PCNA
entrez
5111
canonical
uniprot
P12004
canonical
ensembl
ENSG00000132646
resolver
ensp
ENSP00000368438
resolver
ensp
ENSP00000368458
resolver
ensp
ENSP00000545716
resolver
ensp
ENSP00000638105
resolver
enst
ENST00000379143
resolver
enst
ENST00000379160
resolver
enst
ENST00000875657
resolver
enst
ENST00000968046
resolver
genesymbol
PCNA
resolver
hgnc
HGNC:8729
resolver
uniprot
B2R897
resolver
uniprot
D3DW02
resolver
uniprot_entry
PCNA_HUMAN
resolver
uniprot_sec
B2R897
resolver
uniprot_sec
D3DW02
resolver
amino_acid_sequence
MFEARLVQGSILKKVLEALKDLINEACWDISSSGVNLQSMDSSHVSLVQLTLRSEGFDTYRCDRNLAMGVNLTSMSKILKCAGNEDIITLRAEDNADTLALVFEAPNQEKVSDYEMKLMDLDVEQLGIPEQEYSCVVKMPSGEFARICRDLSHIGDAVVISCAKDGVKFSASGELGNGNIKLSQTSNVDKEEEAVTIEMNEPVQLTFALRYLNFFTKATPLSSTVTLSMSADVPLVVEYKIADMGHLKYYLAPKIEDEEGS
uniprot
proteins
disease_involvement
DISEASE: Ataxia-telangiectasia-like disorder 2 (ATLD2) [MIM:615919]: A neurodegenerative disorder due to defects in DNA excision repair. ATLD2 is characterized by developmental delay, ataxia, sensorineural hearing loss, short stature, cutaneous and ocular telangiectasia, and photosensitivity. {ECO:0000269|PubMed:24911150}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Confers DNA tethering and processivity to DNA polymerases and other proteins (PubMed:24695737, PubMed:24939902, PubMed:35585232). Auxiliary protein of DNA polymerase delta and epsilon, is involved in the control of DNA replication by increasing the polymerases' processivity during elongation of the leading strand (PubMed:35585232). 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 (PubMed:24939902). 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 (PubMed:24695737). {ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19443450, ECO:0000269|PubMed:24695737, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:38459011}.
uniprot
proteins
mass_dalton
28769
uniprot
proteins
mutagenesis
MUTAGEN 13; /note="K->R: Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-14; R-20; R-77 and R-80."; /evidence="ECO:0000269|PubMed:24939902"; MUTAGEN 14; /note="K->R: Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-20; R-77 and R-80."; /evidence="ECO:0000269|PubMed:24939902"; MUTAGEN 20; /note="K->R: Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-14; R-77 and R-80."; /evidence="ECO:0000269|PubMed:24939902"; MUTAGEN 40; /note="M->A: Complete loss of interaction with UHRF2."; /evidence="ECO:0000269|PubMed:11595739"; MUTAGEN 43..45; /note="SHV->AAA: No effect on POLD3-binding. Impairs binding to ALKBH2."; /evidence="ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:26408825"; MUTAGEN 77; /note="K->A: Inhibits recruitment to DNA damage sites, but nuclear localization is similar as the wild-type; in association with A-80."; /evidence="ECO:0000269|PubMed:24939902"; MUTAGEN 77; /note="K->R: Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-14; R-20 and R-80."; /evidence="ECO:0000269|PubMed:24939902"; MUTAGEN 80; /note="K->A: Inhibits recruitment to DNA damage sites, but nuclear localization is similar as the wild-type; in association with A-77."; /evidence="ECO:0000269|PubMed:24939902"; MUTAGEN 80; /note="K->R: Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-14; R-20 and R-77."; /evidence="ECO:0000269|PubMed:24939902"; MUTAGEN 125..128; /note="QLGI->AAAA: Strong decrease in POLD3-binding. Impairs binding to ALKBH2."; /evidence="ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:26408825"; MUTAGEN 128; /note="I->A: Complete loss of interaction with UHRF2."; /evidence="ECO:0000269|PubMed:11595739"; MUTAGEN 164; /note="K->R: Abolishes ubiquitination. No effect on interaction with SHPRH."; /evidence="ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:20129063"; MUTAGEN 188..190; /note="VDK->AAA: No effect on POLD3-binding. No effect on ALKBH2-binding."; /evidence="ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:26408825"; MUTAGEN 211; /note="Y->F: Alters chromatin-associated PCNA stability and its function in DNA replication and repair."; /evidence="ECO:0000269|PubMed:17115032"; MUTAGEN 250; /note="Y->A: Complete loss of interaction with UHRF2."; /evidence="ECO:0000269|PubMed:11595739"; MUTAGEN 251..254; /note="LAPK->AAAA: Decrease in POLD3-binding."; /evidence="ECO:0000269|PubMed:11595739"; MUTAGEN 252; /note="A->G: Complete loss of interaction with UHRF2."; /evidence="ECO:0000269|PubMed:11595739
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA. {ECO:0000269|PubMed:17115032}.; PTM: Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation (PubMed:19419956, PubMed:24939902). Lysine acetylation disrupts association with chromatin, hence promoting PCNA ubiquitination and proteasomal degradation in response to UV damage in a CREBBP- and EP300-dependent manner (PubMed:24939902). Acetylation disrupts interaction with NUDT15 and promotes degradation (PubMed:19419956). {ECO:0000269|PubMed:24939902}.; PTM: Ubiquitinated (PubMed:20227374, PubMed:24939902). 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. {ECO:0000269|PubMed:15149598, ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22153967, ECO:0000269|PubMed:24939902}.; PTM: Methylated on glutamate residues by DCPH1/C6orf211. {ECO:0000269|PubMed:25732820}.
