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Names & Taxonomy

Uniprot ID:: P78527
Entry Name:: PRKDC_HUMAN
Status:: reviewed
Protein Names:: DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (p460)
Gene Names:: PRKDC HYRC HYRC1
Gene Names Primary:: PRKDC
Organism:: Homo sapiens (Human)

Structure

Length:: 4128
Sequence:: MAGSGAGVRCSLLRLQETLSAADRCGAALAGHQLIRGLGQECVLSSSPAVLALQTSLVFSRDFGLLVFVRKSLNSIEFRECREEILKFLCIFLEKMGQKIAPYSVEIKNTCTSVYTKDRAAKCKIPALDLLIKLLQTFRSSRLMDEFKIGELFSKFYGELALKKKIPDTVLEKVYELLGLLGEVHPSEMINNAENLFRAFLGELKTQMTSAVREPKLPVLAGCLKGLSSLLCNFTKSMEEDPQTSREIFNFVLKAIRPQIDLKRYAVPSAGLRLFALHASQFSTCLLDNYVSLFEVLLKWCAHTNVELKKAALSALESFLKQVSNMVAKNAEMHKNKLQYFMEQFYGIIRNVDSNNKELSIAIRGYGLFAGPCKVINAKDVDFMYVELIQRCKQMFLTQTDTGDDRVYQMPSFLQSVASVLLYLDTVPEVYTPVLEHLVVMQIDSFPQYSPKMQLVCCRAIVKVFLALAAKGPVLRNCISTVVHQGLIRICSKPVVLPKGPESESEDHRASGEVRTGKWKVPTYKDYVDLFRHLLSSDQMMDSILADEAFFSVNSSSESLNHLLYDEFVKSVLKIVEKLDLTLEIQTVGEQENGDEAPGVWMIPTSDPAANLHPAKPKDFSAFINLVEFCREILPEKQAEFFEPWVYSFSYELILQSTRLPLISGFYKLLSITVRNAKKIKYFEGVSPKSLKHSPEDPEKYSCFALFVKFGKEVAVKMKQYKDELLASCLTFLLSLPHNIIELDVRAYVPALQMAFKLGLSYTPLAEVGLNALEEWSIYIDRHVMQPYYKDILPCLDGYLKTSALSDETKNNWEVSALSRAAQKGFNKVVLKHLKKTKNLSSNEAISLEEIRIRVVQMLGSLGGQINKNLLTVTSSDEMMKSYVAWDREKRLSFAVPFREMKPVIFLDVFLPRVTELALTASDRQTKVAACELLHSMVMFMLGKATQMPEGGQGAPPMYQLYKRTFPVLLRLACDVDQVTRQLYEPLVMQLIHWFTNNKKFESQDTVALLEAILDGIVDPVDSTLRDFCGRCIREFLKWSIKQITPQQQEKSPVNTKSLFKRLYSLALHPNAFKRLGASLAFNNIYREFREEESLVEQFVFEALVIYMESLALAHADEKSLGTIQQCCDAIDHLCRIIEKKHVSLNKAKKRRLPRGFPPSASLCLLDLVKWLLAHCGRPQTECRHKSIELFYKFVPLLPGNRSPNLWLKDVLKEEGVSFLINTFEGGGCGQPSGILAQPTLLYLRGPFSLQATLCWLDLLLAALECYNTFIGERTVGALQVLGTEAQSSLLKAVAFFLESIAMHDIIAAEKCFGTGAAGNRTSPQEGERYNYSKCTVVVRIMEFTTTLLNTSPEGWKLLKKDLCNTHLMRVLVQTLCEPASIGFNIGDVQVMAHLPDVCVNLMKALKMSPYKDILETHLREKITAQSIEELCAVNLYGPDAQVDRSRLAAVVSACKQLHRAGLLHNILPSQSTDLHHSVGTELLSLVYKGIAPGDERQCLPSLDLSCKQLASGLLELAFAFGGLCERLVSLLLNPAVLSTASLGSSQGSVIHFSHGEYFYSLFSETINTELLKNLDLAVLELMQSSVDNTKMVSAVLNGMLDQSFRERANQKHQGLKLATTILQHWKKCDSWWAKDSPLETKMAVLALLAKILQIDSSVSFNTSHGSFPEVFTTYISLLADTKLDLHLKGQAVTLLPFFTSLTGGSLEELRRVLEQLIVAHFPMQSREFPPGTPRFNNYVDCMKKFLDALELSQSPMLLELMTEVLCREQQHVMEELFQSSFRRIARRGSCVTQVGLLESVYEMFRKDDPRLSFTRQSFVDRSLLTLLWHCSLDALREFFSTIVVDAIDVLKSRFTKLNESTFDTQITKKMGYYKILDVMYSRLPKDDVHAKESKINQVFHGSCITEGNELTKTLIKLCYDAFTENMAGENQLLERRRLYHCAAYNCAISVICCVFNELKFYQGFLFSEKPEKNLLIFENLIDLKRRYNFPVEVEVPMERKKKYIEIRKEAREAANGDSDGPSYMSSLSYLADSTLSEEMSQFDFSTGVQSYSYSSQDPRPATGRFRRREQRDPTVHDDVLELEMDELNRHECMAPLTALVKHMHRSLGPPQGEEDSVPRDLPSWMKFLHGKLGNPIVPLNIRLFLAKLVINTEEVFRPYAKHWLSPLLQLAASENNGGEGIHYMVVEIVATILSWTGLATPTGVPKDEVLANRLLNFLMKHVFHPKRAVFRHNLEIIKTLVECWKDCLSIPYRLIFEKFSGKDPNSKDNSVGIQLLGIVMANDLPPYDPQCGIQSSEYFQALVNNMSFVRYKEVYAAAAEVLGLILRYVMERKNILEESLCELVAKQLKQHQNTMEDKFIVCLNKVTKSFPPLADRFMNAVFFLLPKFHGVLKTLCLEVVLCRVEGMTELYFQLKSKDFVQVMRHRDDERQKVCLDIIYKMMPKLKPVELRELLNPVVEFVSHPSTTCREQMYNILMWIHDNYRDPESETDNDSQEIFKLAKDVLIQGLIDENPGLQLIIRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHFLSLATNFLLEMTSMSPDYPNPMFEHPLSECEFQEYTIDSDWRFRSTVLTPMFVETQASQGTLQTRTQEGSLSARWPVAGQIRATQQQHDFTLTQTADGRSSFDWLTGSSTDPLVDHTSPSSDSLLFAHKRSERLQRAPLKSVGPDFGKKRLGLPGDEVDNKVKGAAGRTDLLRLRRRFMRDQEKLSLMYARKGVAEQKREKEIKSELKMKQDAQVVLYRSYRHGDLPDIQIKHSSLITPLQAVAQRDPIIAKQLFSSLFSGILKEMDKFKTLSEKNNITQKLLQDFNRFLNTTFSFFPPFVSCIQDISCQHAALLSLDPAAVSAGCLASLQQPVGIRLLEEALLRLLPAELPAKRVRGKARLPPDVLRWVELAKLYRSIGEYDVLRGIFTSEIGTKQITQSALLAEARSDYSEAAKQYDEALNKQDWVDGEPTEAEKDFWELASLDCYNHLAEWKSLEYCSTASIDSENPPDLNKIWSEPFYQETYLPYMIRSKLKLLLQGEADQSLLTFIDKAMHGELQKAILELHYSQELSLLYLLQDDVDRAKYYIQNGIQSFMQNYSSIDVLLHQSRLTKLQSVQALTEIQEFISFISKQGNLSSQVPLKRLLNTWTNRYPDAKMDPMNIWDDIITNRCFFLSKIEEKLTPLPEDNSMNVDQDGDPSDRMEVQEQEEDISSLIRSCKFSMKMKMIDSARKQNNFSLAMKLLKELHKESKTRDDWLVSWVQSYCRLSHCRSRSQGCSEQVLTVLKTVSLLDENNVSSYLSKNILAFRDQNILLGTTYRIIANALSSEPACLAEIEEDKARRILELSGSSSEDSEKVIAGLYQRAFQHLSEAVQAAEEEAQPPSWSCGPAAGVIDAYMTLADFCDQQLRKEEENASVIDSAELQAYPALVVEKMLKALKLNSNEARLKFPRLLQIIERYPEETLSLMTKEISSVPCWQFISWISHMVALLDKDQAVAVQHSVEEITDNYPQAIVYPFIISSESYSFKDTSTGHKNKEFVARIKSKLDQGGVIQDFINALDQLSNPELLFKDWSNDVRAELAKTPVNKKNIEKMYERMYAALGDPKAPGLGAFRRKFIQTFGKEFDKHFGKGGSKLLRMKLSDFNDITNMLLLKMNKDSKPPGNLKECSPWMSDFKVEFLRNELEIPGQYDGRGKPLPEYHVRIAGFDERVTVMASLRRPKRIIIRGHDEREHPFLVKGGEDLRQDQRVEQLFQVMNGILAQDSACSQRALQLRTYSVVPMTSRLGLIEWLENTVTLKDLLLNTMSQEEKAAYLSDPRAPPCEYKDWLTKMSGKHDVGAYMLMYKGANRTETVTSFRKRESKVPADLLKRAFVRMSTSPEAFLALRSHFASSHALICISHWILGIGDRHLNNFMVAMETGGVIGIDFGHAFGSATQFLPVPELMPFRLTRQFINLMLPMKETGLMYSIMVHALRAFRSDPGLLTNTMDVFVKEPSFDWKNFEQKMLKKGGSWIQEINVAEKNWYPRQKICYAKRKLAGANPAVITCDELLLGHEKAPAFRDYVAVARGSKDHNIRAQEPESGLSEETQVKCLMDQATDPNILGRTWEGWEPWM
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Nucleus

