ID PRKDC_MOUSE Reviewed; 4128 AA. AC P97313; E9QN15; O88187; P97928; Q307W9; Q3V2W8; Q8C2A7; Q9Z341; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 27-MAR-2024, entry version 210. DE RecName: Full=DNA-dependent protein kinase catalytic subunit; DE Short=DNA-PK catalytic subunit; DE Short=DNA-PKcs; DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P78527}; DE AltName: Full=p460; GN Name=Prkdc; Synonyms=Xrcc7; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN SCID, VARIANT RP CYS-2140, AND VARIANT SCID 4046-TYR--MET-4128 DEL. RC STRAIN=C.B17; TISSUE=Fibroblast, and Leukocyte; RX PubMed=9122213; DOI=10.1073/pnas.94.6.2438; RA Araki R., Fujimori A., Hamatani K., Mita K., Saito T., Mori M., RA Fukumura R., Morimyo M., Muto M., Itoh M., Tatsumi K., Abe M.; RT "Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase RT catalytic subunit of severe combined immune deficiency mice."; RL Proc. Natl. Acad. Sci. U.S.A. 94:2438-2443(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT CYS-2140. RX PubMed=9582343; DOI=10.1074/jbc.273.21.13058; RA Fukumura R., Araki R., Fujimori A., Mori M., Saito T., Watanabe F., RA Sarashi M., Itsukaichi H., Eguch-Kasai K., Sato K., Tatsumi K., Abe M.; RT "Murine cell line SX9 bearing a mutation in the DNA-PKcs gene exhibits RT aberrant V(D)J recombination not only in the coding joint but also in the RT signal joint."; RL J. Biol. Chem. 273:13058-13064(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-2140. RC STRAIN=129/SvJ; RX PubMed=9339376; DOI=10.1006/geno.1997.4919; RA Fujimori A., Araki R., Fukumura R., Saito T., Mori M., Mita K., Tatsumi K., RA Abe M.; RT "The murine DNA-PKcs gene consists of 86 exons dispersed in more than 250 RT kb."; RL Genomics 45:194-199(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 3618-4128. RC STRAIN=C57BL/6J, and NOD; TISSUE=Heart, and Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26. RX PubMed=9716665; DOI=10.1007/s003359900861; RA Saito T., Matsuda Y., Ishii H., Watanabe F., Mori M., Hayashi A., Araki R., RA Fujimori A., Fukumura R., Morimyo M., Tatsumi K., Hori T., Abe M.; RT "Mouse Cdc21 only 0.5 kb upstream from DNA-PKcs in a head-to-head RT organization: an implication of co-evolution of ATM family members and cell RT cycle regulating genes."; RL Mamm. Genome 9:769-772(1998). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2550-2658. RX PubMed=16404475; RA Brzoska K., Kruszewski M., Szumiel I.; RT "Nonhomologous end-joining deficiency of L5178Y-S cells is not associated RT with mutation in the ABCDE autophosphorylation cluster."; RL Acta Biochim. Pol. 53:233-236(2006). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3615-4128. RC STRAIN=BALB/cJ; TISSUE=Leukocyte; RX PubMed=8881030; DOI=10.1007/s002510050159; RA Hamatani K., Matsuda Y., Araki R., Itoh M., Abe M.; RT "Cloning and chromosomal mapping of the mouse DNA-dependent protein kinase RT gene."; RL Immunogenetics 45:1-5(1996). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3680-4128. RX PubMed=8816792; DOI=10.1073/pnas.93.19.10285; RA Blunt T., Gell D., Fox M., Taccioli G.E., Lehmann A.R., Jackson S.P., RA Jeggo P.A.; RT "Identification of a nonsense mutation in the carboxyl-terminal region of RT DNA-dependent protein kinase catalytic subunit in the scid mouse."; RL Proc. Natl. Acad. Sci. U.S.A. 93:10285-10290(1996). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3839-4128. RC STRAIN=C.B17; RX PubMed=8816463; DOI=10.1128/mcb.16.10.5507; RA Danska J.S., Holland D.P., Mariathasan S., Williams K.M., Guidos C.J.; RT "Biochemical and genetic defects in the DNA-dependent protein kinase in RT murine scid lymphocytes."; RL Mol. Cell. Biol. 16:5507-5517(1996). RN [11] RP PHOSPHORYLATION OF ABL1. RX PubMed=9109492; DOI=10.1038/386732a0; RA Kharbanda S., Pandey P., Jin S., Inoue S., Bharti A., Yuan Z.