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Prkdc |
Protein FULL name:
DNA-dependent protein kinase catalytic subunit [Mus musculus].
Prkdc (Mus musculus) is product of expression of Prkdc gene.
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, C1D, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, SRF, 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 TP53/p53 in the presence of supercoiled DNA is dependent on C1D (By similarity).
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
ENZYME REGULATION: Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation (By similarity).
SUBUNIT: DNA-PK is a heterotrimer of PRKDC and the Ku p70-p86 (XRCC6-XRCC5) dimer. Formation of this complex may be promoted by interaction with ILF3. Associates with the DNA-bound Ku heterodimer, but it can also bind to and be activated by free DNA. Interacts with DNA-PKcs-interacting protein (KIP) with the region upstream the kinase domain. PRKDC alone also interacts with and phosphorylates DCLRE1C, thereby activating the latent endonuclease activity of this protein. Interacts with C1D (By similarity). Interacts with TTI1 and TELO2 (By similarity).
SUBCELLULAR LOCATION: Nucleus.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. Autophosphorylated on Thr-2605, Thr-2634 and Thr-2643. Thr-2605 is a DNA damage-inducible phosphorylation site (inducible with ionizing radiation, IR). Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair (By similarity).
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.
SIMILARITY: Belongs to the PI3/PI4-kinase family.
SIMILARITY: Contains 1 FAT domain.
SIMILARITY: Contains 1 FATC domain.
SIMILARITY: Contains 3 HEAT repeats.
SIMILARITY: Contains 1 PI3K/PI4K domain.
SIMILARITY: Contains 3 TPR repeats.
| NCBI GenPept GI number(s): |
124517706 |
| Species: | Mus musculus |
Links to other databases:
| Database | ID | Link |
| Uniprot | P97313 |
P97313 |
| PFAM: | - |
P97313 (Link - using uniprot id) |
| InterPro: | - |
P97313 (Link - using uniprot id) |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MAEEGTGVRCWLLQLQEFLSAADRCSAAGASYQLIRSLGQECVLSTSSAV QALQISLVFSRDFGLLVFIRKSLSIEDFRDCREEALKFLCVFLEKIDQKV MHYSLDIKNTCTSVYTKDRTAKCKIPALDLLIKLLQILRSTRLMDEFKIG ELFNKFYGELASKSKLPDTVLEKVYELLGVLGEVHPSEMINHSENLFRAF LGELKTQMTSTVREPKFPVLAGCLKGLSSLLCNFTKSMEEDPQTSKEIFG FTFKAIRPQIEMKRYAVPLAGLRLLTLHASQFTACLLDNYITLFEVLSKW CSHTNVELKKAAHSALESFLRQISFTVAEDAELHKSRLKYFMEQFYGIIR NTDSNNKELAIAIRGYGLFAGPCKVINAKDVDFMYVELIQRCKQMFLTHA DASEDHVYQMPSFLQSIASVLLYLDTVPEVYTPVLEHLMVVQIDSFPQYS PKMQLVCCKAIIKLFLALSEKGPVHWNCISAVVHQGLIRICSKPVVLQKD VESRSDNRSASEEVRTGRWKVPTYKDYVDLFQHLLGCDQMEDFILGDETF LFVNSSLKSLNHLLYDEFIRSVLKIVEKLDLTLEKQTVGEQEDGSTADVW VIPTSDPAANLHPAKPSDFSALINLVEFCREILPRKHVGFFEPWVYSFAY ELILQSTRLPLISGFYKLLSIAVKNARKIKYFEGISPKSLKHSPEDTEKY SCFALFAKFGKEVSVKMKQYKDELLASCLTFVLSLPHDIIELDVRAYVPA LQMAFKLGLSHMPLAEIGLHALKEWSVHIDKSILQPYYKDILPCLDGYLN TSTLSDETKSHWGLSALSRAAQKGFNRHVVKHLKRTRNSSPDEALSLEEI