InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKDC

Summary

InnateDB Protein

IDBP-20942.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKDC

Protein Name

protein kinase, DNA-activated, catalytic polypeptide

Synonyms

DNA-PKcs; DNAPK; DNPK1; HYRC; HYRC1; IMD26; p350; XRCC7;

Species

Homo sapiens

Ensembl Protein

ENSP00000313420

InnateDB Gene

IDBG-408612 (PRKDC)

Protein Structure

UniProt Annotation

Function

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 machanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation. {ECO:0000269PubMed:12649176, ECO:0000269PubMed:14734805, ECO:0000269PubMed:15574326, ECO:0000269PubMed:9679063}.

Subcellular Localization

Nucleus. Nucleus, nucleolus.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 298 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	298 [view]
Protein-Protein	293 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0003677	DNA binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004677	DNA-dependent protein kinase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0016740	transferase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0019899	enzyme binding
GO:0044822	poly(A) RNA binding

Biological Process

GO:0000723	telomere maintenance
GO:0001756	somitogenesis
GO:0001933	negative regulation of protein phosphorylation
GO:0002326	B cell lineage commitment
GO:0002328	pro-B cell differentiation
GO:0002360	T cell lineage commitment
GO:0006281	DNA repair
GO:0006302	double-strand break repair
GO:0006303	double-strand break repair via nonhomologous end joining
GO:0006310	DNA recombination
GO:0006464	cellular protein modification process
GO:0006915	apoptotic process
GO:0007420	brain development
GO:0007507	heart development
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010332	response to gamma radiation
GO:0010552	positive regulation of gene-specific transcription from RNA polymerase II promoter
GO:0018105	peptidyl-serine phosphorylation
GO:0030098	lymphocyte differentiation
GO:0031648	protein destabilization
GO:0032481	positive regulation of type I interferon production
GO:0032869	cellular response to insulin stimulus
GO:0033077	T cell differentiation in thymus
GO:0033152	immunoglobulin V(D)J recombination
GO:0033153	T cell receptor V(D)J recombination
GO:0035234	ectopic germ cell programmed cell death
GO:0042752	regulation of circadian rhythm
GO:0043065	positive regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048511	rhythmic process
GO:0072431	signal transduction involved in mitotic G1 DNA damage checkpoint

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005730	nucleolus
GO:0005829	cytosol
GO:0005958	DNA-dependent protein kinase-DNA ligase 4 complex
GO:0016020	membrane
GO:0070419	nonhomologous end joining complex

Protein Structure and Domains

PDB ID

InterPro

IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR003151 PIK-related kinase, FAT
IPR003152 PIK-related kinase, FATC
IPR011009 Protein kinase-like domain
IPR012582 NUC194
IPR014009 PIK-related kinase
IPR016024 Armadillo-type fold

PFAM

PF00454
PF02259
PF02260
PF08163

PRINTS

PIRSF

SMART

SM00146

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P78527