-M., RA Weichselbaum R., Weaver D., Kufe D.; RT "Functional interaction between DNA-PK and c-Abl in response to DNA RT damage."; RL Nature 386:732-735(1997). RN [12] RP FUNCTION. RX PubMed=12426399; DOI=10.1093/emboj/cdf593; RA Espejel S., Franco S., Sgura A., Gae D., Bailey S.M., Taccioli G.E., RA Blasco M.A.; RT "Functional interaction between DNA-PKcs and telomerase in telomere length RT maintenance."; RL EMBO J. 21:6275-6287(2002). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Spleen, and RC Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [14] RP S-NITROSYLATION BY GAPDH. RX PubMed=20972425; DOI=10.1038/ncb2114; RA Kornberg M.D., Sen N., Hara M.R., Juluri K.R., Nguyen J.V., Snowman A.M., RA Law L., Hester L.D., Snyder S.H.; RT "GAPDH mediates nitrosylation of nuclear proteins."; RL Nat. Cell Biol. 12:1094-1100(2010). RN [15] RP FUNCTION IN CIRCADIAN CLOCK, AND INTERACTION WITH CRY1 AND CRY2. RX PubMed=24158435; DOI=10.1074/jbc.m113.509604; RA Gao P., Yoo S.H., Lee K.J., Rosensweig C., Takahashi J.S., Chen B.P., RA Green C.B.; RT "Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian RT period length."; RL J. Biol. Chem. 288:35277-35286(2013). RN [16] RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-2026; SER-2038; RP 2050-SER--SER-2053; THR-2605; 2614-THR--THR-2616; THR-2634; THR-2643 AND RP ASP-3922. RX PubMed=32103174; DOI=10.1038/s41586-020-2041-2; RA Shao Z., Flynn R.A., Crowe J.L., Zhu Y., Liang J., Jiang W., Aryan F., RA Aoude P., Bertozzi C.R., Estes V.M., Lee B.J., Bhagat G., Zha S., Calo E.; RT "DNA-PKcs has KU-dependent function in rRNA processing and RT haematopoiesis."; RL Nature 579:291-296(2020). CC -!- FUNCTION: Serine/threonine-protein kinase that acts as a molecular CC sensor for DNA damage (By similarity). Involved in DNA non-homologous CC end joining (NHEJ) required for double-strand break (DSB) repair and CC V(D)J recombination (By similarity). Must be bound to DNA to express CC its catalytic properties (By similarity). Promotes processing of CC hairpin DNA structures in V(D)J recombination by activation of the CC hairpin endonuclease artemis (DCLRE1C) (By similarity). Recruited by CC XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align CC broken ends of DNA, thereby preventing their degradation, (2) and CC sequester the DSB for repair by NHEJ (By similarity). Act as a scaffold CC protein to aid the localization of DNA repair proteins to the site of CC damage (By similarity). The assembly of the DNA-PK complex at DNA ends CC is also required for the NHEJ ligation step (By similarity). Found at CC the ends of chromosomes, suggesting a further role in the maintenance CC of telomeric stability and the prevention of chromosomal end fusion CC (PubMed:12426399). Also involved in modulation of transcription (By CC similarity). As part of the DNA-PK complex, involved in the early steps CC of ribosome assembly by promoting the processing of precursor rRNA into CC mature 18S rRNA in the small-subunit processome (By similarity). CC Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the CC small-subunit processome (By similarity). Recognizes the substrate CC consensus sequence [ST]-Q (By similarity). Phosphorylates 'Ser-139' of CC histone variant H2AX, thereby regulating DNA damage response mechanism CC (By similarity). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, CC HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, CC XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (By similarity). Can CC phosphorylate C1D not only in the presence of linear DNA but also in CC the presence of supercoiled DNA (By similarity). Ability to CC phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent CC on C1D (By similarity). Contributes to the determination of the CC circadian period length by antagonizing phosphorylation of CRY1 'Ser- CC 588' and increasing CRY1 protein stability, most likely through an CC indirect mechanism (PubMed:24158435). Plays a role in the regulation of CC DNA virus-mediated innate immune response by assembling into the HDP- CC RNP complex, a complex that serves as a platform for IRF3 CC phosphorylation and subsequent innate immune response activation CC through the cGAS-STING pathway (By similarity). Also regulates the CC cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby CC impairing CGAS oligomerization and activation (By similarity). Also CC regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 CC (By similarity). {ECO:0000250|UniProtKB:P78527, CC ECO:0000269|PubMed:12426399, ECO:0000269|PubMed:24158435}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000250|UniProtKB:P78527}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P78527}; CC -!- ACTIVITY REGULATION: Activity seems to be attenuated by CC autophosphorylation. Binding to the SL1 region of U3 small nucleolar CC RNA promotes auto-phosphorylation activity. Inhibited by wortmannin. CC {ECO:0000250|UniProtKB:P78527}. CC -!- SUBUNIT: DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed CC of XRCC6/Ku70 and XRCC5/Ku86). Formation of this complex may be CC promoted by interaction with ILF3. Component of the core long-range CC non-homologous end joining (NHEJ) complex (also named DNA-PK complex) CC composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. CC Additional component of the NHEJ complex includes PAXX. Following CC autophosphorylation, PRKDC dissociates from DNA. Interacts with DNA- CC PKcs-interacting protein (KIP) with the region upstream the kinase CC domain. PRKDC alone also interacts with and phosphorylates DCLRE1C, CC thereby activating the latent endonuclease activity of this protein. CC Interacts with C1D. Interacts with TTI1 and TELO2. Interacts with CIB1. CC Interacts with SETX. Interacts with NR4A3; the DNA-dependent protein CC kinase complex DNA-PK phosphorylates and activates NR4A3 and prevents CC NR4A3 ubiquitination and degradation. Interacts with BRAT1. Part of the CC HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, CC paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 CC RNA. Interacts with KAT5. {ECO:0000250|UniProtKB:P78527}. CC -!- INTERACTION: CC P97313; P00533: EGFR; Xeno; NbExp=4; IntAct=EBI-2272005, EBI-297353; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P78527}. Nucleus, CC nucleolus {ECO:0000250|UniProtKB:P78527}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=A number of isoforms are produced.; CC Name=1; CC IsoId=P97313-1; Sequence=Displayed; CC Name=2; CC IsoId=P97313-2; Sequence=VSP_017361, VSP_017362; CC -!- PTM: Autophosphorylated at two clusters, the T2609 cluster and the CC S2056 cluster (PubMed:24158435, PubMed:32103174). Autophosphorylated on CC Ser-2053, Thr-2605, Thr-2634 and Thr-2643. Ser-2053 and Thr-2605 are CC DNA damage-inducible phosphorylation sites (inducible with ionizing CC radiation, IR) dephosphorylated by PPP5C (PubMed:24158435, CC PubMed:32103174). Autophosphorylation induces a conformational change CC that leads to remodeling of the DNA-PK complex, requisite for efficient CC end processing and DNA repair (By similarity). Autophosphorylation in CC trans within DNA-PK complexes loaded on DNA ends leads to the CC dissociation of PRKDC from DNA and the transition into the short-range CC NHEJ complex (By similarity). Autophosphorylation of the T2609 cluster CC is required for hematopoietic development and protein synthesis in CC erythrocytes precursors (PubMed:32103174). CC {ECO:0000250|UniProtKB:P78527, ECO:0000269|PubMed:24158435, CC ECO:0000269|PubMed:32103174}. CC -!- PTM: S-nitrosylated by GAPDH. {ECO:0000269|PubMed:20972425}. CC -!- PTM: Polyubiquitinated by RNF144A, leading to proteasomal degradation. CC {ECO:0000250|UniProtKB:P78527}. CC -!