RIKVVQILGSLGGQINKSLVTATSGERMKKYVAWDAERRLSFAVPFREMK PVIYLDVFLPRVTELALSASDRQTKVAACELLHSMVMFMLGRATQMPEGQ GLPPMYQLYKHTFPVLLQLACDVDQVTRQLYEPLVMQLIHWLTNNKKFES QDTVALLEAILDGIVDPVDSTLRDFCGRCVQEFLKWSIKQTTPQQQEKSP VNSKSLFKRLYSLALHPNAFKRLGAALAFNHIYKEFREEGSLVEQFVFEA LVTYMESLALAHEDEKSLGTVQQCCDAIDHLRRIIEKKHVSLNKAKKRRL PQGFPPLTSLCLLDLVEWLLAHCGRPQTECRHKSMELFYKFVPLLPGNKS PSLWLKDLIKKKGISFLINTFEGGASSSDQPAGILAQPTLVYLQGPISLR GVLQWLDLLLAALECYNTFIEKETVQGQEVLGAEVQSSLLKSVAFFLESI ATHSARAVEQRFGSGAPGPPSLHEEEKYNYSKCTVLVRIMEFTTTLLIAS PEDCKLLEKDLCNTNLMQVLVKMICEPMSLGFNIGDVQVMNHLPSICVNL LKALRKSPYRDMLETHLKEKVTVQSVEELCSINLCSSGARQERSKLLSIL SACKQLHKAGFSHVISPSQSTALNHSVGMRLLSLVYKGIVPAEERQCLQS LDPSCKSLANGLLELAFGFGGLCDHLVSLLLNSAMLSTQYLGSSQRNISF SHGEYFYSLFSEVINSELLKNLDIAVSRLMESSSDNPKMVSTVLNGMLDT SFRDRAVQKHQGLKLATAILQNWRKCDSWWAPDSAPESKTTVLSLLAKML QIDSALSFDTNHSSFSEIFTTYASLLADTKLGLHLKGQAIILLPFFTSLR EGSLENLKHILEKLIVCNFPMKSDEFPPDSLKYNNYVDCMKKFLDALELS QSPMLFQLMTDILCREQRHIMEELFQTTFKRIARQSPCVTQLNLLESVYT MFRKADLPSNVTRQAFVDRSLLTLLWHCDLDTLKEFFSRIVVDAIDVLKS RFTKLNEFTFDTQITKKMCYYKMLAVMYSRLLKDDVHSKEAKINQAFHGS RVAEGNELTKTLLKLCHDAFTENMVGESQLLEKRRLYHCAAYNCAISLIS CVFNELKFYQGFLFNEKPEKNLFIFENLIDLKRCYTFPIEVEVPMERKKK YIEIRKEARDAANGASGSPHYMSSLSYLTDSSLSEEMSQFDFSTGVQSYS YSSQDRKPTTGHFQRREHQDSMTQDDIMELEMDELNQHECMAPMIALIKH MQRNVIAPKGEEGSIPKDLPPWMKFLHDKLGNASVSLNIRLFLAKLVINT EEVFRPYAKHWLSPLLQLAVCENNREGIHYMMVEIVATILSWTGLATPTG VPKDEVLANRLLRFLMKHVFHPKRAVFRHNLEIIKTLVECWKECLSIPYR LIFEKFSHKDPNSKDNSVGIQLLGIVIANNLPPYDPNCDITSAMYFEALV NNMSFVKYKEVYAAAAEVLGLILQYITERKHVIAELVCELVIKQLKQHQN TMEDKFIVCLNKIAKGFPPLADRFLNALFFLLPKFHGVMKTLCLEVVLCR AEEITGLYLQLKSKDFLQVMRHRDDERQKVCLDIVYKMVAKLKPIELREL LNPVVEFVSHPSPTCREQMYNILMWIHDNYRDQESQNDEDSQEIFKLAKD VLIQGLIDENVGLQLIIRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHF LSLATNFLLEMTRMSPDYLNPIFEHPLSECEFQEYTIDPDWRFRSTVLTP MFIETQASPSILHTQTQEGPLSDQRQKPGQVRATQQQYDFTPTQASVERS SFDWLTGSSIDLLADHTVFSSETLSSSLLFSHKRTEKSQRMSCKSVGPDF GTKKLGLPDDEVDNQVKSGTPSQADILRLRRRFLKDREKLSLLYAKRGLM EQKLEKDIKSEFKMKQDAQVVLYRSYRHGDLPDIQIQHSGLITPLQAVAQ KDPIIAKQLFSSLFSGILKEMNKFKTTSEKNIITQNLLQDFNRFLNTTFL FFPPFVSCIQEISCQHPDFLTLDPASVRVGCLASLQQPGGIRLLEEALLR LMPKEPPTKRVRGKTCLPPDVLRWMELAKLYRSIGEYDVLRGIFSSELGT TQDTQNALLAEARSDYCQAAKLYDEALNKLEWVDGEPTEAEKEFWELASL DCYNNLSKWKELEYCSTVNIVSENSLDLSKMWSEPFYQETYLPYVIRSKL KLLLQGEGNQSLLTFVDEAMNKELQKTVLELQYSQELSLLYILQDDIDRA TYYIKNGIQIFMQNYSSIDVLLYRSRLAKLQSVQTLAEIEEFLSFICKHG DLSSLGPLRRLLKTWTSRYPDVVTDPMHIWDDIITNRCFFLSKIEERLTA PSGDHSMSVDEDEESIDREVYEPKEDVRCMLQSCRFTMKMKMIESAWKQS NFSLSMKLLKEMHKESKTREIWRVQWLHSYSQLNHCRSHTQSPREQVLNM LKTITLLDESDISNYLNKNIQASCDQSILLGTTCRIMADALSREPACLSD LEENKVNSILTLSGSNAENTETVITGLYQRAFHHLSKAVQSAEEETQLSC WGHEAAAERAHAYMTLVGFCDQQLRKVEESASQKTSAEMEAYPALVVEKM LRALKLNSSEARLKFPRLLQIIEQYSEETLNIMTKEISSIPCWQFIGWIS HMMALLDKEEAIAVQHTVEEIADNYPQAIIYPFIISSESYSFKNTSSGHN NKAFVERIKSKLDHGEVIHSFINALDQLSNPDLLFKDWVSDTKDELGKNP VNKKNIEKLYERMYAALGDLRAPGLGPFRRRFIQAFGKEFVKSFGNGGSK LLTMKVDDFCKITGSLLVRMKKDSKLPGNLKEYSPWMSEFKAQFLKNELE IPGQYDGKSKPLPEYHVRISGFDERVKVMLSLRKPKRIVIRGHDEKEYPF LVKGGEDLRQDQRIEQIFEVMNAILSQDAACSQRNMQLRTYRVVPMTSRL GLIEWIENTMTLKDLLLSNMSQEEKVANNSDPKAPIRDYKDWLMKVSGKS DAGAYVLMYSRANRTETVVAFRRRESQVPPDLLKRAFVKMSTSPEAFLAL RSHFASSHALLCISHWLLGIGDRHLNNFMVAMETGSVIGIDFGHAFGSAT QFLPVPELMPFRLTRQFVSLMLPMKETGLMCTVMVHALRAFRSCAGLLTD TMEIFVKEPSFDWKSFEQTMLRKGGSWIQEINVTEKNWYPQHKIRYAKRK LAGANPAVITCDELYLGHEASSAFRSYTAVARGNRDYNIRAQEPESGLSE ETQVKCLVDQATDPNILGRTWEGWEPWM |
