864956; Q9HCU8:POLD4; NbExp=2; IntAct=EBI-358311, EBI-864968; P36873-1:PPP1CC; NbExp=1; IntAct=EBI-358311, EBI-356289;
SUBCELLULAR LOCATION: Nucleus.
PTM: Upon methyl methanesulfonate-induced DNA damage, mono- ubiquitinated by the UBE2B-RAD18 complex on Lys-164. This induces 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, which is required for DNA repair. 'Lys-63' polyubiquitination prevents genomic instability on DNA damage.
PTM: Acetylated in response to UV irradiation. Acetylation disrupts interaction with NUDT15 and promotes degradation.
MISCELLANEOUS: Antibodies against PCNA are present in sera from patients with systemic lupus erythematosus.
SIMILARITY: Belongs to the PCNA family.
WEB RESOURCE: Name=NIEHS-SNPs; [LINK]
WEB RESOURCE: Name=Wikipedia; Note=PCNA entry; [LINK]
| NCBI GenPept GI number(s): |
129694 4505641 |
| Species: | Homo sapiens |
Links to other databases:
| Database | ID | Link |
| Uniprot | P12004 |
P12004 |
| PFAM: |
PF02747 PF00705 |
PF02747 PF00705 |
| InterPro: |
IPR000730 IPR022649 IPR022659 IPR022648 |
IPR000730 IPR022649 IPR022659 IPR022648 |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MFEARLVQGSILKKVLEALKDLINEACWDISSSGVNLQSMDSSHVSLVQL TLRSEGFDTYRCDRNLAMGVNLTSMSKILKCAGNEDIITLRAEDNADTLA LVFEAPNQEKVSDYEMKLMDLDVEQLGIPEQEYSCVVKMPSGEFARICRD LSHIGDAVVISCAKDGVKFSASGELGNGNIKLSQTSNVDKEEEAVTIEMN EPVQLTFALRYLNFFTKATPLSSTVTLSMSADVPLVVEYKIADMGHLKYY LAPKIEDEEGS |
PCNA (Homo sapiens) is able to recognize following damages:
PCNA (Homo sapiens) belongs to following protein families:
References:
| Title | Authors | Journal |
| The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. | Prelich G, Kostura M, Marshak DR, Mathews MB, Stillman B | Nature Jan. 1, 1987 |
| Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins. | Almendral JM, Huebsch D, Blundell PA, Macdonald-Bravo H, Bravo R | Proc Natl Acad Sci U S A March 1, 1987 |
| Structure of the human gene for the proliferating cell nuclear antigen. | Travali S, Ku DH, Rizzo MG, Ottavio L, Baserga R, Calabretta B | J Biol Chem May 5, 1989 |
| Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA. | Gulbis JM, Kelman Z, Hurwitz J, O'Donnell M, Kuriyan J | Cell Oct. 18, 1996 |
| 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 DL, Cornelius HL, MacInnes MA, Park MS | J Biol Chem Sept. 26, 1997 |
| Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. | Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF | Science Sept. 26, 1997 |
| 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 KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A | Mol Cell Biol May 1, 1998 |
| The DNA sequence and comparative analysis of human chromosome 20. | Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J | Nature Jan. 1, 2001 |
| 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 June 1, 2001 |
| Stimulation of DNA synthesis activity of human DNA polymerase kappa by PCNA. | Haracska L, Unk I, Johnson RE, Phillips BB, Hurwitz J, Prakash L, Prakash S | Mol Cell Biol Jan. 1, 2002 |
| 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 EM, Mazloum N, Xie B, Lee MY | J Biol Chem March 21, 2003 |
| 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 June 1, 2003 |
| 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, 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 TO, 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 Feb. 1, 2004 |
| Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. | Kannouche PL, Wing J, Lehmann AR | Mol Cell May 21, 2004 |
| A defined human system that supports bidirectional mismatch-provoked excision. | Dzantiev L, Constantin N, Genschel J, Iyer RR, Burgers PM, Modrich P | Mol Cell July 2, 2004 |
| The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J | Genome Res Oct. 1, 2004 |
| The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. | Poot RA, Bozhenok L, van den Berg DL, Steffensen S, Ferreira F, Grimaldi M, Gilbert N, Ferreira J, Varga-Weisz PD | Nat Cell Biol Dec. 1, 2004 |
| 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 Jan. 23, 2005 |
| 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 EY, Lee MY | J Biol Chem May 26, 2006 |
| 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 EE, Chen J, Harper JW, Walter JC | Mol Cell Sept. 1, 2006 |
| 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 Nov. 28, 2006 |
| Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination. | Motegi A, Sood R, Moinova H, Markowitz SD, Liu PP, Myung K | J Cell Biol Dec. 4, 2006 |
| Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination. | Unk I, Hajdu I, Fatyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L | Proc Natl Acad Sci U S A March 11, 2008 |
| Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. | Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K | Proc Natl Acad Sci U S A Aug. 26, 2008 |
| 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 Sept. 15, 2008 |
| 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 Oct. 24, 2008 |
| PCNA is ubiquitinated by RNF8. | Zhang S, Chea J, Meng X, Zhou Y, Lee EY, Lee MY | Cell Cycle Nov. 1, 2008 |
| Proliferating cell nuclear antigen is protected from degradation by forming a complex with MutT Homolog2. | Yu Y, Cai JP, Tu B, Wu L, Zhao Y, Liu X, Li L, McNutt MA, Feng J, He Q, Yang Y, Wang H, Sekiguchi M, Zhu WG | J Biol Chem July 17, 2009 |
| 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 Aug. 14, 2009 |
| CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. | Terai K, Abbas T, Jazaeri AA, Dutta A | Mol Cell Feb. 15, 2010 |
Last modification of this entry: Oct. 19, 2010.
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