Tchem PCNA Proliferating cell nuclear antigen

Protein Summary

Description

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. 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. The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P12004
• B2R897
• D3DW02
• PCNA

Gene Name

• PCNA

Ensembl ID

• ENST00000379143
• ENSP00000368438
• ENSG00000132646
• ENST00000379160
• ENSP00000368458

Symbol

• ATLD2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
chemical	1
co-expressed gene	1
hub protein	1
molecular function	0.94
transcription factor binding site profile	0.94

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 20.69   (req: < 5)

Gene RIFs: 328   (req: <= 3)

Antibodies: 2300   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 20.69   (req: >= 5)

Gene RIFs: 328   (req: > 3)

Antibodies: 2300   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 44

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

Show Full Sequence

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Active Ligands (2)

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1 – 2 of 2

CHEMBL2348305

PCNATchem

pIC50 : 6

CHEMBL2348291

PCNATchem

pIC50 : 6

Protein-Protein Interactions (551)

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1 – 10 of 551

• See Interactions on String-DB

FEN1

Tchem

Family:  Enzyme

Novelty:  0.00082515

p_int:  0.999924849

p_ni:  0.000075151

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

PCLAF

Tbio

Novelty:  0.00328133

p_int:  0.999594644

p_ni:  0.000405356

Score:  0.997

Data Source:  BioPlex,STRINGDB

CCNE1

Tchem

Novelty:  0.00237201

p_int:  0.998873777

p_ni:  0.000097202

p_wrong:  0.001029021

Score:  0.991

Data Source:  BioPlex,STRINGDB

CCNA2

Tchem

Novelty:  0.00049887

p_int:  0.996352886

p_ni:  0.003647114

Score:  0.921

Data Source:  BioPlex,STRINGDB

CDK2

Tchem

Family:  Kinase

Novelty:  0.00032118

p_int:  0.995200662

p_ni:  0.004799338

Score:  0.994

Data Source:  BioPlex,STRINGDB

FANCM

Tbio

Novelty:  0.01122278

p_int:  0.993858826

p_ni:  0.006141174

Score:  0.934

Data Source:  BioPlex,STRINGDB

CDKN1A

Tchem

Family:  Enzyme

Novelty:  0.00033009

p_int:  0.989609886

p_ni:  0.010390114

p_wrong:  1e-9

Score:  0.999

Data Source:  BioPlex,STRINGDB

CCNB1

Tchem

Novelty:  0.0005503

p_int:  0.90507448

p_ni:  0.094925439

p_wrong:  8.1e-8

Score:  0.937

Data Source:  BioPlex,STRINGDB

CCNE2

Tbio

Novelty:  0.00795182

p_int:  0.889944577

p_ni:  0.000123419

p_wrong:  0.109932004

Score:  0.931

Data Source:  BioPlex,STRINGDB

RFC4

Tbio

Novelty:  0.03232586

Score:  0.999

Data Source:  STRINGDB

Pathways (108)

Reactome (63)

KEGG (7)

PathwayCommons (4)

WikiPathways (34)

Base Excision Repair (R-HSA-73884)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Base Excision Repair	72 targets	R-HSA-73884
Reactome	Cell Cycle	597 targets	R-HSA-1640170
Reactome	Cell Cycle, Mitotic	495 targets	R-HSA-69278
Reactome	Chromosome Maintenance	88 targets	R-HSA-73886
Reactome	DNA Damage Bypass	47 targets	R-HSA-73893

Name	Explore in Pharos	Explore in Source
Base Excision Repair	72 targets	R-HSA-73884
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle, Mitotic	495 targets	R-HSA-69278
Chromosome Maintenance	88 targets	R-HSA-73886
DNA Damage Bypass	47 targets	R-HSA-73893

Gene Ontology Terms (57)

Functions (12)

Components (13)

Processes (32)

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GO Term	Evidence	Assigned by
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
damaged DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
dinucleotide insertion or deletion binding	Inferred from Direct Assay (IDA)	BHF-UCL
MutLalpha complex binding	Inferred from Direct Assay (IDA)	HGNC
purine-specific mismatch base pair DNA N-glycosylase activity	Inferred from Direct Assay (IDA)	BHF-UCL
DNA polymerase binding	Inferred from Physical Interaction (IPI)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	BHF-UCL
histone acetyltransferase binding	Inferred from Physical Interaction (IPI)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
receptor tyrosine kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB

GWAS Traits (1)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
viral load	EFO_0010125	1	1	1		66.8

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
viral load	EFO_0010125	1		66.8

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Complete proteome
Deafness
Direct protein sequencing
Disease mutation
DNA damage
DNA repair
DNA replication
DNA-binding

GWAS Trait Find Similar Targets

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viral load

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
immune system phenotype
mortality/aging
reproductive system phenotype

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	proliferating cell nuclear antigen	VGNC:6229	458081
Macaque	proliferating cell nuclear antigen		718006
Mouse	proliferating cell nuclear antigen	MGI:97503	18538
Mouse	proliferating cell nuclear antigen pseudogene 2	MGI:97505	18540
Rat	proliferating cell nuclear antigen	RGD:3269	25737

Species	Name	OMA	EggNOG	Inparanoid
Chimp	proliferating cell nuclear antigen
Macaque	proliferating cell nuclear antigen
Mouse	proliferating cell nuclear antigen
Mouse	proliferating cell nuclear antigen pseudogene 2
Rat	proliferating cell nuclear antigen

Publication Statistics

PubMed Score 20.69

PubMed score by year

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PubTator Score 4943.27

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