prkdc

DNA-dependent protein kinase catalytic subunit

4146 amino acids

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. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism (By similarity).

Belongs to the PI3/PI4-kinase family.

473.505 kDa

MLLAGAGGSSGDGQDGVASGPAESAAGILGRLHQLHGLLSLESGVGAEGAHSLLHNLAEECLVSALGSSALDLNTSLIFSKEFGLLAFVRKSLSSDEFKDCREEALKFLYTFLEKIGSNVQPYAMDIKTLCVIVYTKDRAAKCKIPSLELLIKLLQLLKNSIIIEEFKIGEIFNKFYGELATKSKLSDTVLEKVYELLGILGEVQPCEMTYNSEKLFKAFLGELKAQMNSSTRNPKFPVIAGCLKGLSALMINFTKTMEEDPRTSKEIFDYTVKAISPQVEMKRYAVPSAGLNLLALHASQFSSYLMDDYQSLFEVISKWCGHTNGEMKKLAFAALDSFLKQIAHLVASDAETHKNKLHFFMEQFYEIIRKMDSSNKELSIAIRGYGLFAAPCKAVNAKNVDLMYIELIQRCKQMYLTEADTEEDNVYQLPNFLQSVASVILHMDSIPEVYTPILERLLVVQIDSFPQYSLKMQSSCCKAVLKVFLSLAGKGPVLWSLISTVVHQGLIRVCSKPVVLAQDGKEGSEAETAAATGEVRAGKWKVPTYKDYLDLFRNLLRCDQLKDSIFSDEIFSTVNSPLQSLNRLLYDELMKSILKIIEKLDLSLQKQDTGQEDDGGINNLLINATSDPAGNLYATKPKDFTAFVNLVEFCSEILPKEHIEYFESWVYVFGYELVLQSTRLPLISGFYKLLSVVMKNAKKSRYFEGFTSKIYKKAPEDPERLSCFALFAKFGKEVSSKIRQFKDELLASCLTFVLHLPHDIIMMDIKAYIPALQTAFKLGLSCPPLADVGLNALQYWSTNIPSDILKPYYKDIIPLLDGYLTNLSSTNESLSTLDMVRISRSLHKGFNKQLIQQLKRMKTLSVKEESSLTAVRNRVVRILGSLGGQINRSLVTAASTEEMIKRHVSWDTEKRLRFDVPFKDLKPVIYLDMFLPHITELALSTSDRQTKVAACELLHSIVAFMLGKATQMPDDKKTGSSPMYKIYKRTFPVLLRLACDVDKVTEQLYKPLVMSLIHWFTNNKKFESQDTVALLEAILTGIVDPVDSTLRDFCGQCIQEFLRWSIKQTTPDQQAKSPVNTTSLFKRLYSLALHPNAFKRLGAALAFNNIYRDFREETALVENFVFEVLVIYMESLALSHADEKSLGTTQQCSDAVDHLKRIIIRKAASLNKATKRRIPRGFPQGNTVCLFDIVLWLLEQCGRPQTECRHKAMQLFFEFVPLLPGNKPLTAWLDDQVEKEGIIFLINRFEGAGHSDGMHTGIFNIPALHDLHEPFSMHAVLQWLDMLLAALDCYNTFIGMRFLKANTVLGKNAEKSSFLKAAFFFITSLSMENIKAAEQCMGSKSSVFSPHEIEAYNYSKCTIIVRIMEFITMFIDICQQDSLKILENSVFNEPMWELIAITVCDPSSIGFNTADVEVINNLPNICIKLMKALGNTSYRSSLEVSLKKRVTLQSIEELCSVDLYDPGARFNRVKLGSVLSACKQLYKAEFFNSIVPEQVGGQRFGSKLLSVVYKGIAPTNERKSLPSLDISSKRLAEGLLELAFMFGGQCEELVSLLLNTVILSVPLPGTSQRNIINFSHGGYFYTLFAETINTELLNNLDTIVVELMKSSLEDPKMVSCVLNGMLDQSFRQRTIRKQQGVKLVNAVLENWRRLDSWWYKDSPSESKMAVLTLLAKVLQIDSSVCFDINHSAFAEVFKTYTSILTDQKLGLNLKSQAIIILPFFTKLTGEKLTELKNTLDQFVASNFPMKSDEFPKGTLKFNNYVDCIKKFLDALELSQSPMLLQLMTEILCRDERHFMEELFQSSFKKVIKRSSCDTQVILLNTLHNMFKSESLMLNGTLQSLIDRCLLTLLWNCSLDAMISFFTNIISLAMDTLKSRFTKVPEAAFDSQITKKWGYYKMLEVQYSRLSKDEIYSTVNNAYHVSSKPEGNELTKALIKLCYDTFTENMCGETQLLEKRRQYHCAAYNCAISLISCVFSELKFYQGFLFTEKKEKNLLIFENLIDLQRNYTFPIEVEVPMERKKKYFAIRKEARDASSTESDEPSYLSSQSYMADSSLIEEMSQFDFSTGVQSFSYSSQSKMLSQSASRKKEQITEGKTFDDVMEFEMDELNQHECMAAMTGLIKHMNRSEITPKVDEDASPQELPSWMKFLHVKLGNTSTPLNIRLFIAKLIVNTEEVFRPYARFWIGPILQLIVSGNNGGTGIHYMVVETLVTILSWSSIATPNGQAKEEILANRLLEFLMKNVFHEKRAVFRHNLEIIKTVLECWKECLSIPYRLIYEGFSGTDPNTKDNSVGIQLLGLALANNFSPLDPKCGIDPERYFQSLANNLGLTRFKEVYIAAAEVIGLVLRYIVQNEKRTEAPVFDYVVKELKRHQTNNKEDKFIMCLNKVVKNFPPFADRFMTIVLFLLPKLHGVLKTQCLEIIMHRAEDIPDLFIELKNKDFCQIMNNRDDERQRVCLDIIYKILSKLTPAELHEFLIPVTAFSSHSFPVCRERMYDIFMWIYDNYRDHESQNDSKSVEVFNMAKEGLLQGLVDENTELQLIVRNFWSDETRLPSNTTERMLAILSSLYSPKIEKHYLSLATNLLLEMTSKSPDYIRKMFEHPLSECKFQDYTVDSSWRFRSSVLTPMFVETQLSQSMQRSRAQGTIEADEPIGGQLRATQQHYQFTPTQNIGGRSSFNWLTGSSMDTLADYSVESPESLPSALLFVNKRNENVRRVPLKPLGPNFGMRRLGLPGDVTDSKTKSMEDRSDILRLRRRFLKDREKLSLIYARKGTAEQKREKAIKIEQKMKQDAQITLYRNYRQGELPDIQISYSNLIAPLQALAQRDPTMAKLLFSSLFSGILTDTASDISVTDKLLKQFNSFLSNSLSYFPPFIACVQDMCYQHDELLHLNPANISTSCLASLQQPLGILLLEKGLLHMKVPDEPPAKKMRKEKEKAEIPPDIVRWIELAKLYRSIGDYDVLRGIFSGKIGAKSITQCALNAEAKSDYAKAAKLYDEALTETFSDGDPTDAEKDFWELASLECYNHLTEWKPLEYCSTVNIDTGKPPDLNKMWSDPFYQETYLPYMIRSKLKMLLGGNNDQTLLTFVDEAMKVEQRKVLMETFYSQELSLLYILQDDFDRAKYYINNGIQVFMQNYSSIDCLLYQSRLTKLQSVQALTETQDFISFIRKPGNVSSSSLRKLFQGWMKRYPDSKMDPMNIWDDIISNRCFFLDKIQDVAVGHPQLVDESMEVDDLADGNEAMEVDRQEDIAVMINKCRFTMKMKMVDSARKQNNFSVAMKLLKDLHRESKTNEDWSVKWIHSYSRYSHSRSRDLTCSEQILTALKTIPLLEESKTEYLTKNTKACRYQNMLLGDTYRIMADAVCKEPDCLYKIEDGKAGKVKDLSESPENVVGGLYRKSLHYFTNAVRKATEEEQSHSTDQIDVRGIIKAYMTLVDFCDSHLRKVEEESAVMDRADYQNFPEIMVEKMIKALKLNSSEARLKFPRMLQIIEQYPSETLDLMARENCTVPCWQFIGWISQMMAMLDKKESIAVQHIIEEIAENYPQALVYPFMVSGESYNFEDTVVGHKNREYVNRIKSKLDKDNVAQDFIRALEQLSNPPMIFQDWWEDVSNELSKPNVNKNKIKELYKEMYTNLGNPKDHFMGAFRRRFCEKYTKDFDKAFGPEGSKLLNIKCDGFNKTVGPLITKMKEQQKEPGNLKEYSPWMSEFKPEFLRNELEIPGQYSGRSKPMPEYHVKISGFDERVSVMASIRKPKRIIVRGNDEREYPFLVKGGEDLRQDQRIEQLFEIMNIILSQDAACSQRHMQLKTYQVIPMTTRIGLIEWLENTCTLKEFILNTMTEDEAKIYNSKTTNGPLYHYNAWLDKKEKVGDARQHVTSYTRCDRTNTVASFREREALVPKDLLRRAFVKMSTTPEAFLSLRSHFARSHALLCVSHWIVGIGDRHLSNFMINMETGGMIGIDFGHAFGTATQFLPVPELMPFRLTRQIVNLMLPMKDSGLFDSVMVHSLRAYRSDPGLLVTTMDVFIKEPSLDWKNLELKQMKKKGEWKKAVDVTSHNWHPQQKIHCAKRKLDGANPCEITCEELRLGHESAPEYKDFIAVARGDKKHNRRTNEPPDGLTEETQVQCLIDQATDPNILGRVWKGWEPWI

