Regulatory Network in Protein Phosphorylation
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Kinase: DNAPK protein kinase, DNA-activated, catalytic polypeptide

Group: Atypical      Family: PIKK      Subfamily: DNAPK

Description: protein kinase, DNA-activated, catalytic polypeptide

Gene Symbol: PRKDC

Synonyms: DNAPK, DNPK1, HYRC, HYRC1, XRCC7, p350

UniprotKB/SwissProt: PRKDC_HUMAN (P78527)

Function: Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA nonhomologous 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, c-myc/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 TP53/p53 in the presence of supercoiled DNA is dependent on C1D.

Subcellular Localization: Nucleus.

Protein Domain:

The substrate proteins of kinase DNAPK

No.Gene NameUniProtKB IDProtein DescriptionNumber of kinase-specific phosphorylation sitesView
1LIG4DNL4_HUMANDNA ligase 4 (EC 6.5.1.1) (DNA ligase IV) (Polydeoxyribonucleotidesynthase [ATP] 4). 2Show
2NR3C1GCR_HUMANGlucocorticoid receptor (GR) (Nuclear receptor subfamily 3 group Cmember 1). 2Show
3H2AFXH2AX_HUMANHistone H2A.x (H2a/x). 1Show
4HSP90AA1HS90A_HUMANHeat shock protein HSP 90-alpha (HSP 86) (Renal carcinoma antigen NY-REN-38). 5Show
5JUNJUN_HUMANTranscription factor AP-1 (Activator protein 1) (AP1) (Proto-oncogenec-jun) (V-jun avian sarcoma virus 17 oncogene homolog) (p39). 2Show
6XRCC6KU70_HUMANATP-dependent DNA helicase 2 subunit 1 (ATP-dependent DNA helicase II70 kDa subunit) (Lupus Ku autoantigen protein p70) (Ku70) (70 kDasubunit of Ku antigen) (Thyroid-lupus autoantigen) (TLAA) (CTC box-binding factor 75 kDa subunit) (CTCBF) (CTC75) (DNA-repair proteinXRCC6). 2Show
7XRCC5KU86_HUMANATP-dependent DNA helicase 2 subunit 2 (EC 3.6.1.-) (ATP-dependent DNAhelicase II 80 kDa subunit) (Lupus Ku autoantigen protein p86) (Ku86)(Ku80) (86 kDa subunit of Ku antigen) (Thyroid-lupus autoantigen)(TLAA) (CTC box-binding factor 85 kDa subunit) (CTCBF) (CTC85)(Nuclear factor IV) (DNA-repair protein XRCC5). 4Show
8TP53P53_HUMANCellular tumor antigen p53 (Tumor suppressor p53) (Phosphoprotein p53)(Antigen NY-CO-13). 7Show
9PRKDCPRKDC_HUMANDNA-dependent protein kinase catalytic subunit (EC 2.7.11.1) (DNA-PKcatalytic subunit) (DNA-PKcs) (DNPK1) (p460). 13Show
10RPA2RFA2_HUMANReplication protein A 32 kDa subunit (RP-A) (RF-A) (Replicationfactor-A protein 2) (p32) (p34). 11Show
11SRFSRF_HUMANSerum response factor (SRF). 6Show
12XPAXPA_HUMANDNA-repair protein complementing XP-A cells (Xeroderma pigmentosumgroup A-complementing protein). 2Show
13XRCC1XRCC1_HUMANDNA-repair protein XRCC1 (X-ray repair cross-complementing protein 1). 1Show
14XRCC4XRCC4_HUMANDNA-repair protein XRCC4 (X-ray repair cross-complementing protein 4). 2Show



The substrate proteins of kinase family DNAPK

No.Gene NameUniProtKB IDProtein DescriptionNumber of kinase family-specific phosphorylated sitesView
1LIG4DNL4_HUMANDNA ligase 4 (EC 6.5.1.1) (DNA ligase IV) (Polydeoxyribonucleotidesynthase [ATP] 4). 2Show
2NR3C1GCR_HUMANGlucocorticoid receptor (GR) (Nuclear receptor subfamily 3 group Cmember 1). 2Show
3H2AFXH2AX_HUMANHistone H2A.x (H2a/x). 1Show
4HSP90AA1HS90A_HUMANHeat shock protein HSP 90-alpha (HSP 86) (Renal carcinoma antigen NY-REN-38). 5Show
5JUNJUN_HUMANTranscription factor AP-1 (Activator protein 1) (AP1) (Proto-oncogenec-jun) (V-jun avian sarcoma virus 17 oncogene homolog) (p39). 2Show
6XRCC6KU70_HUMANATP-dependent DNA helicase 2 subunit 1 (ATP-dependent DNA helicase II70 kDa subunit) (Lupus Ku autoantigen protein p70) (Ku70) (70 kDasubunit of Ku antigen) (Thyroid-lupus autoantigen) (TLAA) (CTC box-binding factor 75 kDa subunit) (CTCBF) (CTC75) (DNA-repair proteinXRCC6). 2Show
7XRCC5KU86_HUMANATP-dependent DNA helicase 2 subunit 2 (EC 3.6.1.-) (ATP-dependent DNAhelicase II 80 kDa subunit) (Lupus Ku autoantigen protein p86) (Ku86)(Ku80) (86 kDa subunit of Ku antigen) (Thyroid-lupus autoantigen)(TLAA) (CTC box-binding factor 85 kDa subunit) (CTCBF) (CTC85)(Nuclear factor IV) (DNA-repair protein XRCC5). 4Show
8TP53P53_HUMANCellular tumor antigen p53 (Tumor suppressor p53) (Phosphoprotein p53)(Antigen NY-CO-13). 7Show
9PRKDCPRKDC_HUMANDNA-dependent protein kinase catalytic subunit (EC 2.7.11.1) (DNA-PKcatalytic subunit) (DNA-PKcs) (DNPK1) (p460). 13Show
10RPA2RFA2_HUMANReplication protein A 32 kDa subunit (RP-A) (RF-A) (Replicationfactor-A protein 2) (p32) (p34). 11Show
11SRFSRF_HUMANSerum response factor (SRF). 6Show
12XPAXPA_HUMANDNA-repair protein complementing XP-A cells (Xeroderma pigmentosumgroup A-complementing protein). 2Show
13XRCC1XRCC1_HUMANDNA-repair protein XRCC1 (X-ray repair cross-complementing protein 1). 1Show
14XRCC4XRCC4_HUMANDNA-repair protein XRCC4 (X-ray repair cross-complementing protein 4). 2Show