- DISEASE: Note=Defects in Prkdc are the cause of severe combined immune CC deficiency (SCID) which is characterized by a lack of mature functional CC lymphocytes and a high susceptibility to lethal opportunistic CC infections if not chronically treated with antibiotics. The lack of CC B- and T-cell immunity resembles severe combined immunodeficiency CC syndrome in human infants. {ECO:0000269|PubMed:9122213}. CC -!- DISRUPTION PHENOTYPE: Viable. Normal number of erythrocytes and CC platelets. Normal translation levels in erythrocyte precursors. CC {ECO:0000269|PubMed:32103174}. CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D87521; BAA19566.1; -; mRNA. DR EMBL; AB007544; BAA28873.1; -; mRNA. DR EMBL; AB011543; BAA28875.1; -; mRNA. DR EMBL; AB030754; BAB91149.1; -; Genomic_DNA. DR EMBL; AK084827; BAE43387.1; -; mRNA. DR EMBL; AK088981; BAC40685.1; -; mRNA. DR EMBL; AC111103; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC154586; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CT010522; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CT030649; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB000629; BAA34640.1; -; Genomic_DNA. DR EMBL; DQ235257; ABB36568.1; -; mRNA. DR EMBL; DQ235258; ABB36569.1; -; mRNA. DR EMBL; D83786; BAA12115.1; -; mRNA. DR EMBL; U78157; AAB36939.1; -; mRNA. DR EMBL; U78158; AAB36940.1; -; mRNA. DR CCDS; CCDS27978.1; -. [P97313-1] DR PIR; JC6306; JC6306. DR RefSeq; NP_035289.2; NM_011159.2. [P97313-1] DR SMR; P97313; -. DR BioGRID; 202371; 13. DR ComplexPortal; CPX-3424; DNA-dependent protein kinase complex. DR CORUM; P97313; -. DR IntAct; P97313; 7. DR MINT; P97313; -. DR STRING; 10090.ENSMUSP00000023352; -. DR BindingDB; P97313; -. DR ChEMBL; CHEMBL2176779; -. DR GuidetoPHARMACOLOGY; 2800; -. DR iPTMnet; P97313; -. DR PhosphoSitePlus; P97313; -. DR EPD; P97313; -. DR MaxQB; P97313; -. DR PaxDb; 10090-ENSMUSP00000023352; -. DR PeptideAtlas; P97313; -. DR ProteomicsDB; 289411; -. [P97313-1] DR ProteomicsDB; 289412; -. [P97313-2] DR Pumba; P97313; -. DR Antibodypedia; 52433; 1802 antibodies from 44 providers. DR DNASU; 19090; -. DR Ensembl; ENSMUST00000023352.9; ENSMUSP00000023352.8; ENSMUSG00000022672.9. [P97313-1] DR GeneID; 19090; -. DR KEGG; mmu:19090; -. DR UCSC; uc007yhs.1; mouse. [P97313-2] DR UCSC; uc007yht.1; mouse. [P97313-1] DR AGR; MGI:104779; -. DR CTD; 5591; -. DR MGI; MGI:104779; Prkdc. DR VEuPathDB; HostDB:ENSMUSG00000022672; -. DR eggNOG; KOG0891; Eukaryota. DR GeneTree; ENSGT00940000155633; -. DR HOGENOM; CLU_224534_0_0_1; -. DR InParanoid; P97313; -. DR OMA; PSPMCRE; -. DR OrthoDB; 8448at2759; -. DR PhylomeDB; P97313; -. DR TreeFam; TF324494; -. DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ). DR Reactome; R-MMU-8866654; E3 ubiquitin ligases ubiquitinate target proteins. DR BioGRID-ORCS; 19090; 14 hits in 117 CRISPR screens. DR ChiTaRS; Prkdc; mouse. DR PRO; PR:P97313; -. DR Proteomes; UP000000589; Chromosome 16. DR RNAct; P97313; Protein. DR Bgee; ENSMUSG00000022672; Expressed in olfactory tubercle and 256 other cell types or tissues. DR GO; GO:0000785; C:chromatin; ISO:MGI. DR GO; GO:0070418; C:DNA-dependent protein kinase complex; ISO:MGI. DR GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; ISS:UniProtKB. DR GO; GO:0070419; C:nonhomologous end joining complex; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0032993; C:protein-DNA complex; ISO:MGI. DR GO; GO:0032040; C:small-subunit processome; ISS:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004677; F:DNA-dependent protein kinase activity; IDA:MGI. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:MGI. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0035979; F:histone H2AXS139 kinase activity; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI. DR GO; GO:0004672; F:protein kinase activity; ISO:MGI. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0034511; F:U3 snoRNA binding; ISS:UniProtKB. DR GO; GO:0002218; P:activation of innate immune response; ISO:MGI. DR GO; GO:0002326; P:B cell lineage commitment; IMP:MGI. DR GO; GO:0007420; P:brain development; IGI:MGI. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI. DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB. DR GO; GO:0006302; P:double-strand break repair; IMP:MGI. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:MGI. DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IMP:MGI. DR GO; GO:0007507; P:heart development; IGI:MGI. DR GO; GO:0002327; P:immature B cell differentiation; IMP:MGI. DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IMP:MGI. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI. DR GO; GO:0030098; P:lymphocyte differentiation; IMP:MGI. DR GO; GO:0000460; P:maturation of 5.8S rRNA; ISS:UniProtKB. DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI. DR GO; GO:2000773; P:negative regulation of cellular senescence; ISO:MGI. DR GO; GO:0160049; P:negative regulation of cGAS/STING signaling pathway; ISO:MGI. DR GO; GO:0002638; P:negative regulation of immunoglobulin production; ISO:MGI. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB. DR GO; GO:2001229; P:negative regulation of response to gamma radiation; ISO:MGI. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI. DR GO; GO:0048639; P:positive regulation of developmental growth; ISO:MGI. DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; ISS:UniProtKB. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI. DR GO; GO:0002684; P:positive regulation of immune system process; ISO:MGI. DR GO; GO:0045621; P:positive regulation of lymphocyte differentiation; IMP:UniProtKB. DR GO; GO:1905221; P:positive regulation of platelet formation; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB. DR GO; GO:0002328; P:pro-B cell differentiation; IMP:MGI. DR GO; GO:0031648; P:protein destabilization; IDA:MGI. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; ISO:MGI. DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; IMP:UniProtKB. DR GO; GO:0048660; P:regulation of smooth muscle cell proliferation; ISS:UniProtKB. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IMP:MGI. DR GO; GO:0010212; P:response to ionizing radiation; IMP:MGI. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0034462; P:small-subunit processome assembly; ISS:UniProtKB. DR GO; GO:0001756; P:somitogenesis; IGI:MGI. DR GO; GO:0048536; P:spleen development; ISO:MGI. DR GO; GO:0033077; P:T cell differentiation in thymus; IMP:MGI. DR GO; GO:0002360; P:T cell lineage commitment; IMP:MGI. DR GO; GO:0033153; P:T cell receptor V(D)J recombination; IMP:MGI. DR GO; GO:0016233; P:telomere capping; ISO:MGI. DR GO; GO:0000723; P:telomere maintenance; IMP:MGI. DR GO; GO:0048538; P:thymus development; ISO:MGI. DR GO; GO:0033151; P:V(D)J recombination; IGI:MGI. DR CDD; cd05172; PIKKc_DNA-PK; 1. DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR037706; DNA-PK_dom. DR InterPro; IPR046804; DNA-PKcs_N. DR InterPro; IPR046803; DNAPKcs_CC1-2. DR InterPro; IPR012582; DNAPKcs_CC3. DR InterPro; IPR045581; DNAPKcs_CC5. DR InterPro; IPR003152; FATC_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000403; PI3/4_kinase_cat_dom. DR InterPro; IPR036940; PI3/4_kinase_cat_sf. DR InterPro; IPR018936; PI3/4_kinase_CS. DR InterPro; IPR003151; PIK-rel_kinase_FAT. DR InterPro; IPR014009; PIK_FAT. DR PANTHER; PTHR11139; ATAXIA TELANGIECTASIA MUTATED ATM -RELATED; 1. DR PANTHER; PTHR11139:SF68; DNA-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT; 1. DR Pfam; PF20500; DNA-PKcs_N; 1. DR Pfam; PF20502; DNAPKcs_CC1-2; 1. DR Pfam; PF08163; DNAPKcs_CC3; 1. DR Pfam; PF19704; DNAPKcs_CC5; 1. DR Pfam; PF02259; FAT; 1. DR Pfam; PF02260; FATC; 1. DR Pfam; PF00454; PI3_PI4_kinase; 1. DR SMART; SM01343; FATC; 1. DR SMART; SM01344; NUC194; 1. DR SMART; SM00146; PI3Kc; 1. DR SUPFAM; SSF48371; ARM repeat; 3. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51189; FAT; 1. DR PROSITE; PS51190; FATC; 1. DR PROSITE; PS00915; PI3_4_KINASE_1; 1. DR PROSITE; PS00916; PI3_4_KINASE_2; 1. DR PROSITE; PS50290; PI3_4_KINASE_3; 1. DR Genevisible; P97313; MM. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Biological rhythms; KW Disease variant; DNA damage; DNA repair; Immunity; Innate immunity; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Ribosome biogenesis; S-nitrosylation; SCID; KW Serine/threonine-protein kinase; TPR repeat; Transferase; Ubl conjugation. FT CHAIN 1..4128 FT /note="DNA-dependent protein kinase catalytic subunit" FT /id="PRO_0000225599" FT REPEAT 288..323 FT /note="HEAT 1" FT REPEAT 1001..1037 FT /note="HEAT 2" FT REPEAT 1050..1086 FT /note="HEAT 3" FT REPEAT 1720..1753 FT /note="TPR 1" FT DOMAIN 2907..3539 FT /note="FAT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534" FT REPEAT 2921..2954 FT /note="TPR 2" FT REPEAT 2956..2983 FT /note="TPR 3" FT DOMAIN 3722..4053 FT /note="PI3K/PI4K catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT DOMAIN 4096..4128 FT /note="FATC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534, FT ECO:0000255|PROSITE-ProRule:PRU00535" FT REGION 1501..1536 FT /note="Interaction with C1D" FT /evidence="ECO:0000250|UniProtKB:P78527" FT REGION 1501..1536 FT /note="Leucine-zipper" FT REGION 2049..2071 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2432..3213 FT /note="KIP-binding" FT /evidence="ECO:0000250|UniProtKB:P78527" FT REGION 2614..2635 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2738..2766 FT /note="May split the end of the DNA molecule, with the two FT strands separating around the region" FT /evidence="ECO:0000250|UniProtKB:P78527" FT REGION 3728..3734 FT /note="G-loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 3919..3927 FT /note="Catalytic loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 3939..3964 FT /note="Activation loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT SITE 2017..2018 FT /note="Cleavage; by caspase-3" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 117 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 511 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 840 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 891 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 1062 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 1206 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 1967 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 2053 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 2255 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 2531 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 2605 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 2608 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 2634 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 2643 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 3206 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 3241 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 3260 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 3638 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 3642 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 3731 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 3821 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT MOD_RES 4026 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78527" FT VAR_SEQ 842..852 FT /note="DEALSLEEIRI -> VRNPFLILYLK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_017361" FT VAR_SEQ 853..4128 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_017362" FT VARIANT 2140 FT /note="R -> C" FT /evidence="ECO:0000269|PubMed:9122213, FT