Proliferating cell nuclear antigen - Homo sapiens (Human)

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Names and origin

Protein names

Recommended name:
    Proliferating cell nuclear antigen
      Short name=PCNA
Alternative name(s):
    Cyclin

Gene names

Name:

PCNA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	261 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

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 structure	Homotrimer. Interacts with KCTD10. Interacts with PPP1R15A By similarity. Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with POLH, POLK, DNMT1, ERCC5/XPG, FEN1, CDC6, APEX2 and POLDIP2. Interacts with EXO1 and SHPRH. Forms a ternary complex with DNTTIP2 and core histone. Interacts with POLD1, POLD3 and POLD4.
Subcellular location	Nucleus.
Post-translational modification	Upon methyl methanesulfonate-induced DNA damage, mono-ubiquitinated by the UBE2B-RAD18 complex on Lys-164. This induces non-canonical poly-ubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligase SHPRH, whih is required for DNA repair.
Involvement in disease	Antibodies are present in sera from patients with systemic lupus erythematosus.
Sequence similarities	Belongs to the PCNA family.

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Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Disease	Systemic lupus erythematosus
Ligand	DNA-binding
PTM	Ubl conjugation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell proliferation Ref.2 Traceable author statement. Source: ProtInc nucleotide-excision repair, DNA gap filling Inferred from Experiment. Source: Reactome phosphoinositide-mediated signaling Non-traceable author statement. Source: UniProtKB regulation of DNA replication Inferred from electronic annotation. Source: InterPro
Cellular component	DNA replication factor C complex Ref.2 Traceable author statement. Source: UniProtKB PCNA complex Inferred from electronic annotation. Source: InterPro nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro DNA polymerase processivity factor activity Inferred from electronic annotation. Source: InterPro MutLalpha complex binding Inferred from direct assay. Source: HGNC
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
BARD1	Q99728	1	EBI-358311,EBI-473181
CDKN2A	P42771	3	EBI-358311,EBI-375053
CHAF1A	Q13111	1	EBI-358311,EBI-1020839
CSTF1	Q05048	1	EBI-358311,EBI-1789619
FEN1	P39748	2	EBI-358311,EBI-707816
Gadd45g	Q9Z111	4	EBI-358311,EBI-1173616	From a different organism.
PPP1CC	P36873-1	1	EBI-358311,EBI-356289

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 261

261

Proliferating cell nuclear antigen

PRO_0000149158

Regions

DNA binding

61 – 80

20

Potential

Amino acid modifications

Cross-link

164

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Experimental info

Mutagenesis

164

1

K → R: Abolishes ubiquitination. No effect on interaction with SHPRH

Secondary structure

1

.

261

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P12004-1 [UniParc].

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

261

28,769

        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

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References

	« Hide 'large scale' referencesShow '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: 2882507] [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: 2565339] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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. Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow and Lung.
[6]	"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: 2882422] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-26.
[7]	"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: 9305916] [Abstract] Cited for: INTERACTION WITH ERCC5/XPG.
[8]	"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: 9302295] [Abstract] Cited for: INTERACTION WITH DNMT1.
[9]	"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: 9566895] [Abstract] Cited for: INTERACTION WITH CDC6.
[10]	"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: 11376153] [Abstract] Cited for: INTERACTION WITH APEX2.
[11]	"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: 11784855] [Abstract] Cited for: INTERACTION WITH POLK.
[12]	"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: 12786946] [Abstract] Cited for: INTERACTION WITH DNTTIP2.
[13]	"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: 12522211] [Abstract] Cited for: INTERACTION WITH POLDIP2. Tissue: Placenta.
[14]	"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: 15225546] [Abstract] Cited for: INTERACTION WITH EXO1.
[15]	"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: 15149598] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH POLH.
[16]	"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: 16510448] [Abstract] Cited for: INTERACTION WITH POLD1; POLD3 AND POLD4.
[17]	"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: 17130289] [Abstract] Cited for: INTERACTION WITH SHPRH, UBIQUITINATION AT LYS-164, MUTAGENESIS OF LYS-164.
[18]	"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: 17108083] [Abstract] Cited for: UBIQUITINATION AT LYS-164, MUTAGENESIS OF LYS-164.
[19]	"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: 8861913] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[20]	"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: 15616578] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH PCNA.
+	Additional computationally mapped references.

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Web resources

Wikipedia

PCNA entry

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Cross-references

Sequence databases

M15796 mRNA. Translation: AAA35736.1.
J04718 Genomic DNA. Translation: AAA60040.1.
AF527838 Genomic DNA. Translation: AAM78556.1.
AL121924 Genomic DNA. Translation: CAC27344.1.
BC000491 mRNA. Translation: AAH00491.1.
BC062439 mRNA. Translation: AAH62439.1.

PIR

WMHUET. A27445.

RefSeq

NP_002583.1.
NP_872590.1.

UniGene

Hs.147433

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AXC	X-ray	2.60	A/C/E	1-261	[»]
1U76	X-ray	2.60	A/C/E	1-261	[»]
1U7B	X-ray	1.88	A	1-261	[»]
1UL1	X-ray	2.90	A/B/C	1-261	[»]
1VYJ	X-ray	2.80	A/C/E/G/I/K	1-261	[»]
1VYM	X-ray	2.30	A/B/C	1-261	[»]
1W60	X-ray	3.15	A/B	1-261	[»]