PRKDC

DNA-dependent protein kinase catalytic subunit

4144 amino acids

Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (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 (By similarity). 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).

Belongs to the PI3/PI4-kinase family.

473.061 kDa

MFSSSQIPRVFLIPSRRELRLVLQLQESLSAGDRCSAAMASYQLTRGLGQECVLSSDPAVLALQTSLVFSKDFGLLVFVRKSLSIDEFRDCREEVLKFLYIFLEKIGQKITPYSLDIKTTCTSVYTKDKAAKCKIPALDLLIKLLQTLRSSRLMDEFSIGELFNKFYGELALKTKIQDTVLEKIYELLGVLAEVHPSEMINNSEKLFRAFLGELKIQMTSAIREPKLPVLAGCLKGLSSLMCNFTKSMEEDPQTSREIFDFALKAIRPQIDLKRYAVPLAGLCLFTLHASQFSTCLLDNYVSLFEVLSKWCSHTNVEMKKAAHSALESFLKQVSFMVAKDAEMHKSKLQYFMEQFYGIIRNMDSNSKDLSIAIRGYGLFAGPCKVINAKDVDFMYIELIQRCKQLFLTQIDTVDDHVYHMPSFLQSIASVLLYLDRVPEVYTPVLEHLMVAQIDSFPQYSPKMQSVCCKALVKVFLALGGKGPVLWNCISTVVHQGLIRICSKPVILQKGVESEPEEYRASGEVRTGKWKVPTYKDYLDLFRSLLSCDQMMDSLLADEAFLFVNSSLQNLNRLLYDEFVKSVLKIIEKLDLTLEKRNVGEHEDENEATGVWVIPTSDPAANLHPAKPKDFSAFINLVEFCRDILPEKHIEFFEPWVYSFAYELILQSTRLPLISGFYKLLSVAVRNAKKIKYFEGVGMKSQTQAPKDPEKYSCFALFAKFGKEVTVKMKQYKDELLASCLTFILSLPHDIIELDIRAYIPALQMAFKLGLSYTPLAEVGLNALEEWSVCICKHIIQPHYKDILPSLDGYLKTSALSDETKNSWEVSAPSQAAQKGFNQVVLKHLKKTKNISSNEALSLEEIRIRVVQMLGFLGGQINKNLLTATSSDEMMKKCVAWDREKRLSFAVPFIEMKPVIYLDVFLPRVTELALSASDRQTKVAACELLHSMVMFTLGKATQMPECGQGFPPMYQLYKRTFPALLRLACDVDQVTRQLYEPLVMQLIHWFTNNKKFESQDTVALLETILDGIVDPVDSTLRDFCGRCIREFLKWSIKQTTPQQQEKSPVNTKSLFKRLYSFALHPNAFKRLGASLAFNNIYREFREEESLVEQFVFEALVTYLESLALAHTDEKPLGTIRQCCDAIDHLRHIIEKKHVSLNKVKKRRRPRGFPPSASLCLLDMVQWLLAHCGRPQTECRHKSIELFYKFVPLLPGNKSPSLWLKDILKNKDTSFLINTFEGGGGSCDRPSGILVQPTLFHLQGPFSLRAALQWMDMLLAALECYNTFIEEKTLKAPDVLGTETQSSLWKAVAFFLDNIAMHDITAAEKCFGTGAAGHRPSPQEGERYNYSKCTIVVRIMEFTTTLLNTSPDGWKLLEEDLCNNKNFMTLLVKILCQPSSIGFNIGDVLVMNHLPDVCVNLMKALKKSPYKDTLEMCLKEKITVQSIEELCAVDLYGPDAYVDRATLASVVSACKQLHRAGVLHVVLPSQSADQRHSVGIKLLFLVYKSIAPGDEREYFPSLDPSCKRLASGLLELAFAFGGLCEHLVDLLLDTAVLSMPASGESQRNMVSFSHGEYFYSLFSEIINTELLRNLDMTVLKLMKSSVDNPKMVSAILNGMLDQSFRDRASRKQQGLKLASTILHNWKKWDSWWAKDSAPESKTAVLTLLAKILQIDSSVSFNTNHSAFPEVFTTYTSLLADSNLGLHLMGQAVILLPFFTNLTGGNLEDLEHVLEKLIVSNFPMKSEEFPVGTLRYSNYVDCMKKFLDALELSQSPVLLQLMAEILCREQQHVMEELFQSTFKKIARKSSCVTQLALLESVYRMFKRDDLLSNVTRQAFVDRSLLTLLWHCGLNALREFFGKIVVETIDVLKSRFTKLNESTFDTQITKKMGFYKMLDVMYSRLSKDDVHSKESKINQVFHGSCITEGNELTKTLIKLCYDAFTENMAGENQLLERRRLYHCAAYNCAISVICCVFTELKFYQGFLFSEKPEKNLLILENLIDLKRCYTFPIEVEVPMERRKKYIEIRKEAREAVNGDSDGPHYLSSLSYLADSSLSEEMSQFDFSTGVQSYSYGSQDPKSTHGHFRRREHKDPMVQDAVLELEMDELNQHECMATMTALIKHMQRNQILSKDEGSVPRNLPPWMKFLHDKLGNPSVSLNIRLFLAKLVINTEEVFRPYAKYWLSPLLQLVVSENNGGEGIHYMVVEIVVTVLSWTGLATPVGVPKDEVLANRLLHFLMEHVFHQKRAVFRHNLEIIKTLVECWKDCLSVPYRLIFEKFSSKDPNSKDNSVGIQLLGIVMANNLPPYDPKCGIERIKYFEALVSNMSFVKYKEVYAAAAEVLGLTLRYITERENILENVVYELVIKQLKQHQNTMEDKFIVCLNKVVKNFPPLADRFMNAVFFLLPKFHGVMKTLCLEVVLCRAEEITNIYLELKSKDFIQVMRHRDDERQKVCLDIIYKMMAKLKPVELRDLLNSVVEFISHPSPVCREQMYNILMWIHDNYRDPESQADDDSREVFKLAKDVLIQGLIDENAGLQLIIRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHFLSLATDFLLEMTSLSPDYANPVFEHPLSECEFQEYTIDSDWRFRSTVLTPMFIETQASQSTLQTRTQERSLPAQGVMARQIRATQQQYDFTPTQTADGRSSFNWLTGSSIDPLVDYTVSSSDSSSSSLLFAQKRNEKSQRAPLKSVGPDFGEKKLGLPGDKVDNKAKGIDNRTEILRLRRRFIKDQEKLSLIYARKGIAEQKREKEIKSELKMKHDAQVILYRSYRQGDLPDIQIKYSSLVTPLQAVAQRDPVVAKQLFGSLFSGIIKEMDKYKTMSEKNNITQKLLQDFSHFLNSTFSFFPPFVSCIQEISCQHTDLLSLDPGSIRASCLASLQQPVGVRLLEEALLHLGPQEPPAKQFKGRMRVSPDVVRWMELAKLYRSIGEYDILRGIFSSEIGTKQITQSAIFAEARSDYSEAAKQYNEALNKEEWVDGEPTEAEKDFWELASLDCYNQLAEWKSLAYCSIVSVDNENPPDLNKMWSEPFYRETYLPYMIRSKLKLLLQGEADQSLLTFIDEAVNKDLQKALIELHYSQELSLLYILQDDIDRAKYYIENCIQIFMQNYSSIDVLLHRSRLTKLQSVQTMIEIQEFISFISRQGNLSSQAPLKRLLKSWTNRYPDARMDPVHIWDDIITNRCFFLSKIEEKLTLPLGDHSLSMDEERDSSDKMEVQEQGEEVCSLIKNCMFSMKMKMVESARKQHNFSLAMKLLKELRRESKTRDDWQVKWVHTYCRLSHSRIQGQSCLQQILSALKTVSLLAGESTSSYFSKNVLAFHDQNILLGTTYSIIANALRREPACLAEIEESRARRILDLSGSSLENAEKVIAVLYQRAFHHLSEAVRTAEEEAQPSLRGQGPVASLTDAYMTLADFCDQQLRKEEESASVTESVELQTYPGLVVDNMLKALKLHSSEARLKFPRLLQIIELYPEETLSLMTKEISSTPCWQFIGWISHMVALLDQEEAVAVQCTVEEIADNYPQAIVYPFIISSESYSFKDTSTGHKNKEFVARIKTKLDLGGVIQDFISALEQLSNPEMLFKDWTDDMKAELAKNPVSKKNIEKMYERMYAALGDLRAPGLGAFRRRFIQVFGKEFDKHFGKGGSKLPGMKLRDFGSITDSLFYKMCTDSKPPGNLKECSPWMSDFKVEFLRNELEIPGQYDGKGKPLPEYHARIAGFDERIKVMASIRKPKRIIIRGRDEKEYPLLVKGGEDLRQDQRIEQLFEVMNVLLSQDTACSQRNMQLKTYHVIPMTSRLGLIEWIENTLTLKDFLLSNMSREEKAAYTSDPKAPPCEYRDWLAKMSGKYDVGAYMSMFKAASRTETVTSFRRRESRVPADLLKRAFLKMSTGPAAFLALRSHFASSHALMCISHWILGIGDRHLNNFMVSMETGGLIGIDFGHAFGSATQFLPVPELMPFRLTRQFINLMLPMKEAGVVYSIMVHALRAFRSHSDLLTNTMDVFVKEPSFDWKNFEQKMLKKGGSWIQEINVTEKNWYPRQKIHYAKRKLAGANPAVITCDELFLGHEKALAFGDYVAVARGSKDHNIRAQQPENGLSEEAQVKCLIDQATDPNILGRTWIGWEPWM