Function

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 -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.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:: ENZYME REGULATION: Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation.
Cross Reference Drug Bank:: DB00201
Gene Ontology Go:: cytosol
DNA-dependent protein kinase-DNA ligase 4 complex
membrane
nonhomologous end joining complex
nuclear chromosome, telomeric region
nucleolus
nucleoplasm
transcription factor complex
ATP binding
DNA-dependent protein kinase activity
double-stranded DNA binding
poly(A) RNA binding
protein kinase activity
protein serine/threonine kinase activity
transcription factor binding
B cell lineage commitment
brain development
cell proliferation
cellular protein modification process
cellular response to insulin stimulus
DNA repair
double-strand break repair
double-strand break repair via alternative nonhomologous end joining
double-strand break repair via nonhomologous end joining
ectopic germ cell programmed cell death
heart development
immunoglobulin V(D)J recombination
innate immune response
intrinsic apoptotic signaling pathway in response to DNA damage
negative regulation of apoptotic process
negative regulation of cellular senescence
negative regulation of immunoglobulin production
negative regulation of protein phosphorylation
negative regulation of response to gamma radiation
peptidyl-serine phosphorylation
positive regulation of apoptotic process
positive regulation of developmental growth
positive regulation of fibroblast proliferation
positive regulation of immune system process
positive regulation of transcription from RNA polymerase II promoter
positive regulation of type I interferon production
pro-B cell differentiation
protein destabilization
regulation of circadian rhythm
regulation of smooth muscle cell proliferation
response to activity
response to gamma radiation
rhythmic process
signal transduction involved in mitotic G1 DNA damage checkpoint
somitogenesis
spleen development
T cell differentiation in thymus
T cell lineage commitment
T cell receptor V(D)J recombination
telomere capping
thymus development
Gene Ontology Biological Process:: B cell lineage commitment
brain development
cell proliferation
cellular protein modification process
cellular response to insulin stimulus
DNA repair
double-strand break repair
double-strand break repair via alternative nonhomologous end joining
double-strand break repair via nonhomologous end joining
ectopic germ cell programmed cell death
heart development
immunoglobulin V(D)J recombination
innate immune response
intrinsic apoptotic signaling pathway in response to DNA damage
negative regulation of apoptotic process
negative regulation of cellular senescence
negative regulation of immunoglobulin production
negative regulation of protein phosphorylation
negative regulation of response to gamma radiation
peptidyl-serine phosphorylation
positive regulation of apoptotic process
positive regulation of developmental growth
positive regulation of fibroblast proliferation
positive regulation of immune system process
positive regulation of transcription from RNA polymerase II promoter
positive regulation of type I interferon production
pro-B cell differentiation
protein destabilization
regulation of circadian rhythm
regulation of smooth muscle cell proliferation
response to activity
response to gamma radiation
rhythmic process
signal transduction involved in mitotic G1 DNA damage checkpoint
somitogenesis
spleen development
T cell differentiation in thymus
T cell lineage commitment
T cell receptor V(D)J recombination
telomere capping
thymus development
Gene Ontology Molecular Function:: ATP binding
DNA-dependent protein kinase activity
double-stranded DNA binding
poly(A) RNA binding
protein kinase activity
protein serine/threonine kinase activity
transcription factor binding
Gene Ontology Cellular Component:: cytosol
DNA-dependent protein kinase-DNA ligase 4 complex
membrane
nonhomologous end joining complex
nuclear chromosome, telomeric region
nucleolus
nucleoplasm
transcription factor complex
Keywords:: ATP-binding
Acetylation
Alternative splicing
Biological rhythms
Complete proteome
DNA damage
DNA recombination
DNA repair
DNA-binding
Disease mutation
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
SCID
Serine/threonine-protein kinase
TPR repeat
Transferase
Ubl conjugation
Interacts With:: O43918; P42575; P14921; P50549; P09629; P17936; Q9BPZ7; Q96RI1-2; Q9HB75; P10276; P17947; P13010; P12956; P25490

Names & Taxonomy

Structure

Subcellular location

Function

Publication