PCNA_BOVIN
ID PCNA_BOVIN Reviewed; 261 AA.
AC Q3ZBW4;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Proliferating cell nuclear antigen;
DE Short=PCNA;
GN Name=PCNA;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Auxiliary protein of DNA polymerase delta and is involved in
CC the control of eukaryotic DNA replication by increasing the
CC polymerase's processibility during elongation of the leading strand.
CC Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-
CC phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease,
CC APEX2 activities. Has to be loaded onto DNA in order to be able to
CC stimulate APEX2. Plays a key role in DNA damage response (DDR) by being
CC conveniently positioned at the replication fork to coordinate DNA
CC replication with DNA repair and DNA damage tolerance pathways. Acts as
CC a loading platform to recruit DDR proteins that allow completion of DNA
CC replication after DNA damage and promote postreplication repair:
CC Monoubiquitinated PCNA leads to recruitment of translesion (TLS)
CC polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is
CC involved in error-free pathway and employs recombination mechanisms to
CC synthesize across the lesion (By similarity).
CC {ECO:0000250|UniProtKB:P12004}.
CC -!- SUBUNIT: Homotrimer. Interacts with p300/EP300; the interaction occurs
CC on chromatin in UV-irradiated damaged cells. Interacts with CREBBP (via
CC transactivation domain and C-terminus); the interaction occurs on
CC chromatin in UV-irradiated damaged cells. Directly interacts with
CC POLD1, POLD3 and POLD4 subunits of the DNA polymerase delta complex,
CC POLD3 being the major interacting partner; the interaction with POLD3
CC is inhibited by CDKN1A/p21(CIP1). Forms a complex with activator 1
CC heteropentamer in the presence of ATP. Interacts with EXO1, POLH, POLK,
CC DNMT1, ERCC5, FEN1, CDC6 and POLDIP2. Interacts with APEX2; this
CC interaction is triggered by reactive oxygen species and increased by
CC misincorporation of uracil in nuclear DNA. Forms a ternary complex with
CC DNTTIP2 and core histone (By similarity). Interacts with KCTD10 and
CC PPP1R15A (By similarity). Interacts with SMARCA5/SNF2H (By similarity).
CC Interacts with BAZ1B/WSTF; the interaction is direct and is required
CC for BAZ1B/WSTF binding to replication foci during S phase (By
CC similarity). Interacts with HLTF and SHPRH. Interacts with NUDT15; this
CC interaction is disrupted in response to UV irradiation and acetylation.
CC Interacts with CDKN1A/p21(CIP1) and CDT1; interacts via their PIP-box
CC which also recruits the DCX(DTL) complex. The interaction with CDKN1A
CC inhibits POLD3 binding. Interacts with DDX11. Interacts with EGFR;
CC positively regulates PCNA. Interacts with PARPBP. Interacts (when
CC ubiquitinated) with SPRTN; leading to enhance RAD18-mediated PCNA
CC ubiquitination. Interacts (when polyubiquitinated) with ZRANB3.
CC Interacts with SMARCAD1. Interacts with CDKN1C. Interacts with PCLAF
CC (via PIP-box). Interacts with RTEL1 (via PIP-box); the interaction is
CC direct and essential for the suppression of telomere fragility.
CC Interacts with FAM111A (via PIP-box); the interaction is direct and
CC required for PCNA loading on chromatin binding. Interacts with LIG1.
CC Interacts with SETMAR. Interacts with ANKRD17. Interacts with
CC FBXO18/FBH1 (via PIP-box); the interaction recruits the DCX(DTL)
CC complex and promotes ubiquitination and degradation of FBXO18/FBH1.
CC Interacts with POLN (By similarity). Interacts with SDE2 (via PIP-box);
CC the interaction is direct and prevents ultraviolet light induced
CC monoubiquitination (By similarity). Component of the replisome complex
CC composed of at least DONSON, MCM2, MCM7, PCNA and TICRR; interaction at
CC least with PCNA occurs during DNA replication (By similarity).
