Tchem PRKDC DNA-dependent protein kinase catalytic subunit

Protein Summary

Description

Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010]

Uniprot Accession IDs

• P78527
• P78528
• Q13327
• Q13337
• Q14175
• Q59H99
• Q7Z611
• Q96SE6
• Q9UME3
• DNA-PK catalytic subunit

Gene Name

• PRKDC

Ensembl ID

• ENST00000314191
• ENSP00000313420
• ENSG00000253729
• ENST00000338368
• ENSP00000345182

Symbol

• HYRC
• HYRC1
• HYRC
• p350
• DNAPK
• DNPK1
• HYRC1
• IMD26
• XRCC7
• DNAPKc
• DNA-PKC
• DNA-PKcs

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
interacting protein	1
protein domain	0.99
molecular function	0.98

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: 985.7   (req: < 5)

Gene RIFs: 265   (req: <= 3)

Antibodies: 1451   (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: 985.7   (req: >= 5)

Gene RIFs: 265   (req: > 3)

Antibodies: 1451   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 53

Tchem

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

Active Ligands: 169

Tclin

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

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Active Ligands (169)

Explore Active Ligands

1 – 10 of 169

PP121

PRKDCTchem Kinase

pIC50 : 7.22

torin 2

PRKDCTchem Kinase

pIC50 : 9.3

CHEMBL1615189

PRKDCTchem Kinase

pKi : 8.52

wortmannin

PRKDCTchem Kinase

pKi : 6.92

PIK-75

PRKDCTchem Kinase

pIC50 : 8.7

PI-103

PRKDCTchem Kinase

pIC50 : 8.7

CHEMBL1241578

PRKDCTchem Kinase

pIC50 : 7.77

CHEMBL1738719

PRKDCTchem Kinase

pIC50 : 8.64

CHEMBL1914743

PRKDCTchem Kinase

pIC50 : 8.47

CHEMBL1241676

PRKDCTchem Kinase

pIC50 : 7.89

Protein-Protein Interactions (369)

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• See Interactions on String-DB

EPHA1

Tchem

Family:  Kinase

Novelty:  0.00136672

p_int:  0.970813602

p_ni:  0.029186398

Score:  0.236

Data Source:  BioPlex,STRINGDB

PPP6R2

Tbio

Family:  Enzyme

Novelty:  0.12886225

p_int:  0.941070431

p_ni:  0.058929569

Score:  0.566

Data Source:  BioPlex,STRINGDB

LPAR4

Tchem

Family:  GPCR

Novelty:  0.02200758

p_int:  0.879562939

p_ni:  0.120437061

Score:  0.19

Data Source:  BioPlex,STRINGDB

DCLRE1C

Tbio

Novelty:  0.01064408

p_int:  0.783080242

p_ni:  0.216919758

Score:  0.978

Data Source:  BioPlex,Reactome,STRINGDB

XRCC4

Tbio

Novelty:  0.00305644

Score:  0.999

Data Source:  Reactome,STRINGDB

XRCC6

Tbio

Novelty:  0.00127955

Score:  0.999

Data Source:  Reactome,STRINGDB

XRCC5

Tbio

Novelty:  0.00150735

Score:  0.999

Data Source:  Reactome,STRINGDB

H2AFX

Tbio

Novelty:  0.00048694

Score:  0.993

Data Source:  STRINGDB

NHEJ1

Tbio

Novelty:  0.00773499

Score:  0.992

Data Source:  Reactome,STRINGDB

LIG4

Tbio

Family:  Enzyme

Novelty:  0.00412993

Score:  0.992

Data Source:  Reactome,STRINGDB

Pathways (29)

Reactome (12)

KEGG (2)

PathwayCommons (4)

WikiPathways (11)

Cytosolic sensors of pathogen-associated DNA (R-HSA-1834949)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytosolic sensors of pathogen-associated DNA	64 targets	R-HSA-1834949
Reactome	DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
Reactome	DNA Repair	306 targets	R-HSA-73894
Reactome	E3 ubiquitin ligases ubiquitinate target proteins	110 targets	R-HSA-8866654
Reactome	IRF3-mediated induction of type I IFN	13 targets	R-HSA-3270619

Name	Explore in Pharos	Explore in Source
Cytosolic sensors of pathogen-associated DNA	64 targets	R-HSA-1834949
DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
DNA Repair	306 targets	R-HSA-73894
E3 ubiquitin ligases ubiquitinate target proteins	110 targets	R-HSA-8866654
IRF3-mediated induction of type I IFN	13 targets	R-HSA-3270619

Gene Ontology Terms (64)

Functions (9)

Components (11)

Processes (44)

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1 – 9 of 9

GO Term	Evidence	Assigned by
DNA-dependent protein kinase activity	Inferred from Direct Assay (IDA)	MGI
double-stranded DNA binding	Inferred from Direct Assay (IDA)	CAFA
protein kinase activity	Inferred from Direct Assay (IDA)	CACAO
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	BHF-UCL
protein domain specific binding	Inferred from Physical Interaction (IPI)	CAFA
transcription factor binding	Inferred from Physical Interaction (IPI)	BHF-UCL
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
enzyme binding	Inferred from Electronic Annotation (IEA)	Ensembl

GWAS Traits (21)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte percentage of leukocytes	EFO_0007989	2	2	3		88.4
eosinophil percentage of leukocytes	EFO_0007991	2	2	3		84.1
mean reticulocyte volume	EFO_0010701	1	1	1		81.9
basophil percentage of leukocytes	EFO_0007992	1	2	2		78.6
mean corpuscular volume	EFO_0004526	1	1	1		75

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte percentage of leukocytes	EFO_0007989	3		88.4
eosinophil percentage of leukocytes	EFO_0007991	3		84.1
mean reticulocyte volume	EFO_0010701	1		81.9
basophil percentage of leukocytes	EFO_0007992	2		78.6
mean corpuscular volume	EFO_0004526	1		75

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative splicing
ATP-binding
Biological rhythms
Complete proteome
Disease mutation
DNA damage
DNA recombination
DNA repair

GWAS Trait Find Similar Targets

No Header	No Header
basophil count
basophil percentage of leukocytes
body height
eosinophil count
eosinophil percentage of granulocytes
eosinophil percentage of leukocytes
erythrocyte count
granulocyte percentage of myeloid white cells
hemoglobin measurement
lymphocyte percentage of leukocytes

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	protein kinase, DNA-activated, catalytic polypeptide		464165
Macaque	protein kinase, DNA-activated, catalytic polypeptide		708029
Mouse	protein kinase, DNA activated, catalytic polypeptide	MGI:104779	19090
Rat	protein kinase, DNA activated, catalytic polypeptide	RGD:1308982	360748
Dog	protein kinase, DNA-activated, catalytic polypeptide	VGNC:44989	474176

Species	Name	OMA	EggNOG	Inparanoid
Chimp	protein kinase, DNA-activated, catalytic polypeptide
Macaque	protein kinase, DNA-activated, catalytic polypeptide
Mouse	protein kinase, DNA activated, catalytic polypeptide
Rat	protein kinase, DNA activated, catalytic polypeptide
Dog	protein kinase, DNA-activated, catalytic polypeptide

Publication Statistics

PubMed Score 985.70

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PubTator Score 1068.05

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