uniprot
proteins
protein_family
PCNA family
uniprot
proteins
pubmed
11376153
uniprot
proteins
pubmed
11595739
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
11784855
uniprot
proteins
pubmed
12522211
uniprot
proteins
pubmed
12786946
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15149598
uniprot
proteins
pubmed
15225546
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15543136
uniprot
proteins
pubmed
15616578
uniprot
proteins
pubmed
16510448
uniprot
proteins
pubmed
16949367
uniprot
proteins
pubmed
17108083
uniprot
proteins
pubmed
17115032
uniprot
proteins
pubmed
17130289
uniprot
proteins
pubmed
18316726
uniprot
proteins
pubmed
18499658
uniprot
proteins
pubmed
18703516
uniprot
proteins
pubmed
18719106
uniprot
proteins
pubmed
18794347
uniprot
proteins
pubmed
18948756
uniprot
proteins
pubmed
19336415
uniprot
proteins
pubmed
19419956
uniprot
proteins
pubmed
19443450
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19995904
uniprot
proteins
pubmed
20129063
uniprot
proteins
pubmed
20147293
uniprot
proteins
pubmed
20227374
uniprot
proteins
pubmed
20457750
uniprot
proteins
pubmed
20733054
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21549307
uniprot
proteins
pubmed
21628590
uniprot
proteins
pubmed
22148433
uniprot
proteins
pubmed
22153967
uniprot
proteins
pubmed
22521144
uniprot
proteins
pubmed
22634751
uniprot
proteins
pubmed
22681887
uniprot
proteins
pubmed
22704558
uniprot
proteins
pubmed
22705370
uniprot
proteins
pubmed
22759634
uniprot
proteins
pubmed
23000965
uniprot
proteins
pubmed
23677613
uniprot
proteins
pubmed
23711367
uniprot
proteins
pubmed
24115439
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24561620
uniprot
proteins
pubmed
24695737
uniprot
proteins
pubmed
24911150
uniprot
proteins
pubmed
24939902
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
2565339
uniprot
proteins
pubmed
25732820
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26223641
uniprot
proteins
pubmed
26408825
uniprot
proteins
pubmed
26711499
uniprot
proteins
pubmed
26760506
uniprot
proteins
pubmed
27084448
uniprot
proteins
pubmed
27462463
uniprot
proteins
pubmed
27906959
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28191891
uniprot
proteins
pubmed
28621305
uniprot
proteins
pubmed
2882422
uniprot
proteins
pubmed
2882507
uniprot
proteins
pubmed
28951215
uniprot
proteins
pubmed
29290612
uniprot
proteins
pubmed
30554877
uniprot
proteins
pubmed
35585232
uniprot
proteins
pubmed
35849344
uniprot
proteins
pubmed
37014751
uniprot
proteins
pubmed
37218877
uniprot
proteins
pubmed
38459011
uniprot
proteins
pubmed
8861913
uniprot
proteins
pubmed
9302295
uniprot
proteins
pubmed
9305916
uniprot
proteins
pubmed
9566895
uniprot
proteins
sequence_length
261
uniprot
proteins
subcellular_location
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}.
uniprot
proteins