Prkdc
entrez
19090
canonical
uniprot
P97313
canonical
ensembl
ENSMUSG00000022672
resolver
ensp
ENSMUSP00000023352
resolver
genesymbol
Prkdc
resolver
genesymbol_syn
Xrcc7
resolver
uniprot
E9QN15
resolver
uniprot
O88187
resolver
uniprot
P97928
resolver
uniprot
Q307W9
resolver
uniprot
Q3V2W8
resolver
uniprot
Q8C2A7
resolver
uniprot
Q9Z341
resolver
uniprot_entry
PRKDC_MOUSE
resolver
uniprot_sec
E9QN15
resolver
uniprot_sec
O88187
resolver
uniprot_sec
P97928
resolver
uniprot_sec
Q307W9
resolver
uniprot_sec
Q3V2W8
resolver
uniprot_sec
Q8C2A7
resolver
uniprot_sec
Q9Z341
resolver
activity_regulation
ACTIVITY REGULATION: Activity seems to be attenuated by autophosphorylation. Binding to the SL1 region of U3 small nucleolar RNA promotes auto-phosphorylation activity. Inhibited by wortmannin. {ECO:0000250|UniProtKB:P78527}.
uniprot
proteins
amino_acid_sequence
MAEEGTGVRCWLLQLQEFLSAADRCSAAGASYQLIRSLGQECVLSTSSAVQALQISLVFSRDFGLLVFIRKSLSIEDFRDCREEALKFLCVFLEKIDQKVMHYSLDIKNTCTSVYTKDRTAKCKIPALDLLIKLLQILRSTRLMDEFKIGELFNKFYGELASKSKLPDTVLEKVYELLGVLGEVHPSEMINHSENLFRAFLGELKTQMTSTVREPKFPVLAGCLKGLSSLLCNFTKSMEEDPQTSKEIFGFTFKAIRPQIEMKRYAVPLAGLRLLTLHASQFTACLLDNYITLFEVLSKWCSHTNVELKKAAHSALESFLRQISFTVAEDAELHKSRLKYFMEQFYGIIRNTDSNNKELAIAIRGYGLFAGPCKVINAKDVDFMYVELIQRCKQMFLTHADASEDHVYQMPSFLQSIASVLLYLDTVPEVYTPVLEHLMVVQIDSFPQYSPKMQLVCCKAIIKLFLALSEKGPVHWNCISAVVHQGLIRICSKPVVLQKDVESRSDNRSASEEVRTGRWKVPTYKDYVDLFQHLLGCDQMEDFILGDETFLFVNSSLKSLNHLLYDEFIRSVLKIVEKLDLTLEKQTVGEQEDGSTADVWVIPTSDPAANLHPAKPSDFSALINLVEFCREILPRKHVGFFEPWVYSFAYELILQSTRLPLISGFYKLLSIAVKNARKIKYFEGISPKSLKHSPEDTEKYSCFALFAKFGKEVSVKMKQYKDELLASCLTFVLSLPHDIIELDVRAYVPALQMAFKLGLSHMPLAEIGLHALKEWSVHIDKSILQPYYKDILPCLDGYLNTSTLSDETKSHWGLSALSRAAQKGFNRHVVKHLKRTRNSSPDEALSLEEIRIKVVQILGSLGGQINKSLVTATSGERMKKYVAWDAERRLSFAVPFREMKPVIYLDVFLPRVTELALSASDRQTKVAACELLHSMVMFMLGRATQMPEGQGLPPMYQLYKHTFPVLLQLACDVDQVTRQLYEPLVMQLIHWLTNNKKFESQDTVALLEAILDGIVDPVDSTLRDFCGRCVQEFLKWSIKQTTPQQQEKSPVNSKSLFKRLYSLALHPNAFKRLGAALAFNHIYKEFREEGSLVEQFVFEALVTYMESLALAHEDEKSLGTVQQCCDAIDHLRRIIEKKHVSLNKAKKRRLPQGFPPLTSLCLLDLVEWLLAHCGRPQTECRHKSMELFYKFVPLLPGNKSPSLWLKDLIKKKGISFLINTFEGGASSSDQPAGILAQPTLVYLQGPISLRGVLQWLDLLLAALECYNTFIEKETVQGQEVLGAEVQSSLLKSVAFFLESIATHSARAVEQRFGSGAPGPPSLHEEEKYNYSKCTVLVRIMEFTTTLLIASPEDCKLLEKDLCNTNLMQVLVKMICEPMSLGFNIGDVQVMNHLPSICVNLLKALRKSPYRDMLETHLKEKVTVQSVEELCSINLCSSGARQERSKLLSILSACKQLHKAGFSHVISPSQSTALNHSVGMRLLSLVYKGIVPAEERQCLQSLDPSCKSLANGLLELAFGFGGLCDHLVSLLLNSAMLSTQYLGSSQRNISFSHGEYFYSLFSEVINSELLKNLDIAVSRLMESSSDNPKMVSTVLNGMLDTSFRDRAVQKHQGLKLATAILQNWRKCDSWWAPDSAPESKTTVLSLLAKMLQIDSALSFDTNHSSFSEIFTTYASLLADTKLGLHLKGQAIILLPFFTSLREGSLENLKHILEKLIVCNFPMKSDEFPPDSLKYNNYVDCMKKFLDALELSQSPMLFQLMTDILCREQRHIMEELFQTTFKRIARQSPCVTQLNLLESVYTMFRKADLPSNVTRQAFVDRSLLTLLWHCDLDTLKEFFSRIVVDAIDVLKSRFTKLNEFTFDTQITKKMCYYKMLAVMYSRLLKDDVHSKEAKINQAFHGSRVAEGNELTKTLLKLCHDAFTENMVGESQLLEKRRLYHCAAYNCAISLISCVFNELKFYQGFLFNEKPEKNLFIFENLIDLKRCYTFPIEVEVPMERKKKYIEIRKEARDAANGASGSPHYMSSLSYLTDSSLSEEMSQFDFSTGVQSYSYSSQDRKPTTGHFQRREHQDSMTQDDIMELEMDELNQHECMAPMIALIKHMQRNVIAPKGEEGSIPKDLPPWMKFLHDKLGNASVSLNIRLFLAKLVINTEEVFRPYAKHWLSPLLQLAVCENNREGIHYMMVEIVATILSWTGLATPTGVPKDEVLANRLLRFLMKHVFHPKRAVFRHNLEIIKTLVECWKECLSIPYRLIFEKFSHKDPNSKDNSVGIQLLGIVIANNLPPYDPNCDITSAMYFEALVNNMSFVKYKEVYAAAAEVLGLILQYITERKHVIAELVCELVIKQLKQHQNTMEDKFIVCLNKIAKGFPPLADRFLNALFFLLPKFHGVMKTLCLEVVLCRAEEITGLYLQLKSKDFLQVMRHRDDERQKVCLDIVYKMVAKLKPIELRELLNPVVEFVSHPSPTCREQMYNILMWIHDNYRDQESQNDEDSQEIFKLAKDVLIQGLIDENVGLQLIIRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHFLSLATNFLLEMTRMSPDYLNPIFEHPLSECEFQEYTIDPDWRFRSTVLTPMFIETQASPSILHTQTQEGPLSDQRQKPGQVRATQQQYDFTPTQASVERSSFDWLTGSSIDLLADHTVFSSETLSSSLLFSHKRTEKSQRMSCKSVGPDFGTKKLGLPDDEVDNQVKSGTPSQADILRLRRRFLKDREKLSLLYAKRGLMEQKLEKDIKSEFKMKQDAQVVLYRSYRHGDLPDIQIQHSGLITPLQAVAQKDPIIAKQLFSSLFSGILKEMNKFKTTSEKNIITQNLLQDFNRFLNTTFLFFPPFVSCIQEISCQHPDFLTLDPASVRVGCLASLQQPGGIRLLEEALLRLMPKEPPTKRVRGKTCLPPDVLRWMELAKLYRSIGEYDVLRGIFSSELGTTQDTQNALLAEARSDYCQAAKLYDEALNKLEWVDGEPTEAEKEFWELASLDCYNNLSKWKELEYCSTVNIVSENSLDLSKMWSEPFYQETYLPYVIRSKLKLLLQGEGNQSLLTFVDEAMNKELQKTVLELQYSQELSLLYILQDDIDRATYYIKNGIQIFMQNYSSIDVLLYRSRLAKLQSVQTLAEIEEFLSFICKHGDLSSLGPLRRLLKTWTSRYPDVVTDPMHIWDDIITNRCFFLSKIEERLTAPSGDHSMSVDEDEESIDREVYEPKEDVRCMLQSCRFTMKMKMIESAWKQSNFSLSMKLLKEMHKESKTREIWRVQWLHSYSQLNHCRSHTQSPREQVLNMLKTITLLDESDISNYLNKNIQASCDQSILLGTTCRIMADALSREPACLSDLEENKVNSILTLSGSNAENTETVITGLYQRAFHHLSKAVQSAEEETQLSCWGHEAAAERAHAYMTLVGFCDQQLRKVEESASQKTSAEMEAYPALVVEKMLRALKLNSSEARLKFPRLLQIIEQYSEETLNIMTKEISSIPCWQFIGWISHMMALLDKEEAIAVQHTVEEIADNYPQAIIYPFIISSESYSFKNTSSGHNNKAFVERIKSKLDHGEVIHSFINALDQLSNPDLLFKDWVSDTKDELGKNPVNKKNIEKLYERMYAALGDLRAPGLGPFRRRFIQAFGKEFVKSFGNGGSKLLTMKVDDFCKITGSLLVRMKKDSKLPGNLKEYSPWMSEFKAQFLKNELEIPGQYDGKSKPLPEYHVRISGFDERVKVMLSLRKPKRIVIRGHDEKEYPFLVKGGEDLRQDQRIEQIFEVMNAILSQDAACSQRNMQLRTYRVVPMTSRLGLIEWIENTMTLKDLLLSNMSQEEKVANNSDPKAPIRDYKDWLMKVSGKSDAGAYVLMYSRANRTETVVAFRRRESQVPPDLLKRAFVKMSTSPEAFLALRSHFASSHALLCISHWLLGIGDRHLNNFMVAMETGSVIGIDFGHAFGSATQFLPVPELMPFRLTRQFVSLMLPMKETGLMCTVMVHALRAFRSCAGLLTDTMEIFVKEPSFDWKSFEQTMLRKGGSWIQEINVTEKNWYPQHKIRYAKRKLAGANPAVITCDELYLGHEASSAFRSYTAVARGNRDYNIRAQEPESGLSEETQVKCLVDQATDPNILGRTWEGWEPWM
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Prkdc are the cause of severe combined immune deficiency (SCID) which is characterized by a lack of mature functional lymphocytes and a high susceptibility to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency syndrome in human infants. {ECO:0000269|PubMed:9122213}.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (By similarity). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (By similarity). Must be bound to DNA to express its catalytic properties (By similarity). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (By similarity). 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 (By similarity). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (By similarity). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (By similarity). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (PubMed:12426399). Also involved in modulation of transcription (By similarity). 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 (By similarity). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (By similarity). Recognizes the substrate consensus sequence [ST]-Q (By similarity). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (By similarity). Phosphorylates ASF1A, 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 (By similarity). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (By similarity). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (By similarity). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (By similarity). 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 (PubMed:24158435). 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 (By similarity). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (By similarity). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (By similarity). {ECO:0000250|UniProtKB:P78527, ECO:0000269|PubMed:12426399, ECO:0000269|PubMed:24158435}.