PRKDC

DNA-dependent protein kinase catalytic subunit

4134 amino acids

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. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism (By similarity).

Belongs to the PI3/PI4-kinase family.

472.657 kDa

MAGGVQECLQELHGCLQPGDAMRGYGLLRGLGEACLTCLAGGALALHVSLVFAPERGLLAFVCRSLGVEEFRECREEALKFLCVFLERIGERAHPYACSLKQTCISVYTKERAAKCKIPALELLIKLLQSLRRSCLMEEMKVGEIFNKFYGELAVRSKISDTVLEKIYELLGVLGEVHPADMINNSEKLFRAYLGELKTQMTSATRVPKLPIVAGCLRGLTALMYNFTKSVDEDAQTSKEIFDFAVKAIRPQVDQKRYAVHLAGLQLFSWHAAQFGTLLLDSYVMLFETMCRWCGHTNQELKKAGHNALDSFLKQMSLMVAKDAELHKSKLKFFMEQFYGIIRRMDSSNKELSIAIRGYGLFAAPCKAMHPADVDAMYIELLQRCKQMYLTEAETIDDHLYQLPSFLQSIASVIFHLDTIPEVYTPVLEHLVVLQINSFPRYSEKMQLVCCRSIIKVFLALSIKGPVLWNFISTVVHQGLIRVFSKPMKFSKDVFGKETSGSEEFPESGEVDTARWKVPTYKDYLYLFRSLLSCDTMKESIFEEENFLTGNSPLQSLNRLLYDELIKSILKIIEKLDLTVQKLNVHEQDENETDSAFIGPTSDPASNLQPKKPTDFIAFINLVEFCRDILPDKHVEYFQPWVYSFGYELIIHSTRLPLISGFYKLLSVTMKIAKKIKYFEGVGPKSLRKATEDPEKSSCFALFAKFGKEVTAKMKQYKDELLASCLNFLLSLPHDIVMLDIKAYIPALQNAFKLGLSCTPMADLGLDALEDWSAHIPRHIMQPYYKDVLPLLDGYLKNSATTVEPQNNWEVRKLSRAAQKGFNKIVIQRLRKAKTSSLDDNPSLEAVRTRVARLLGSLGGQINHNLITATSAEEMMKKCVSWDTKNHLSFAVPFADMKPVIYLDVFLPRVTDLALSASDRQTKIAACELLHSIVAYMLGKASQMPERQQGPPPMHQLYKRIFPVLLRLACDVDQVTRQLYEPLVMQLIHWFTNNKKFESQDTVTFLEAILSGIVDPVDSTLRDFCGQCVREFLKWSIKQTTPKQQEKSPANTKSLFKRLYSLALHPSAFKRLGAALAFNSIYREFREENSLVEQFVFEALVVFLESLALTHTDEKSLGTTQQCCDAINHLKRIIKHKAPALNKEGKRRVPRGFPATKSVCLQDVVMWLLVQCGRPQTECRHKAMELFYEFVPLLPGNNSPSSWLADVLKKRDVSFLINKFEGGGSDAKSPSGILSQPTLRDMQEPFSLLTVMRWMDMFLAALDCYNTFFELRMIKPHEILGVNERSSFLEAVDFFLETIALHDIHAAEQCFDCRSRGNIFSPQEREVYNYSKCTIIVRIMEFVTMILEICQQDFWKLLEKELLNANFIELLVMTVCDPSHIGFNTADVQVMKNLPDISVRLLKALMKSPYKEYLQLCLKKRITPQSFEDLCSVDLFNSDARFDQVRFSAVLSACKQLQKSGLLHSVLHSQDERPHPSIGSKLLSVVYKSIAPGSERSSLPAVDISSKRLADRLLQLAFAIDDQCEELVSLLLNTVVLSVPLSKASERNFVDFSHGQYFYSLFSDTINQQLLKNLDVIVIHLMESSVSNPQMVGSILNGMLDQSFRERTIRKQQGVKLVTAVLRNWKRLDSWWAKDSSPESKMAVLTLLAKVLQIDSSVSFNTSHEAFTAVFDTYTSLLTDQNLGLNLKGHAVIILPFFTNLSGEKLHDLKNALDQLVAFNFPMSSDEFPKGTLKHNNYVDCTKKFLDALELSQSPMLLQLMTEVLCRDHRHSMEDLFQASFKRISRRSSTDKQVVLLDTVHKMFQNEDLLSNIVRQAFVDRSLLTLMSHCSLDALREFFCKIIVQAMDTLNSRFTKSNECVFDTQITKKMGYYKMLEVMYIRLSKDDVHSKDSKINQAYRGSVSVEGNELTKALIKLCYDAFTENMAGENQLLEKRRQYHCAAYNCAIAVISCVFTESKFYQGFLFTEKSEKNLLIFENLIDLKRQYVFPVEIEVPLERKKRYIAIRKEAREAWNDGQDEPKYLASASYMMDSSLSEEMSQFDFSTGVQGFSYSSQDVTASSAHFRRKETSEYMVLNDEMELEMDELNQHECMAPLTTLIKHMQRNQITPKVEEGVIPVDLPLWMKFLHSKLGNPSVPLNIRLFIAKLIVNTEDVFRPYAKQWLGPMLQLVVSGDNGGEGIHYMVVEIAVTVLSWTSVTTPKGNIKDEILANRLLEFLMKNAFHQKRAVFRHNLEIIKTVIECWKNCLSIPYSLIFEKFSSGDPDTKDNSVGIQLLGIVLANNLPPFDLKCEIDRVRYFQALVSNMGLLRYKEVYAAAAEVLGLALQYIAERQNILEDPVYDCVIKQLKRHQNTQQDKFIICLNKVVKNFPPLADRFMNAVFFLIPKLHGVMKNYCLEVIMCRAEEIPDLYLQLKSKDFIQIMKHRDDERQRVCLDIIYKMLSTLKPPELKELLPGVTGFISHPSVICRQRMYDILMWIYDNYSDPESQADGDSQEVLSLAKEILLQGLIDENAELQLIVRNFWSDETRLPANILDRMLMLLNSLYSAKIETQYLSLITNFLLEMTSKSPDYSRKIFEHPLSECKFHDFVIDSSWRYRSTMLTPMFVETQASQSTNRNSSQERSLSISGSVGGRVRATQRQYEFTPTQNVSGRSSFNWLTGNSIDTLAEYTVPSSSESLSSSMLLVNKRSEKFKQAAFKPVGPDFGKKRLSLPGDKVDSKTKGIDERAEILRLRRRFLKDQEKVSLIYARKGVAEQKREKEMKSELKMKFDGQVTLYRSYRVGDLPDIQIEHCSLIAPLQGLAQKDPTFAKQLFSSLFGGIFCEVKKSKIPSEKKAIIQKLLKDFNHFLSTSVSYFPPFIACIQEISYKHRELLELDSANVSTSCLASLQQPVGILLLEHALMALSPAEEPPSKRMRGRTELPPDVVKWLELAKLYRSLGDYDVLRGIFSGKIGTKDITQQALLAEARSDYAEAAKCYDEALSKEDWEDGEPTEAEKDFWELASLECYDHLTEWKSLEYCATVNIDSGKPPDLNKTWSDPFYQETYLPYIIRSKLKLLLNGENDQTLLTFIDEAMKTEQKKALIEMHYSQELSLLYILQDDFDRAKYYIGNGIQIFMQSYSSIDTLLYQSRMSKLQSVQALTEIQDFINFMTKTSNIASQAKSLKRLLRTWTSRYPDAKMDPMNIWDDIITNRCFFLDKLQEKFLCDKANDSMEVDEESSVGDQMEVDQQDEDIHSMIRSCKFNMKLKMIESARKQNSFSIAKKLLKGLRREAKTREDWLVRWNYAYCRFVHSCSQSQSCPERVLSVLKTISLLEDTKSDYLNKNIMAFRNQNLLLGTTYHIMANALSQDPKCCEQIEEEKTGKILELSGESSESPEKILAGLNKRAFQCFSSAARKSEEEVQSLSMEHVDVKGVIDAYMTLVGFCDQHLRKEEEGSLEINAADLQLFPAIVVEKMIKALKLNSREARLRFPRLLQIIERYPAETLGLVTRELPSVPCWQFIGWISQMMALLDKDEAVAVQHTVEEIVDTYPQAIIYPFTISSESYCFKDTAAGCRNKEFVASIKNKLDRGGVVQDFIHALEQLSNPVMLFKDWVADVRNELVKTQRNKIILKEMYEGMYKNLGDVKAPGLGWLRKRFVQAFGKDFDSHFGKGGSKLLDMKISDFNEITTALLTKMNKTHKEPGNLKECSPWMSEFRAEFLRNELEVPGQYDGKGKPLPEYHVKISGFDERIMVLESLRKPKRITIRGSDEQEHPFLVKGGEDLRQDQRIEQLFDVMNIVLSRDAACSQRNMQLKTYQVIPMTTRLGLIKWLENTCTLKEFLRNSMTEEEDANYNSLKGPRAAYSDWLSKMGGKAQGLSRYNAMYKNASRTETVIAFKSRESSVPEDLLRRAFVKMSTSPEAFLALRSHFVSSHALMCVSHWILGIGDRHLSNFMINKETGGMVGIDFGHAFGSATQFLPVPELMPFRLTRQFVNLMMPVKEWGLIYSVMVHALRAYRADPDLLISTMDVFVKEPSLDWKNFEQRQLKKGGTWIKEINTAEVNWYPLQKVSYVKRKLTGANPARITCDELRLGYEKLPFYNDFAAVARGSADHNIRAKEPEDRLSEETQVRCLIDQATDPNLLGRVWEGWEPWM