ECO:0000269|PubMed:9339376, ECO:0000269|PubMed:9582343" FT VARIANT 3191 FT /note="L -> P" FT VARIANT 4046..4128 FT /note="Missing (in SCID)" FT /evidence="ECO:0000269|PubMed:9122213" FT MUTAGEN 2026 FT /note="S->A: Normal erythrocyte and platelet numbers; when FT associated with A-2038 and 2050-A--A-2053." FT /evidence="ECO:0000269|PubMed:32103174" FT MUTAGEN 2038 FT /note="S->A: Normal erythrocyte and platelet numbers; when FT associated with A-2026 and 2050-A--A-2053." FT /evidence="ECO:0000269|PubMed:32103174" FT MUTAGEN 2050..2053 FT /note="SYSS->AYAA: Normal erythrocyte and platelet numbers; FT when associated with A-2026 and A-2038." FT /evidence="ECO:0000269|PubMed:32103174" FT MUTAGEN 2605 FT /note="T->A: Lethal at 4-week-old; impaired hematopoiesis FT due to a decrease in hematopoietic stem and progenitor FT cells which causes a severe reduction in the numbers of FT erythrocytes, platelets, lymphocytes and neutrophils; FT reduced protein synthesis in bone marrow and fetal FT erythrocyte precursors; normal V(D)J recombination in FT B-cells; when associated with 2614-A--A-2616, A-2634 and FT A-2643." FT /evidence="ECO:0000269|PubMed:32103174" FT MUTAGEN 2614..2616 FT /note="TQT->AQA: Lethal at 4-week-old; impaired FT hematopoiesis due to a decrease in hematopoietic stem and FT progenitor cells which causes a severe reduction in the FT numbers of erythrocytes, platelets, lymphocytes and FT neutrophils; reduced protein synthesis in bone marrow and FT fetal erythrocyte precursors; normal V(D)J recombination in FT B-cells; when associated with A-2605, A-2634 and A-2643." FT /evidence="ECO:0000269|PubMed:32103174" FT MUTAGEN 2634 FT /note="T->A: Lethal at 4-week-old; impaired hematopoiesis FT due to a decrease in hematopoietic stem and progenitor FT cells which causes a severe reduction in the numbers of FT erythrocytes, platelets, lymphocytes and neutrophils; FT reduced protein synthesis in bone marrow and fetal FT erythrocyte precursors; normal V(D)J recombination in FT B-cells; when associated with A-2605, 2614-A--A-2616 and FT A-2643." FT /evidence="ECO:0000269|PubMed:32103174" FT MUTAGEN 2643 FT /note="T->A: Lethal at 4-week-old; impaired hematopoiesis FT due to a decrease in hematopoietic stem and progenitor FT cells which causes a severe reduction in the numbers of FT erythrocytes, platelets, lymphocytes and neutrophils; FT reduced protein synthesis in bone marrow and fetal FT erythrocyte precursors; normal V(D)J recombination in FT B-cells; when associated with A-2605, 2614-A--A-2616 and FT A-2634." FT /evidence="ECO:0000269|PubMed:32103174" FT MUTAGEN 3922 FT /note="D->A: Probable loss of catalytic activity. Severe FT reduction in the number of hematopoietic stem and FT progenitor cells in fetal liver. Slight reduction in FT translation during erythrocyte development in fetal liver." FT /evidence="ECO:0000269|PubMed:32103174" FT CONFLICT 3300 FT /note="M -> T (in Ref. 1; BAA19566, 2; BAA28873/BAA28875 FT and 3; BAB91149)" FT /evidence="ECO:0000305" FT CONFLICT 3844 FT /note="M -> V (in Ref. 10; AAB36939/AAB36940)" FT /evidence="ECO:0000305" SQ SEQUENCE 4128 AA; 471471 MW; B143922D57F4331E CRC64; MAEEGTGVRC WLLQLQEFLS AADRCSAAGA SYQLIRSLGQ ECVLSTSSAV QALQISLVFS RDFGLLVFIR KSLSIEDFRD CREEALKFLC VFLEKIDQKV MHYSLDIKNT CTSVYTKDRT AKCKIPALDL LIKLLQILRS TRLMDEFKIG ELFNKFYGEL ASKSKLPDTV LEKVYELLGV LGEVHPSEMI NHSENLFRAF LGELKTQMTS TVREPKFPVL AGCLKGLSSL LCNFTKSMEE DPQTSKEIFG FTFKAIRPQI EMKRYAVPLA GLRLLTLHAS QFTACLLDNY ITLFEVLSKW CSHTNVELKK AAHSALESFL RQISFTVAED AELHKSRLKY FMEQFYGIIR NTDSNNKELA IAIRGYGLFA GPCKVINAKD VDFMYVELIQ RCKQMFLTHA DASEDHVYQM PSFLQSIASV LLYLDTVPEV YTPVLEHLMV VQIDSFPQYS PKMQLVCCKA IIKLFLALSE KGPVHWNCIS AVVHQGLIRI CSKPVVLQKD VESRSDNRSA SEEVRTGRWK VPTYKDYVDL FQHLLGCDQM EDFILGDETF LFVNSSLKSL NHLLYDEFIR SVLKIVEKLD LTLEKQTVGE QEDGSTADVW VIPTSDPAAN LHPAKPSDFS ALINLVEFCR EILPRKHVGF