Protein: Proliferating cell nuclear antigen (PCNA) (Cyclin) (P12004)
Organism: Homo sapiens (Human)
Function: Auxiliary protein of DNA polymerase delta and epsilon, 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.
Subcellular location: Nucleus {ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:24115439, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:38459011}. Note=Colocalizes with CREBBP, EP300 and POLD1 to sites of DNA damage (PubMed:24939902). Forms nuclear foci representing sites of ongoing DNA replication and vary in morphology and number during S phase (PubMed:15543136). Co-localizes with SMARCA5/SNF2H and BAZ1B/WSTF at replication foci during S phase (PubMed:15543136). Together with APEX2, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents. {ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:24939902}.
Sequence: MFEARLVQGSILKKVLEALKDLINEACWDISSSGVNLQSMDSSHVSLVQLTLRSEGFDTYRCDRNLAMGVNLTSMSKILKCAGNEDIITLRAEDNADTLALVFEAPNQEKVSDYEMKLMDLDVEQLGIPEQEYSCVVKMPSGEFARICRDLSHIGDAVVISCAKDGVKFSASGELGNGNIKLSQTSNVDKEEEAVTIEMNEPVQLTFALRYLNFFTKATPLSSTVTLSMSADVPLVVEYKIADMGHLKYYLAPKIEDEEGS
InterPro domains: - IPR046938: DNA clamp superfamily (homologous_superfamily) [1-255]
- IPR000730: Proliferating cell nuclear antigen, PCNA (family) [1-259]
- IPR022648: Proliferating cell nuclear antigen, PCNA, N-terminal (domain) [1-124]
- IPR022649: Proliferating cell nuclear antigen, PCNA, C-terminal (domain) [127-254]
- IPR022659: Proliferating cell nuclear antigen, PCNA, conserved site (conserved_site) [34-79]
Interaction partners: - DNA polymerase eta
- DNA polymerase delta catalytic subunit
- Flap endonuclease 1
- Cyclin-dependent kinase inhibitor 1
- Replication factor C subunit 3
- Replication factor C subunit 2
- Replication factor C subunit 4
- DNA ligase 1
- Replication factor C subunit 5
- Replication factor C subunit 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0009628 (response to abiotic stimulus), GO:0009058 (biosynthetic process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0022402 (cell cycle process), GO:0006807 (nitrogen compound metabolic process), GO:0007049 (cell cycle), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0044238 (primary metabolic process), GO:0050790 (regulation of catalytic activity), GO:0044093 (positive regulation of molecular function), GO:1901576 (organic substance biosynthetic process), GO:1903047 (mitotic cell cycle process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0009314 (response to radiation), GO:0044786 (cell cycle DNA replication), GO:0060255 (regulation of macromolecule metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:0104004 (cellular response to environmental stimulus), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0033554 (cellular response to stress), GO:0071214 (cellular response to abiotic stimulus), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0016043 (cellular component organization), GO:0080090 (regulation of primary metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0000278 (mitotic cell cycle), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0071478 (cellular response to radiation), GO:0009059 (macromolecule biosynthetic process), GO:0009416 (response to light stimulus), GO:1901362 (organic cyclic compound biosynthetic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051052 (regulation of DNA metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0051054 (positive regulation of DNA metabolic process), GO:0019438 (aromatic compound biosynthetic process), GO:0033260 (nuclear DNA replication), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0018130 (heterocycle biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0006259 (DNA metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0051338 (regulation of transferase activity), GO:0043085 (positive regulation of catalytic activity), GO:0006996 (organelle organization), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0071897 (DNA biosynthetic process), GO:0051347 (positive regulation of transferase activity), GO:0006281 (DNA repair), GO:0051276 (chromosome organization), GO:2000573 (positive regulation of DNA biosynthetic process), GO:0022616 (DNA strand elongation), GO:0006260 (DNA replication), GO:0006275 (regulation of DNA replication), GO:2000278 (regulation of DNA biosynthetic process), GO:0009411 (response to UV), GO:0006261 (DNA-templated DNA replication), GO:0006271 (DNA strand elongation involved in DNA replication), GO:0006301 (postreplication repair), GO:0090329 (regulation of DNA-templated DNA replication), GO:0000731 (DNA synthesis involved in DNA repair), GO:0034644 (cellular response to UV), GO:0019985 (translesion synthesis), GO:0042276 (error-prone translesion synthesis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)