PRKDC

DNA-dependent protein kinase catalytic subunit

4128 amino acids

Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805). 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) (PubMed:11955432). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Required to protect and align broken ends of DNA (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). 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 (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Recognizes the substrate consensus sequence [ST]-Q (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:2507541, PubMed:2247066, PubMed:1597196, PubMed:8407951, PubMed:8464713, PubMed:9362500, PubMed:9139719, PubMed:10026262, PubMed:10467406, PubMed:12509254, PubMed:11889123, PubMed:14612514, PubMed:14704337, PubMed:16397295, PubMed:26237645, PubMed:28712728). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). 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 (By similarity). 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 (PubMed:28712728).

Belongs to the PI3/PI4-kinase family.

469.089 kDa

MAGSGAGVRCSLLRLQETLSAADRCGAALAGHQLIRGLGQECVLSSSPAVLALQTSLVFSRDFGLLVFVRKSLNSIEFRECREEILKFLCIFLEKMGQKIAPYSVEIKNTCTSVYTKDRAAKCKIPALDLLIKLLQTFRSSRLMDEFKIGELFSKFYGELALKKKIPDTVLEKVYELLGLLGEVHPSEMINNAENLFRAFLGELKTQMTSAVREPKLPVLAGCLKGLSSLLCNFTKSMEEDPQTSREIFNFVLKAIRPQIDLKRYAVPSAGLRLFALHASQFSTCLLDNYVSLFEVLLKWCAHTNVELKKAALSALESFLKQVSNMVAKNAEMHKNKLQYFMEQFYGIIRNVDSNNKELSIAIRGYGLFAGPCKVINAKDVDFMYVELIQRCKQMFLTQTDTGDDRVYQMPSFLQSVASVLLYLDTVPEVYTPVLEHLVVMQIDSFPQYSPKMQLVCCRAIVKVFLALAAKGPVLRNCISTVVHQGLIRICSKPVVLPKGPESESEDHRASGEVRTGKWKVPTYKDYVDLFRHLLSSDQMMDSILADEAFFSVNSSSESLNHLLYDEFVKSVLKIVEKLDLTLEIQTVGEQENGDEAPGVWMIPTSDPAANLHPAKPKDFSAFINLVEFCREILPEKQAEFFEPWVYSFSYELILQSTRLPLISGFYKLLSITVRNAKKIKYFEGVSPKSLKHSPEDPEKYSCFALFVKFGKEVAVKMKQYKDELLASCLTFLLSLPHNIIELDVRAYVPALQMAFKLGLSYTPLAEVGLNALEEWSIYIDRHVMQPYYKDILPCLDGYLKTSALSDETKNNWEVSALSRAAQKGFNKVVLKHLKKTKNLSSNEAISLEEIRIRVVQMLGSLGGQINKNLLTVTSSDEMMKSYVAWDREKRLSFAVPFREMKPVIFLDVFLPRVTELALTASDRQTKVAACELLHSMVMFMLGKATQMPEGGQGAPPMYQLYKRTFPVLLRLACDVDQVTRQLYEPLVMQLIHWFTNNKKFESQDTVALLEAILDGIVDPVDSTLRDFCGRCIREFLKWSIKQITPQQQEKSPVNTKSLFKRLYSLALHPNAFKRLGASLAFNNIYREFREEESLVEQFVFEALVIYMESLALAHADEKSLGTIQQCCDAIDHLCRIIEKKHVSLNKAKKRRLPRGFPPSASLCLLDLVKWLLAHCGRPQTECRHKSIELFYKFVPLLPGNRSPNLWLKDVLKEEGVSFLINTFEGGGCGQPSGILAQPTLLYLRGPFSLQATLCWLDLLLAALECYNTFIGERTVGALQVLGTEAQSSLLKAVAFFLESIAMHDIIAAEKCFGTGAAGNRTSPQEGERYNYSKCTVVVRIMEFTTTLLNTSPEGWKLLKKDLCNTHLMRVLVQTLCEPASIGFNIGDVQVMAHLPDVCVNLMKALKMSPYKDILETHLREKITAQSIEELCAVNLYGPDAQVDRSRLAAVVSACKQLHRAGLLHNILPSQSTDLHHSVGTELLSLVYKGIAPGDERQCLPSLDLSCKQLASGLLELAFAFGGLCERLVSLLLNPAVLSTASLGSSQGSVIHFSHGEYFYSLFSETINTELLKNLDLAVLELMQSSVDNTKMVSAVLNGMLDQSFRERANQKHQGLKLATTILQHWKKCDSWWAKDSPLETKMAVLALLAKILQIDSSVSFNTSHGSFPEVFTTYISLLADTKLDLHLKGQAVTLLPFFTSLTGGSLEELRRVLEQLIVAHFPMQSREFPPGTPRFNNYVDCMKKFLDALELSQSPMLLELMTEVLCREQQHVMEELFQSSFRRIARRGSCVTQVGLLESVYEMFRKDDPRLSFTRQSFVDRSLLTLLWHCSLDALREFFSTIVVDAIDVLKSRFTKLNESTFDTQITKKMGYYKILDVMYSRLPKDDVHAKESKINQVFHGSCITEGNELTKTLIKLCYDAFTENMAGENQLLERRRLYHCAAYNCAISVICCVFNELKFYQGFLFSEKPEKNLLIFENLIDLKRRYNFPVEVEVPMERKKKYIEIRKEAREAANGDSDGPSYMSSLSYLADSTLSEEMSQFDFSTGVQSYSYSSQDPRPATGRFRRREQRDPTVHDDVLELEMDELNRHECMAPLTALVKHMHRSLGPPQGEEDSVPRDLPSWMKFLHGKLGNPIVPLNIRLFLAKLVINTEEVFRPYAKHWLSPLLQLAASENNGGEGIHYMVVEIVATILSWTGLATPTGVPKDEVLANRLLNFLMKHVFHPKRAVFRHNLEIIKTLVECWKDCLSIPYRLIFEKFSGKDPNSKDNSVGIQLLGIVMANDLPPYDPQCGIQSSEYFQALVNNMSFVRYKEVYAAAAEVLGLILRYVMERKNILEESLCELVAKQLKQHQNTMEDKFIVCLNKVTKSFPPLADRFMNAVFFLLPKFHGVLKTLCLEVVLCRVEGMTELYFQLKSKDFVQVMRHRDDERQKVCLDIIYKMMPKLKPVELRELLNPVVEFVSHPSTTCREQMYNILMWIHDNYRDPESETDNDSQEIFKLAKDVLIQGLIDENPGLQLIIRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHFLSLATNFLLEMTSMSPDYPNPMFEHPLSECEFQEYTIDSDWRFRSTVLTPMFVETQASQGTLQTRTQEGSLSARWPVAGQIRATQQQHDFTLTQTADGRSSFDWLTGSSTDPLVDHTSPSSDSLLFAHKRSERLQRAPLKSVGPDFGKKRLGLPGDEVDNKVKGAAGRTDLLRLRRRFMRDQEKLSLMYARKGVAEQKREKEIKSELKMKQDAQVVLYRSYRHGDLPDIQIKHSSLITPLQAVAQRDPIIAKQLFSSLFSGILKEMDKFKTLSEKNNITQKLLQDFNRFLNTTFSFFPPFVSCIQDISCQHAALLSLDPAAVSAGCLASLQQPVGIRLLEEALLRLLPAELPAKRVRGKARLPPDVLRWVELAKLYRSIGEYDVLRGIFTSEIGTKQITQSALLAEARSDYSEAAKQYDEALNKQDWVDGEPTEAEKDFWELASLDCYNHLAEWKSLEYCSTASIDSENPPDLNKIWSEPFYQETYLPYMIRSKLKLLLQGEADQSLLTFIDKAMHGELQKAILELHYSQELSLLYLLQDDVDRAKYYIQNGIQSFMQNYSSIDVLLHQSRLTKLQSVQALTEIQEFISFISKQGNLSSQVPLKRLLNTWTNRYPDAKMDPMNIWDDIITNRCFFLSKIEEKLTPLPEDNSMNVDQDGDPSDRMEVQEQEEDISSLIRSCKFSMKMKMIDSARKQNNFSLAMKLLKELHKESKTRDDWLVSWVQSYCRLSHCRSRSQGCSEQVLTVLKTVSLLDENNVSSYLSKNILAFRDQNILLGTTYRIIANALSSEPACLAEIEEDKARRILELSGSSSEDSEKVIAGLYQRAFQHLSEAVQAAEEEAQPPSWSCGPAAGVIDAYMTLADFCDQQLRKEEENASVIDSAELQAYPALVVEKMLKALKLNSNEARLKFPRLLQIIERYPEETLSLMTKEISSVPCWQFISWISHMVALLDKDQAVAVQHSVEEITDNYPQAIVYPFIISSESYSFKDTSTGHKNKEFVARIKSKLDQGGVIQDFINALDQLSNPELLFKDWSNDVRAELAKTPVNKKNIEKMYERMYAALGDPKAPGLGAFRRKFIQTFGKEFDKHFGKGGSKLLRMKLSDFNDITNMLLLKMNKDSKPPGNLKECSPWMSDFKVEFLRNELEIPGQYDGRGKPLPEYHVRIAGFDERVTVMASLRRPKRIIIRGHDEREHPFLVKGGEDLRQDQRVEQLFQVMNGILAQDSACSQRALQLRTYSVVPMTSRLGLIEWLENTVTLKDLLLNTMSQEEKAAYLSDPRAPPCEYKDWLTKMSGKHDVGAYMLMYKGANRTETVTSFRKRESKVPADLLKRAFVRMSTSPEAFLALRSHFASSHALICISHWILGIGDRHLNNFMVAMETGGVIGIDFGHAFGSATQFLPVPELMPFRLTRQFINLMLPMKETGLMYSIMVHALRAFRSDPGLLTNTMDVFVKEPSFDWKNFEQKMLKKGGSWIQEINVAEKNWYPRQKICYAKRKLAGANPAVITCDELLLGHEKAPAFRDYVAVARGSKDHNIRAQEPESGLSEETQVKCLMDQATDPNILGRTWEGWEPWM

