Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002322
UniProt IDP78527
Primary gene name(s)PRKDC
Synonym gene name(s)HYRC, HYRC1
Protein nameDNA-dependent protein kinase catalytic subunit
Protein functionSerine/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(DJ recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(DJ 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:0000269|PubMed:12649176, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:9679063}.
Subcellular locationNucleus {ECO:0000269|PubMed:12231622, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:22002106}. Nucleus, nucleolus {ECO:0000269|PubMed:22002106}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P78527
Gene Ontology
(Biological Process)
Complete annatation
B cell lineage commitment [GO:0002326];
brain development [GO:0007420];
cell proliferation [GO:0008283];
cellular protein modification process [GO:0006464];
cellular response to insulin stimulus [GO:0032869];
double-strand break repair [GO:0006302];
double-strand break repair via alternative nonhomologous end joining [GO:0097681];
double-strand break repair via nonhomologous end joining [GO:0006303];
ectopic germ cell programmed cell death [GO:0035234];
heart development [GO:0007507];
immunoglobulin V(DJ recombination [GO:0033152];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cellular senescence [GO:2000773];
negative regulation of immunoglobulin production [GO:0002638];
negative regulation of protein phosphorylation [GO:0001933];
negative regulation of response to gamma radiation [GO:2001229];
peptidyl-serine phosphorylation [GO:0018105];
positive regulation of apoptotic process [GO:0043065];
positive regulation of developmental growth [GO:0048639];
positive regulation of fibroblast proliferation [GO:0048146];
positive regulation of immune system process [GO:0002684];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of type I interferon production [GO:0032481];
pro-B cell differentiation [GO:0002328];
protein destabilization [GO:0031648];
regulation of circadian rhythm [GO:0042752];
regulation of smooth muscle cell proliferation [GO:0048660];
response to activity [GO:0014823];
response to gamma radiation [GO:0010332];
rhythmic process [GO:0048511];
signal transduction involved in mitotic G1 DNA damage checkpoint [GO:0072431];
somitogenesis [GO:0001756];
spleen development [GO:0048536];
T cell differentiation in thymus [GO:0033077];
T cell lineage commitment [GO:0002360];
T cell receptor V(DJ recombination [GO:0033153];
telomere capping [GO:0016233];
thymus development [GO:0048538]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
DNA-dependent protein kinase activity [GO:0004677];
double-stranded DNA binding [GO:0003690];
poly(A RNA binding [GO:0044822];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
transcription factor binding [GO:0008134]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
DNA-dependent protein kinase-DNA ligase 4 complex [GO:0005958];
membrane [GO:0016020];
nonhomologous end joining complex [GO:0070419];
nuclear chromosome, telomeric region [GO:0000784];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
transcription factor complex [GO:0005667]
Protein-protein interaction111577
Phylogenetic treeP78527
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.8808041990555430.007587839409273430.0206135392171177
AZA vs. DISU-0.1753073996156690.4877737394200490.931429104131977
AZA vs. IL70.3639966644133150.05793199875832130.696381432075554
AZA vs. SAHA-0.02623719624873660.9141814337710340.980750611276715
DISU vs. CD3-1.068557974582430.003487800626095550.012030916850747
DISU vs. IL70.5301596484667990.03540752794094790.246203175142892
DISU vs. SAHA0.1509035904550220.6048177657329430.875272486353971
DMSO vs. AZA0.097518840926240.5590078421779231
DMSO vs. CD3-0.7924604410768570.01368363909727220.0325086989460607
DMSO vs. DISU0.2716578899153720.2649237128160340.78420724923707
DMSO vs. IL70.273482507390.127254542369390.624666489120651
DMSO vs. SAHA-0.1305083022876210.5794010878694410.855297862045298
HIV vs. Mock in Activation0.3378093230332370.5906400734797620.999983755607037
HIV vs. Mock in Latency0.1264857022308610.4419268434050050.999834320637052
IL7 vs. CD3-0.5100589879449840.1125873481431880.20770290940843
SAHA vs. CD3-0.9310550327804930.009142232321727730.023762235441262
SAHA vs. IL7-0.3930335939080330.106989662342960.299158258237393
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.14518 0.330167
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.019 0.937 0.991 0.976 0.993
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB05210 SF1126 investigational unknown unknown
DB00201 Caffeine approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

not found

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Vpu interacts with 22190034
Pr55(Gag) incorporates 25631074
Rev interacts with 22174317
integrase interacts with 10213687
Envelope surface glycoprotein gp120 complexes with 23125841
Gag-Pol complexes with 23125841
Pr55(Gag) complexes with 23125841
Tat binds 25332688
Tat phosphorylated by 21450944
Tat downregulates 16751065
Nef complexes with 23125841

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03450 Non-homologous end-joining - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)