FEPWVYSFAY ELILQSTRLP LISGFYKLLS IAVKNARKIK YFEGISPKSL KHSPEDTEKY SCFALFAKFG KEVSVKMKQY KDELLASCLT FVLSLPHDII ELDVRAYVPA LQMAFKLGLS HMPLAEIGLH ALKEWSVHID KSILQPYYKD ILPCLDGYLN TSTLSDETKS HWGLSALSRA AQKGFNRHVV KHLKRTRNSS PDEALSLEEI RIKVVQILGS LGGQINKSLV TATSGERMKK YVAWDAERRL SFAVPFREMK PVIYLDVFLP RVTELALSAS DRQTKVAACE LLHSMVMFML GRATQMPEGQ GLPPMYQLYK HTFPVLLQLA CDVDQVTRQL YEPLVMQLIH WLTNNKKFES QDTVALLEAI LDGIVDPVDS TLRDFCGRCV QEFLKWSIKQ TTPQQQEKSP VNSKSLFKRL YSLALHPNAF KRLGAALAFN HIYKEFREEG SLVEQFVFEA LVTYMESLAL AHEDEKSLGT VQQCCDAIDH LRRIIEKKHV SLNKAKKRRL PQGFPPLTSL CLLDLVEWLL AHCGRPQTEC RHKSMELFYK FVPLLPGNKS PSLWLKDLIK KKGISFLINT FEGGASSSDQ PAGILAQPTL VYLQGPISLR GVLQWLDLLL AALECYNTFI EKETVQGQEV LGAEVQSSLL KSVAFFLESI ATHSARAVEQ RFGSGAPGPP SLHEEEKYNY SKCTVLVRIM EFTTTLLIAS PEDCKLLEKD LCNTNLMQVL VKMICEPMSL GFNIGDVQVM NHLPSICVNL LKALRKSPYR DMLETHLKEK VTVQSVEELC SINLCSSGAR QERSKLLSIL SACKQLHKAG FSHVISPSQS TALNHSVGMR LLSLVYKGIV PAEERQCLQS LDPSCKSLAN GLLELAFGFG GLCDHLVSLL LNSAMLSTQY LGSSQRNISF SHGEYFYSLF SEVINSELLK NLDIAVSRLM ESSSDNPKMV STVLNGMLDT SFRDRAVQKH QGLKLATAIL QNWRKCDSWW APDSAPESKT TVLSLLAKML QIDSALSFDT NHSSFSEIFT TYASLLADTK LGLHLKGQAI ILLPFFTSLR EGSLENLKHI LEKLIVCNFP MKSDEFPPDS LKYNNYVDCM KKFLDALELS QSPMLFQLMT DILCREQRHI MEELFQTTFK RIARQSPCVT QLNLLESVYT MFRKADLPSN VTRQAFVDRS LLTLLWHCDL DTLKEFFSRI VVDAIDVLKS RFTKLNEFTF DTQITKKMCY YKMLAVMYSR LLKDDVHSKE AKINQAFHGS RVAEGNELTK TLLKLCHDAF TENMVGESQL LEKRRLYHCA AYNCAISLIS CVFNELKFYQ GFLFNEKPEK NLFIFENLID LKRCYTFPIE VEVPMERKKK YIEIRKEARD AANGASGSPH YMSSLSYLTD SSLSEEMSQF DFSTGVQSYS YSSQDRKPTT GHFQRREHQD SMTQDDIMEL EMDELNQHEC MAPMIALIKH MQRNVIAPKG EEGSIPKDLP PWMKFLHDKL GNASVSLNIR LFLAKLVINT EEVFRPYAKH WLSPLLQLAV CENNREGIHY MMVEIVATIL SWTGLATPTG VPKDEVLANR LLRFLMKHVF HPKRAVFRHN LEIIKTLVEC WKECLSIPYR LIFEKFSHKD PNSKDNSVGI QLLGIVIANN LPPYDPNCDI TSAMYFEALV NNMSFVKYKE VYAAAAEVLG LILQYITERK HVIAELVCEL VIKQLKQHQN TMEDKFIVCL NKIAKGFPPL ADRFLNALFF LLPKFHGVMK TLCLEVVLCR AEEITGLYLQ LKSKDFLQVM RHRDDERQKV CLDIVYKMVA KLKPIELREL LNPVVEFVSH PSPTCREQMY NILMWIHDNY RDQESQNDED SQEIFKLAKD VLIQGLIDEN VGLQLIIRNF WSHETRLPSN TLDRLLALNS LYSPKIEVHF LSLATNFLLE MTRMSPDYLN PIFEHPLSEC EFQEYTIDPD WRFRSTVLTP MFIETQASPS ILHTQTQEGP LSDQRQKPGQ VRATQQQYDF TPTQASVERS SFDWLTGSSI DLLADHTVFS SETLSSSLLF SHKRTEKSQR MSCKSVGPDF GTKKLGLPDD EVDNQVKSGT PSQADILRLR RRFLKDREKL SLLYAKRGLM EQKLEKDIKS EFKMKQDAQV VLYRSYRHGD LPDIQIQHSG LITPLQAVAQ KDPIIAKQLF SSLFSGILKE MNKFKTTSEK NIITQNLLQD FNRFLNTTFL FFPPFVSCIQ EISCQHPDFL TLDPASVRVG CLASLQQPGG IRLLEEALLR LMPKEPPTKR VRGKTCLPPD VLRWMELAKL YRSIGEYDVL RGIFSSELGT TQDTQNALLA EARSDYCQAA KLYDEALNKL EWVDGEPTEA EKEFWELASL DCYNNLSKWK ELEYCSTVNI VSENSLDLSK MWSEPFYQET YLPYVIRSKL KLLLQGEGNQ SLLTFVDEAM NKELQKTVLE LQYSQELSLL YILQDDIDRA TYYIKNGIQI FMQNYSSIDV LLYRSRLAKL QSVQTLAEIE EFLSFICKHG DLSSLGPLRR LLKTWTSRYP DVVTDPMHIW DDIITNRCFF LSKIEERLTA PSGDHSMSVD EDEESIDREV YEPKEDVRCM LQSCRFTMKM KMIESAWKQS NFSLSMKLLK EMHKESKTRE IWRVQWLHSY SQLNHCRSHT QSPREQVLNM LKTITLLDES DISNYLNKNI QASCDQSILL GTTCRIMADA LSREPACLSD LEENKVNSIL TLSGSNAENT ETVITGLYQR AFHHLSKAVQ SAEEETQLSC WGHEAAAERA HAYMTLVGFC DQQLRKVEES ASQKTSAEME AYPALVVEKM LRALKLNSSE ARLKFPRLLQ IIEQYSEETL NIMTKEISSI PCWQFIGWIS HMMALLDKEE AIAVQHTVEE IADNYPQAII YPFIISSESY SFKNTSSGHN NKAFVERIKS KLDHGEVIHS FINALDQLSN PDLLFKDWVS DTKDELGKNP VNKKNIEKLY ERMYAALGDL RAPGLGPFRR RFIQAFGKEF VKSFGNGGSK LLTMKVDDFC KITGSLLVRM KKDSKLPGNL KEYSPWMSEF KAQFLKNELE IPGQYDGKSK PLPEYHVRIS GFDERVKVML SLRKPKRIVI RGHDEKEYPF LVKGGEDLRQ DQRIEQIFEV MNAILSQDAA CSQRNMQLRT YRVVPMTSRL GLIEWIENTM TLKDLLLSNM SQEEKVANNS DPKAPIRDYK DWLMKVSGKS DAGAYVLMYS RANRTETVVA FRRRESQVPP DLLKRAFVKM STSPEAFLAL RSHFASSHAL LCISHWLLGI GDRHLNNFMV AMETGSVIGI DFGHAFGSAT QFLPVPELMP FRLTRQFVSL MLPMKETGLM CTVMVHALRA FRSCAGLLTD TMEIFVKEPS FDWKSFEQTM LRKGGSWIQE INVTEKNWYP QHKIRYAKRK LAGANPAVIT CDELYLGHEA SSAFRSYTAV ARGNRDYNIR AQEPESGLSE ETQVKCLVDQ ATDPNILGRT WEGWEPWM //