CC Interacts with MAPK15; the interaction is chromatin binding dependent
CC and prevents MDM2-mediated PCNA destruction by inhibiting the
CC association of PCNA with MDM2. Interacts with PARP10 (via PIP-box) (By
CC similarity). Interacts with DDI2 (By similarity). Interacts with HMCES
CC (via PIP-box) (By similarity). Interacts with TRAIP (via PIP-box) (By
CC similarity). Interacts with UHRF2 (By similarity). Interacts with
CC ALKBH2; this interaction is enhanced during the S-phase of the cell
CC cycle. Interacts with ATAD5; the interaction promotes USP1-mediated
CC PCNA deubiquitination (By similarity). {ECO:0000250|UniProtKB:P04961,
CC ECO:0000250|UniProtKB:P12004, ECO:0000250|UniProtKB:P17918}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P12004}.
CC Note=Forms nuclear foci representing sites of ongoing DNA replication
CC and vary in morphology and number during S phase. Together with APEX2,
CC is redistributed in discrete nuclear foci in presence of oxidative DNA
CC damaging agents. Colocalizes with CREBBP, EP300 and POLD1 to sites of
CC DNA damage (By similarity). {ECO:0000250|UniProtKB:P12004}.
CC -!- PTM: Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes
CC chromatin-associated PCNA (By similarity).
CC {ECO:0000250|UniProtKB:P12004}.
CC -!- PTM: Acetylated by CREBBP and p300/EP300; preferentially acetylated by
CC CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon
CC loading on chromatin in response to UV irradiation. Lysine acetylation
CC disrupts association with chromatin, hence promoting PCNA
CC ubiquitination and proteasomal degradation in response to UV damage in
CC a CREBBP- and EP300-dependent manner. Acetylation disrupts interaction
CC with NUDT15 and promotes degradation (By similarity).
CC {ECO:0000250|UniProtKB:P12004}.
CC -!- PTM: Ubiquitinated. Following DNA damage, can be either
CC monoubiquitinated to stimulate direct bypass of DNA lesions by
CC specialized DNA polymerases or polyubiquitinated to promote
CC recombination-dependent DNA synthesis across DNA lesions by template
CC switching mechanisms. Following induction of replication stress,
CC monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to
CC recruit translesion (TLS) polymerases, which are able to synthesize
CC across DNA lesions in a potentially error-prone manner. An error-free
CC pathway also exists and requires non-canonical polyubiquitination on
CC Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2
CC complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH. This
CC error-free pathway, also known as template switching, employs
CC recombination mechanisms to synthesize across the lesion, using as a
CC template the undamaged, newly synthesized strand of the sister
CC chromatid. Monoubiquitination at Lys-164 also takes place in undamaged
CC proliferating cells, and is mediated by the DCX(DTL) complex, leading
CC to enhance PCNA-dependent translesion DNA synthesis. Sumoylated during
CC S phase (By similarity). {ECO:0000250|UniProtKB:P12004}.
CC -!- PTM: Methylated on glutamate residues by ARMT1.
CC {ECO:0000250|UniProtKB:P12004}.
CC -!- SIMILARITY: Belongs to the PCNA family. {ECO:0000305}.
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DR EMBL; BC103068; AAI03069.1; -; mRNA.
DR RefSeq; NP_001029666.1; NM_001034494.1.
DR AlphaFoldDB; Q3ZBW4; -.
DR SMR; Q3ZBW4; -.
DR BioGRID; 172122; 12.
DR STRING; 9913.ENSBTAP00000007967; -.
DR PaxDb; Q3ZBW4; -.
DR PRIDE; Q3ZBW4; -.
DR Ensembl; ENSBTAT00000007967; ENSBTAP00000007967; ENSBTAG00000006065.
DR GeneID; 515499; -.
DR KEGG; bta:515499; -.
DR CTD; 5111; -.
DR VEuPathDB; HostDB:ENSBTAG00000006065; -.
DR VGNC; VGNC:32635; PCNA.
DR eggNOG; KOG1636; Eukaryota.
DR GeneTree; ENSGT00390000004965; -.
DR HOGENOM; CLU_043978_3_0_1; -.
DR InParanoid; Q3ZBW4; -.
DR OMA; EMKLINM; -.
DR OrthoDB; 1012066at2759; -.
DR TreeFam; TF313441; -.
