DegronMD - P78527(PRKDC)

FUNCTION: Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:2507541, PubMed:2247066, PubMed:1597196, PubMed:8407951, PubMed:8464713, PubMed:9362500, PubMed:9139719, PubMed:10026262, PubMed:10467406, PubMed:12509254, PubMed:11889123, PubMed:14612514, PubMed:14599745, PubMed:15177042, PubMed:18644470, PubMed:26666690, PubMed:30247612, PubMed:14704337, PubMed:16397295, PubMed:26237645, PubMed:28712728). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). 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 (By similarity). 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 (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. View more >>

GO - Biological processes (BP): activation of innate immune response [GO:0002218]; B cell lineage commitment [GO:0002326]; brain development [GO:0007420]; cellular protein modification process [GO:0006464]; cellular response to DNA damage stimulus [GO:0006974]; 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(D)J recombination [GO:0033152]; innate immune response [GO:0045087]; intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630]; maturation of 5.8S rRNA [GO:0000460]; mitotic G1 DNA damage checkpoint signaling [GO:0031571]; negative regulation of apoptotic process [GO:0043066]; negative regulation of protein phosphorylation [GO:0001933]; peptidyl-serine phosphorylation [GO:0018105]; peptidyl-threonine phosphorylation [GO:0018107]; positive regulation of apoptotic process [GO:0043065]; positive regulation of double-strand break repair via nonhomologous end joining [GO:2001034]; positive regulation of erythrocyte differentiation [GO:0045648]; positive regulation of lymphocyte differentiation [GO:0045621]; positive regulation of platelet formation [GO:1905221]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of translation [GO:0045727]; pro-B cell differentiation [GO:0002328]; protein destabilization [GO:0031648]; protein phosphorylation [GO:0006468]; regulation of circadian rhythm [GO:0042752]; regulation of epithelial cell proliferation [GO:0050678]; regulation of hematopoietic stem cell differentiation [GO:1902036]; regulation of smooth muscle cell proliferation [GO:0048660]; response to gamma radiation [GO:0010332]; rhythmic process [GO:0048511]; small-subunit processome assembly [GO:0034462]; somitogenesis [GO:0001756]; T cell differentiation in thymus [GO:0033077]; T cell lineage commitment [GO:0002360]; T cell receptor V(D)J recombination [GO:0033153]; telomere capping [GO:0016233]; telomere maintenance [GO:0000723] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A2690E	TCGA-24-1422	OV	TCGA	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation altering degron motif	0.7701
p.A2690E	DO28863	OV	ICGC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation altering degron motif	0.7701
p.E3194K	TCGA-95-7948	LUAD	TCGA	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.25
p.E3194K	DO25133	LUAD	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.25
p.E3194D	TCGA-AP-A059	UCEC	TCGA	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.25
p.E3194D	TCGA-BA-5152	HNSC	TCGA	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.25
p.E3194D	DO14393	HNSC	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.25
p.E3194D	DO41361	UCEC	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.25
p.E3193Q	TCGA-D1-A17K	UCEC	TCGA	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.2222
p.E3193Q	DO42937	UCEC	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.2222
p.V2695M	TCGA-FI-A2D0	UCEC	TCGA	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation altering degron motif	0.7208
p.V2695M	DO43891	UCEC	ICGC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation altering degron motif	0.7208
p.K2701E	TCGA-MX-A5UJ	STAD	TCGA	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.2222
p.K2701E	DO48547	STAD	ICGC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.2222
p.A2680T	TCGA-QK-A6VB	HNSC	TCGA	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.0833
p.A2680T	DO219054	HNSC	ICGC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.0833
p.L3196R	TCGA-QS-A5YQ	UCEC	TCGA	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation blocking ubiquitination signal	0.75
p.L3196R	DO49073	UCEC	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation blocking ubiquitination signal	0.75
p.L3199V	DO472	BLCA	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.6765
p.L3199F	DO218404	BRCA	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.6981
p.S3190N	DO233732	GACA	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.1389
p.A2680S	DO49685	LIAD	ICGC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.0833
p.T3197S	DO228941	LICA	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.7116
p.H2681Q	DO229034	LICA	ICGC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.1111
p.E3193K	DO50753	LICA	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation rewiring degron network	0.2222
p.M3205V	DO45127	LIRI	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation blocking phosphorylation signal	0.6944
p.M3205R	DO220863	MELA	ICGC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation blocking phosphorylation signal	0.6944
p.T3198S	SIDM01004	Chronic Myelogenous Leukemia	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00557	Neuroblastoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00615	Hepatocellular Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00234	Other Solid Cancers	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM01197	Colorectal Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM01005	Acute Myeloid Leukemia	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00569	Osteosarcoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM01028	Esophageal Squamous Cell Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00466	Ovarian Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00351	Oral Cavity Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00383	Gastric Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00294	Small Cell Lung Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00214	Colorectal Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00997	Thyroid Gland Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00580	Acute Myeloid Leukemia	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00397	Acute Myeloid Leukemia	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00655	Other Solid Cancers	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM01217	Other Blood Cancers	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00306	Non-Small Cell Lung Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00361	Non-Small Cell Lung Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00996	Thyroid Gland Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM00604	Oral Cavity Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM01551	Gastric Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM01622	Breast Carcinoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.T3198S	SIDM01391	Neuroblastoma	GDSC	LTPLPE	DEG_SCF_FBW7_2	3197:3202	Mutation altering degron motif	0.8227
p.L2693W	SIDM01030	Esophageal Squamous Cell Carcinoma	GDSC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation altering degron motif	0.7015
p.L2693W	KYSE-180	oesophagus	COSMIC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation altering degron motif	0.7015
p.K2703E	SIDM00927	Small Cell Lung Carcinoma	GDSC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation blocking ubiquitination signal	0.6111
p.K2703E	NCI-H510A	lung	COSMIC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation blocking ubiquitination signal	0.6111
p.D2699N	SIDM01727	Chronic Myelogenous Leukemia	GDSC	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.2778
p.D2698N	ACH-000241	Leukemia	CCLE	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.3056
p.P2707S	ACH-000579	Skin Cancer	CCLE	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation rewiring degron network	0.0556
p.L2692W	ACH-000693	Esophageal Cancer	CCLE	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation altering degron motif	0.7015
p.K2702E	ACH-000871	Lung Cancer	CCLE	QRAPLKSVG	DEG_APCC_DBOX_1	2689:2697	Mutation blocking ubiquitination signal	0.6389

Kaplan plot for PRKDC in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PRKDC

UniProt ID: P78527

Entrez ID: 5591

Protein name: DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (p460)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PRKDC in