PRKDC_MOUSE
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 03-AUG-2022, entry version 201.
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).
CC {ECO:0000250|UniProtKB:P78527, ECO:0000269|PubMed:12426399,
CC 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}.
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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; P97313; -.
DR PeptideAtlas; P97313; -.
DR PRIDE; P97313; -.
DR ProteomicsDB; 289411; -. [P97313-1]
DR ProteomicsDB; 289412; -. [P97313-2]
DR Antibodypedia; 52433; 1594 antibodies from 44 providers.
DR DNASU; 19090; -.
DR Ensembl; ENSMUST00000023352; ENSMUSP00000023352; ENSMUSG00000022672. [P97313-1]
DR GeneID; 19090; -.
DR KEGG; mmu:19090; -.
DR UCSC; uc007yhs.1; mouse. [P97313-2]
DR UCSC; uc007yht.1; mouse. [P97313-1]
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; GIQIFMQ; -.
DR OrthoDB; 26975at2759; -.
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 111 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 253 other tissues.
DR Genevisible; P97313; MM.
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; ISO:MGI.
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: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:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
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: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:0006468; P:protein phosphorylation; ISO: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; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR037706; DNA-PK_dom.
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 Pfam; PF19704; DNAPKcs_CC5; 1.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF08163; NUC194; 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; SSF48371; 3.
DR SUPFAM; SSF56112; SSF56112; 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.
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 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 B-
FT cells; when associated with 2614-A--A-2616, A-2634 and A-
FT 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 B-
FT cells; when associated with A-2605, 2614-A--A-2616 and A-
FT 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 B-
FT cells; when associated with A-2605, 2614-A--A-2616 and A-
FT 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