DR Reactome; R-BTA-110312; Translesion synthesis by REV1.
DR Reactome; R-BTA-110320; Translesion Synthesis by POLH.
DR Reactome; R-BTA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-BTA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-BTA-6804114; TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
DR Reactome; R-BTA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000006065; Expressed in pharyngeal tonsil and 108 other tissues.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IEA:Ensembl.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0016604; C:nuclear body; IEA:Ensembl.
DR GO; GO:0005652; C:nuclear lamina; IEA:Ensembl.
DR GO; GO:0043596; C:nuclear replication fork; IEA:Ensembl.
DR GO; GO:0043626; C:PCNA complex; IBA:GO_Central.
DR GO; GO:0070557; C:PCNA-p21 complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0032139; F:dinucleotide insertion or deletion binding; IEA:Ensembl.
DR GO; GO:0070182; F:DNA polymerase binding; IEA:Ensembl.
DR GO; GO:0030337; F:DNA polymerase processivity factor activity; IBA:GO_Central.
DR GO; GO:0035035; F:histone acetyltransferase binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0032405; F:MutLalpha complex binding; IEA:Ensembl.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0000701; F:purine-specific mismatch base pair DNA N-glycosylase activity; IEA:Ensembl.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl.
DR GO; GO:0006287; P:base-excision repair, gap-filling; IEA:Ensembl.
DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0006272; P:leading strand elongation; IBA:GO_Central.
DR GO; GO:0006298; P:mismatch repair; IBA:GO_Central.
DR GO; GO:1902990; P:mitotic telomere maintenance via semi-conservative replication; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0032077; P:positive regulation of deoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IEA:Ensembl.
DR GO; GO:0045740; P:positive regulation of DNA replication; IEA:Ensembl.
DR GO; GO:1900264; P:positive regulation of DNA-directed DNA polymerase activity; IEA:Ensembl.
DR GO; GO:0031297; P:replication fork processing; IEA:Ensembl.
DR GO; GO:0019985; P:translesion synthesis; ISS:UniProtKB.
DR HAMAP; MF_00317; DNApol_clamp_arch; 1.
DR InterPro; IPR000730; Pr_cel_nuc_antig.
DR InterPro; IPR022649; Pr_cel_nuc_antig_C.
DR InterPro; IPR022659; Pr_cel_nuc_antig_CS.
DR InterPro; IPR022648; Pr_cel_nuc_antig_N.
DR Pfam; PF02747; PCNA_C; 1.
DR Pfam; PF00705; PCNA_N; 1.
DR PRINTS; PR00339; PCNACYCLIN.
DR TIGRFAMs; TIGR00590; pcna; 1.
DR PROSITE; PS01251; PCNA_1; 1.
DR PROSITE; PS00293; PCNA_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; DNA damage; DNA repair; DNA replication; DNA-binding;
KW Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..261
FT /note="Proliferating cell nuclear antigen"
FT /id="PRO_0000284917"
FT DNA_BIND 61..80
FT /evidence="ECO:0000255"
FT MOD_RES 14
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12004"
FT MOD_RES 77
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12004"
FT MOD_RES 80
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12004"
FT MOD_RES 211
FT /note="Phosphotyrosine; by EGFR"
FT /evidence="ECO:0000250|UniProtKB:P12004"
FT MOD_RES 248
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12004"
FT CROSSLNK 164
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P12004"
FT CROSSLNK 164
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P12004"
FT CROSSLNK 254
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P12004"
SQ SEQUENCE 261 AA; 28749 MW; D9D3E20EC7A8F9FD CRC64;
MFEARLVQGS ILKKVLEALK DLINEACWDI SSSGVNLQSM DSSHVSLVQL TLRSEGFDTY
RCDRNLAMGV NLTSMSKILK CAGNEDIITL RAEDNADTLA LVFEAPNQEK VSDYEMKLMD
LDVEQLGIPE QEYSCVVKMP SGEFARICRD LSHIGDAVVI SCAKDGVKFS ASGELGNGNI
KLSQTSNVDK EEEAVAIEMN EPVQLTFALR YLNFFTKATP LSPTVTLSMS ADVPLVVEYK
IADMGHLKYY LAPKIEDEEG S