Prkdc (Mus musculus) is able to recognize following damages:
Prkdc (Mus musculus) belongs to following protein families:
References:
| Title | Authors | Journal |
| Cloning and chromosomal mapping of the mouse DNA-dependent protein kinase gene. | Hamatani K, Matsuda Y, Araki R, Itoh M, Abe M | Immunogenetics Jan. 1, 1996 |
| Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse. | Blunt T, Gell D, Fox M, Taccioli GE, Lehmann AR, Jackson SP, Jeggo PA | Proc Natl Acad Sci U S A Sept. 17, 1996 |
| Biochemical and genetic defects in the DNA-dependent protein kinase in murine scid lymphocytes. | Danska JS, Holland DP, Mariathasan S, Williams KM, Guidos CJ | Mol Cell Biol Oct. 1, 1996 |
| Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice. | Araki R, Fujimori A, Hamatani K, Mita K, Saito T, Mori M, Fukumura R, Morimyo M, Muto M, Itoh M, Tatsumi K, Abe M | Proc Natl Acad Sci U S A March 18, 1997 |
| Functional interaction between DNA-PK and c-Abl in response to DNA damage. | Kharbanda S, Pandey P, Jin S, Inoue S, Bharti A, Yuan ZM, Weichselbaum R, Weaver D, Kufe D | Nature April 17, 1997 |
| The murine DNA-PKcs gene consists of 86 exons dispersed in more than 250 kb. | Fujimori A, Araki R, Fukumura R, Saito T, Mori M, Mita K, Tatsumi K, Abe M | Genomics Oct. 1, 1997 |
| Murine cell line SX9 bearing a mutation in the dna-pkcs gene exhibits aberrant V(D)J recombination not only in the coding joint but also in the signal joint. | Fukumura R, Araki R, Fujimori A, Mori M, Saito T, Watanabe F, Sarashi M, Itsukaichi H, Eguchi-Kasai K, Sato K, Tatsumi K, Abe M | J Biol Chem May 22, 1998 |
| Mouse cdc21 only 0.5 kb upstream from dna-pkcs in a head-to-head organization: an implication of co-evolution of ATM family members and cell cycle regulating genes. | Saito T, Matsuda Y, Ishii H, Watanabe F, Mori M, Hayashi A, Araki R, Fujimori A, Fukumura R, Morimyo M, Tatsumi K, Hori T, Abe M | Mamm Genome Sept. 1, 1998 |
| Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. | Espejel S, Franco S, Sgura A, Gae D, Bailey SM, Taccioli GE, Blasco MA | EMBO J Nov. 15, 2002 |
| The transcriptional landscape of the mammalian genome. | Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y | Science Sept. 2, 2005 |
| Nonhomologous end-joining deficiency of L5178Y-S cells is not associated with mutation in the ABCDE autophosphorylation cluster. | Brzoska K, Kruszewski M, Szumiel I | Acta Biochim Pol Jan. 1, 2006 |
Last modification of this entry: Oct. 6, 2010.
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