uniprot
proteins
mass_dalton
471471
uniprot
proteins
mutagenesis
MUTAGEN 2026; /note="S->A: Normal erythrocyte and platelet numbers; when associated with A-2038 and 2050-A--A-2053."; /evidence="ECO:0000269|PubMed:32103174"; MUTAGEN 2038; /note="S->A: Normal erythrocyte and platelet numbers; when associated with A-2026 and 2050-A--A-2053."; /evidence="ECO:0000269|PubMed:32103174"; MUTAGEN 2050..2053; /note="SYSS->AYAA: Normal erythrocyte and platelet numbers; when associated with A-2026 and A-2038."; /evidence="ECO:0000269|PubMed:32103174"; MUTAGEN 2605; /note="T->A: Lethal at 4-week-old; impaired hematopoiesis due to a decrease in hematopoietic stem and progenitor cells which causes a severe reduction in the numbers of erythrocytes, platelets, lymphocytes and neutrophils; reduced protein synthesis in bone marrow and fetal erythrocyte precursors; normal V(D)J recombination in B-cells; when associated with 2614-A--A-2616, A-2634 and A-2643."; /evidence="ECO:0000269|PubMed:32103174"; MUTAGEN 2614..2616; /note="TQT->AQA: Lethal at 4-week-old; impaired hematopoiesis due to a decrease in hematopoietic stem and progenitor cells which causes a severe reduction in the numbers of erythrocytes, platelets, lymphocytes and neutrophils; reduced protein synthesis in bone marrow and fetal erythrocyte precursors; normal V(D)J recombination in B-cells; when associated with A-2605, A-2634 and A-2643."; /evidence="ECO:0000269|PubMed:32103174"; MUTAGEN 2634; /note="T->A: Lethal at 4-week-old; impaired hematopoiesis due to a decrease in hematopoietic stem and progenitor cells which causes a severe reduction in the numbers of erythrocytes, platelets, lymphocytes and neutrophils; reduced protein synthesis in bone marrow and fetal erythrocyte precursors; normal V(D)J recombination in B-cells; when associated with A-2605, 2614-A--A-2616 and A-2643."; /evidence="ECO:0000269|PubMed:32103174"; MUTAGEN 2643; /note="T->A: Lethal at 4-week-old; impaired hematopoiesis due to a decrease in hematopoietic stem and progenitor cells which causes a severe reduction in the numbers of erythrocytes, platelets, lymphocytes and neutrophils; reduced protein synthesis in bone marrow and fetal erythrocyte precursors; normal V(D)J recombination in B-cells; when associated with A-2605, 2614-A--A-2616 and A-2634."; /evidence="ECO:0000269|PubMed:32103174"; MUTAGEN 3922; /note="D->A: Probable loss of catalytic activity. Severe reduction in the number of hematopoietic stem and progenitor cells in fetal liver. Slight reduction in translation during erythrocyte development in fetal liver."; /evidence="ECO:0000269|PubMed:32103174
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated at two clusters, the T2609 cluster and the S2056 cluster (PubMed:24158435, PubMed:32103174). Autophosphorylated on Ser-2053, Thr-2605, Thr-2634 and Thr-2643. Ser-2053 and Thr-2605 are DNA damage-inducible phosphorylation sites (inducible with ionizing radiation, IR) dephosphorylated by PPP5C (PubMed:24158435, PubMed:32103174). Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair (By similarity). Autophosphorylation in trans within DNA-PK complexes loaded on DNA ends leads to the dissociation of PRKDC from DNA and the transition into the short-range NHEJ complex (By similarity). Autophosphorylation of the T2609 cluster is required for hematopoietic development and protein synthesis in erythrocytes precursors (PubMed:32103174). {ECO:0000250|UniProtKB:P78527, ECO:0000269|PubMed:24158435, ECO:0000269|PubMed:32103174}.; PTM: S-nitrosylated by GAPDH. {ECO:0000269|PubMed:20972425}.; PTM: Polyubiquitinated by RNF144A, leading to proteasomal degradation. {ECO:0000250|UniProtKB:P78527}.
uniprot
proteins
protein_family
PI3/PI4-kinase family
uniprot
proteins
pubmed
12426399
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16404475
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20972425
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
24158435
uniprot
proteins
pubmed
32103174
uniprot
proteins
pubmed
8816463
uniprot
proteins
pubmed
8816792
uniprot
proteins
pubmed
8881030
uniprot
proteins
pubmed
9109492
uniprot
proteins
pubmed
9122213
uniprot
proteins
pubmed
9339376
uniprot
proteins
pubmed
9582343
uniprot
proteins
pubmed
9716665
uniprot
proteins
sequence_length
4128
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P78527}. Nucleus, nucleolus {ECO:0000250|UniProtKB:P78527}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P78527}.
uniprot
proteins