Prkdc

DNA-dependent protein kinase catalytic subunit

4128 amino acids

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). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (By similarity). Required to protect and align broken ends of DNA (By similarity). May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (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). Recognizes the substrate consensus sequence [ST]-Q (By similarity). Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism (By similarity). Phosphorylates DCLRE1C, C1D, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, 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). 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).

Belongs to the PI3/PI4-kinase family.

471.471 kDa

MAEEGTGVRCWLLQLQEFLSAADRCSAAGASYQLIRSLGQECVLSTSSAVQALQISLVFSRDFGLLVFIRKSLSIEDFRDCREEALKFLCVFLEKIDQKVMHYSLDIKNTCTSVYTKDRTAKCKIPALDLLIKLLQILRSTRLMDEFKIGELFNKFYGELASKSKLPDTVLEKVYELLGVLGEVHPSEMINHSENLFRAFLGELKTQMTSTVREPKFPVLAGCLKGLSSLLCNFTKSMEEDPQTSKEIFGFTFKAIRPQIEMKRYAVPLAGLRLLTLHASQFTACLLDNYITLFEVLSKWCSHTNVELKKAAHSALESFLRQISFTVAEDAELHKSRLKYFMEQFYGIIRNTDSNNKELAIAIRGYGLFAGPCKVINAKDVDFMYVELIQRCKQMFLTHADASEDHVYQMPSFLQSIASVLLYLDTVPEVYTPVLEHLMVVQIDSFPQYSPKMQLVCCKAIIKLFLALSEKGPVHWNCISAVVHQGLIRICSKPVVLQKDVESRSDNRSASEEVRTGRWKVPTYKDYVDLFQHLLGCDQMEDFILGDETFLFVNSSLKSLNHLLYDEFIRSVLKIVEKLDLTLEKQTVGEQEDGSTADVWVIPTSDPAANLHPAKPSDFSALINLVEFCREILPRKHVGFFEPWVYSFAYELILQSTRLPLISGFYKLLSIAVKNARKIKYFEGISPKSLKHSPEDTEKYSCFALFAKFGKEVSVKMKQYKDELLASCLTFVLSLPHDIIELDVRAYVPALQMAFKLGLSHMPLAEIGLHALKEWSVHIDKSILQPYYKDILPCLDGYLNTSTLSDETKSHWGLSALSRAAQKGFNRHVVKHLKRTRNSSPDEALSLEEIRIKVVQILGSLGGQINKSLVTATSGERMKKYVAWDAERRLSFAVPFREMKPVIYLDVFLPRVTELALSASDRQTKVAACELLHSMVMFMLGRATQMPEGQGLPPMYQLYKHTFPVLLQLACDVDQVTRQLYEPLVMQLIHWLTNNKKFESQDTVALLEAILDGIVDPVDSTLRDFCGRCVQEFLKWSIKQTTPQQQEKSPVNSKSLFKRLYSLALHPNAFKRLGAALAFNHIYKEFREEGSLVEQFVFEALVTYMESLALAHEDEKSLGTVQQCCDAIDHLRRIIEKKHVSLNKAKKRRLPQGFPPLTSLCLLDLVEWLLAHCGRPQTECRHKSMELFYKFVPLLPGNKSPSLWLKDLIKKKGISFLINTFEGGASSSDQPAGILAQPTLVYLQGPISLRGVLQWLDLLLAALECYNTFIEKETVQGQEVLGAEVQSSLLKSVAFFLESIATHSARAVEQRFGSGAPGPPSLHEEEKYNYSKCTVLVRIMEFTTTLLIASPEDCKLLEKDLCNTNLMQVLVKMICEPMSLGFNIGDVQVMNHLPSICVNLLKALRKSPYRDMLETHLKEKVTVQSVEELCSINLCSSGARQERSKLLSILSACKQLHKAGFSHVISPSQSTALNHSVGMRLLSLVYKGIVPAEERQCLQSLDPSCKSLANGLLELAFGFGGLCDHLVSLLLNSAMLSTQYLGSSQRNISFSHGEYFYSLFSEVINSELLKNLDIAVSRLMESSSDNPKMVSTVLNGMLDTSFRDRAVQKHQGLKLATAILQNWRKCDSWWAPDSAPESKTTVLSLLAKMLQIDSALSFDTNHSSFSEIFTTYASLLADTKLGLHLKGQAIILLPFFTSLREGSLENLKHILEKLIVCNFPMKSDEFPPDSLKYNNYVDCMKKFLDALELSQSPMLFQLMTDILCREQRHIMEELFQTTFKRIARQSPCVTQLNLLESVYTMFRKADLPSNVTRQAFVDRSLLTLLWHCDLDTLKEFFSRIVVDAIDVLKSRFTKLNEFTFDTQITKKMCYYKMLAVMYSRLLKDDVHSKEAKINQAFHGSRVAEGNELTKTLLKLCHDAFTENMVGESQLLEKRRLYHCAAYNCAISLISCVFNELKFYQGFLFNEKPEKNLFIFENLIDLKRCYTFPIEVEVPMERKKKYIEIRKEARDAANGASGSPHYMSSLSYLTDSSLSEEMSQFDFSTGVQSYSYSSQDRKPTTGHFQRREHQDSMTQDDIMELEMDELNQHECMAPMIALIKHMQRNVIAPKGEEGSIPKDLPPWMKFLHDKLGNASVSLNIRLFLAKLVINTEEVFRPYAKHWLSPLLQLAVCENNREGIHYMMVEIVATILSWTGLATPTGVPKDEVLANRLLRFLMKHVFHPKRAVFRHNLEIIKTLVECWKECLSIPYRLIFEKFSHKDPNSKDNSVGIQLLGIVIANNLPPYDPNCDITSAMYFEALVNNMSFVKYKEVYAAAAEVLGLILQYITERKHVIAELVCELVIKQLKQHQNTMEDKFIVCLNKIAKGFPPLADRFLNALFFLLPKFHGVMKTLCLEVVLCRAEEITGLYLQLKSKDFLQVMRHRDDERQKVCLDIVYKMVAKLKPIELRELLNPVVEFVSHPSPTCREQMYNILMWIHDNYRDQESQNDEDSQEIFKLAKDVLIQGLIDENVGLQLIIRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHFLSLATNFLLEMTRMSPDYLNPIFEHPLSECEFQEYTIDPDWRFRSTVLTPMFIETQASPSILHTQTQEGPLSDQRQKPGQVRATQQQYDFTPTQASVERSSFDWLTGSSIDLLADHTVFSSETLSSSLLFSHKRTEKSQRMSCKSVGPDFGTKKLGLPDDEVDNQVKSGTPSQADILRLRRRFLKDREKLSLLYAKRGLMEQKLEKDIKSEFKMKQDAQVVLYRSYRHGDLPDIQIQHSGLITPLQAVAQKDPIIAKQLFSSLFSGILKEMNKFKTTSEKNIITQNLLQDFNRFLNTTFLFFPPFVSCIQEISCQHPDFLTLDPASVRVGCLASLQQPGGIRLLEEALLRLMPKEPPTKRVRGKTCLPPDVLRWMELAKLYRSIGEYDVLRGIFSSELGTTQDTQNALLAEARSDYCQAAKLYDEALNKLEWVDGEPTEAEKEFWELASLDCYNNLSKWKELEYCSTVNIVSENSLDLSKMWSEPFYQETYLPYVIRSKLKLLLQGEGNQSLLTFVDEAMNKELQKTVLELQYSQELSLLYILQDDIDRATYYIKNGIQIFMQNYSSIDVLLYRSRLAKLQSVQTLAEIEEFLSFICKHGDLSSLGPLRRLLKTWTSRYPDVVTDPMHIWDDIITNRCFFLSKIEERLTAPSGDHSMSVDEDEESIDREVYEPKEDVRCMLQSCRFTMKMKMIESAWKQSNFSLSMKLLKEMHKESKTREIWRVQWLHSYSQLNHCRSHTQSPREQVLNMLKTITLLDESDISNYLNKNIQASCDQSILLGTTCRIMADALSREPACLSDLEENKVNSILTLSGSNAENTETVITGLYQRAFHHLSKAVQSAEEETQLSCWGHEAAAERAHAYMTLVGFCDQQLRKVEESASQKTSAEMEAYPALVVEKMLRALKLNSSEARLKFPRLLQIIEQYSEETLNIMTKEISSIPCWQFIGWISHMMALLDKEEAIAVQHTVEEIADNYPQAIIYPFIISSESYSFKNTSSGHNNKAFVERIKSKLDHGEVIHSFINALDQLSNPDLLFKDWVSDTKDELGKNPVNKKNIEKLYERMYAALGDLRAPGLGPFRRRFIQAFGKEFVKSFGNGGSKLLTMKVDDFCKITGSLLVRMKKDSKLPGNLKEYSPWMSEFKAQFLKNELEIPGQYDGKSKPLPEYHVRISGFDERVKVMLSLRKPKRIVIRGHDEKEYPFLVKGGEDLRQDQRIEQIFEVMNAILSQDAACSQRNMQLRTYRVVPMTSRLGLIEWIENTMTLKDLLLSNMSQEEKVANNSDPKAPIRDYKDWLMKVSGKSDAGAYVLMYSRANRTETVVAFRRRESQVPPDLLKRAFVKMSTSPEAFLALRSHFASSHALLCISHWLLGIGDRHLNNFMVAMETGSVIGIDFGHAFGSATQFLPVPELMPFRLTRQFVSLMLPMKETGLMCTVMVHALRAFRSCAGLLTDTMEIFVKEPSFDWKSFEQTMLRKGGSWIQEINVTEKNWYPQHKIRYAKRKLAGANPAVITCDELYLGHEASSAFRSYTAVARGNRDYNIRAQEPESGLSEETQVKCLVDQATDPNILGRTWEGWEPWM