PRKDC_DICDI
ID PRKDC_DICDI Reviewed; 4299 AA.
AC Q54UC0;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 113.
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;
GN Name=dnapkcs; ORFNames=DDB_G0281167;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=16596165; DOI=10.1371/journal.pgen.0020038;
RA Goldberg J.M., Manning G., Liu A., Fey P., Pilcher K.E., Xu Y., Smith J.L.;
RT "The dictyostelium kinome -- analysis of the protein kinases from a simple
RT model organism.";
RL PLoS Genet. 2:E38-E38(2006).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16243037; DOI=10.1016/j.cub.2005.09.039;
RA Hudson J.J.R., Hsu D.-W., Guo K., Zhukovskaya N., Liu P.-H., Williams J.G.,
RA Pears C.J., Lakin N.D.;
RT "DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum.";
RL Curr. Biol. 15:1880-1885(2005).
CC -!- FUNCTION: Serine/threonine-protein kinase that acts as a molecular
CC sensor for DNA damage. Is recruited to DNA ends by the Ku70/Ku80
CC heterodimer and is involved in DNA non-homologous end joining (NHEJ)
CC required for double-strand break (DSB) repair and V(D)J recombination
CC (By similarity). This activity is only apparent when DNA damage is
CC administered in G1 phase of the cell cycle. Required for efficient
CC signaling of DNA double-stranded breaks via phosphorylation of H2AX
CC during G1. {ECO:0000250, ECO:0000269|PubMed:16243037}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Inhibited by wortmannin. Activity of the enzyme
CC seems to be attenuated by autophosphorylation (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P78527}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:P78527}.
CC -!- PTM: May be phosphorylated upon DNA damage. Could be
CC autophosphorylated. 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). {ECO:0000250}.
CC -!- PTM: Autophosphorylated on Ser-2789, Thr-2814 and Thr-2822. Ser-2789 is
CC a DNA damage-inducible phosphorylation site (inducible with ionizing
CC radiation, IR) (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Null cells of hatched spores in G1 phase of the
CC cell cycle exhibit a marked increase in sensitivity to bleomycin when
CC compared to parental controls. Consistent with a lack of sensitivity of
CC vegetative null cells to bleomycin H2AX phosphorylation is still
CC apparent in these cells after administration of this agent during
CC vegetative cell growth. {ECO:0000269|PubMed:16243037}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. DNAPK subfamily.
CC {ECO:0000305}.
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DR EMBL; AAFI02000040; EAL66880.2; -; Genomic_DNA.
DR RefSeq; XP_640856.2; XM_635764.2.
DR SMR; Q54UC0; -.
DR STRING; 44689.DDB0229336; -.
DR PaxDb; Q54UC0; -.
DR PRIDE; Q54UC0; -.
DR EnsemblProtists; EAL66880; EAL66880; DDB_G0281167.
DR GeneID; 8622912; -.
DR KEGG; ddi:DDB_G0281167; -.
DR dictyBase; DDB_G0281167; dnapkcs.
DR eggNOG; KOG0891; Eukaryota.
DR HOGENOM; CLU_224534_0_0_1; -.
DR InParanoid; Q54UC0; -.
DR OMA; GIQIFMQ; -.
DR PhylomeDB; Q54UC0; -.
DR Reactome; R-DDI-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-DDI-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR PRO; PR:Q54UC0; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004677; F:DNA-dependent protein kinase activity; IEA:InterPro.
DR GO; GO:0004672; F:protein kinase activity; ISS:dictyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:dictyBase.
DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:dictyBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0072718; P:response to cisplatin; IGI:dictyBase.
DR GO; GO:0042770; P:signal transduction in response to DNA damage; IMP:dictyBase.
DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
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; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 3: Inferred from homology;
KW ATP-binding; Coiled coil; DNA damage; DNA repair; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..4299
FT /note="DNA-dependent protein kinase catalytic subunit"
FT /id="PRO_0000376002"
FT DOMAIN 3031..3707
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 3887..4226
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 4267..4299
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 557..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 613..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 878..917
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1206..1230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2832..2881
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3535..3559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3893..3899
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 4092..4100
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 4112..4137
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT COILED 551..590
FT /evidence="ECO:0000255"
FT COMPBIAS 558..577
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2832..2871
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2789
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 2814
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 2822
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
SQ SEQUENCE 4299 AA; 494476 MW; DC3B8FF774FE856C CRC64;
MDNIYQRIEN YLIKLFQTIS ETNNNNNNNN TNNNVGIKFE NDLLLVNELG SIILKELVLE
EEIGLVASLL FTGDHSLLKY LEKSSTISNK ENVKIKVSIL NLIAEFIEIL QVRTDDYAIA
IKNTCVLVFR KDQSHSVQAA AFGPIKKILH LMSRVLKQGS IVAESFGVSE MTQLFLLQFT
CGKLTQTVRG EIIVVLGLFT EYFSSNMCDR NQQLSFIFME TLGGQLRSKS PESTLIQSCL
KGLNSLLVHF SGDFIASDPK NVQLIYQYVY ICLDPASSTQ RFEIPRAAMK IVARHAVLLR
QYLAEHSQPF YTRIEHWCNH INKLNRDIAF TAVDSFFQQI SKELTSGNRS LEADQSTFKF
FIRKFYSIFE NNNSSRFELS IAIRGCGRFA SPVKSFMGEW ELKSLLNSLF KFSEKLMVVK
IENIDEITLH LSSFINAFAC ILYELNELEF WYLDHIEQVL ETYFIIFPHL FVKSRDRYFK
AVNRLISSLF YHGEYLKILL SRFVKKGLLI TFSKPNDSIK NLITTANTPF YQVYKDLWYN
LLNPTIDTID KDLNSTIKKE NNNNNNNKNK NNNNNQTLTK EEISKSIKKL VYDEIVSSIL
SIIKKLDLQY QKDENDNNSN SNSNNNNNND QDNNKISIIE YESEINQLKP VTSKDIELFL
GLVEFFKLFI SKYNTELFVQ WIYIFGKEMI SFSKKYPLIS GFYKLVQIVM QICKSQKYFN
ELQQDDNINS VIFNNQIIDE QLQQQQDIMD IDDTDNNSNS NNKINKKLTN SLEEDKNNCF
ILFKKYIKEV SNFISHYKDE LLSSCIELLL SLPKQLISIP LLVPIANLAF QYGISYLPLA
HVGLNAIEYW NLVVPDQVHK HLDQLLPSLN DYLKISTNSS DSTSGGDIDI DSGGSMGGGG
VVPPPSSSSR HRKMKFKSNS SLIDPKQLQF KTSIEDLQNR IIRLLGQLGG DNVHFLGKVS
LVGEEIVNGV AWDTEPKVLI KIPFADQNNI DIYLDVILPN VVNLAEKSPN RQIKVAAGEL
LHSVLLMMIG NSANQSQANQ ISYSRLYRKI FPSLICLSTD VEQVTKQLFQ PLVFQMIHWF
TRNKKQESDD TMNLLNAIVD AVGNPLDGAR RDFAGQCLCE FAKWSLKNTS VKQQEKNAFN
FKSILKRIYS LAHHPDPYKR LGAAISFNQL YRIFREEDSL VDQFIFEILH NIFFSLRIGD
DLTNTSSSKN NSNSNSNNNN NNNNNSEDGT EDSIVEIASK YSNVLAALTK VIIKRADMLN
KPSNTRREHK DLSQFVQWVF QNGCSRTESI VRYESMILFT QLVTLLPNIK TPLQWVKERI
KSNGIQFIVS IAEQQGGGVG GGSSNGNTSL GRIPKIEIGK HKDIEFWFRN LSTSLNIYLW
FFSEGFFEPI QILTSREFKS SLLSSAFHTF TTQFSMLNFN SNLKTNQQQQ QQQVSMFSSM
TPKEIDQFNR LKCNVITNLF GLYILLLEKY KFEQVIDYGG VAFVQLLVKC LMDPQSVGFV
NNYLEEREVE LSKSSRQDIR NLMSRTFKFP PLLEIINNII KLLIQIKPKY NDILHKELME
YILPNNSNNN NNSSSSGNNK SMFSLIDIRQ LINTEGTDRL IHLIHSYQIL YKYNLLDSIL
LENYNEQSEQ GIQDLPKSSL EFSEFIFDYL FNNCENLSPS KLLISKELIQ LALTIGIKPI
KLLSLIINPN VQNTTTTTTT TSTTTTTTTT TTSTNNNNDN NNEFIKDIHD IFYKTLFTEI
NNYISNNFQL FLPLLANRII ETNQIHKVLN DVCIMKQQQQ PNRGFKDIIE SIVLFLNSIS
EWTLNSNLKL VEKENIIEFT KNLIKIDPIQ FFENKHCYEF VYNIITNYLC RSNPLTFKNK
VLVLLPYLLS YPKHNNFDLI KQKLNEIVVY DFPLNSKDLT VKSPIYNEYI TCIERLLETF
ELTKNPLVID TLLHVLKETD HTHINYINLS IERSILSTND IEAKEIFSHC FELFLNHYDE
LKITLIDKFC VPLISHMKEN ILVQIFSQHL SSLMSIIQPL QPKYLSDSQE RKSSIIEKIC
CFHLIEALYQ SLPSAIIKEK INPFFYDKPD GKGTELTAAI MKAAHSAKSE KLTSDDKYVT
RSLCTKYHGA AFSALASVIV STQTKENFFH VFFFKENKDK NEYLWENIID TDQVFNFQPE
TNFLVSYSTP QSLFANDLRY LSSQYLVDSS LSQDFIAKNF LEGDNNSTTN NNNGDDGIIM
QGQSQSGDNE NQISNDIEID QVNSNPSMIA MLKIIDFYQK KFVVTPPSSI LFGQQSQQPK
PTVGDMPKWM FEIYQKLQQG VHPNIVIFMI KIIINRPQYF ERFHELWIPI LMDYVVSEGN
GGNGLHYFVR DVCFILLKWP NIYKSQDGGG GTTLEKHLSK FVNHLMKNTY CTDRRILKSN
LNIVKSFVER WKSLFKVDKS IILELLSTKG DFKSKSRQIK TTGLVLLSIL LSNGYPAYDK
EYDSNTISEF KFYQVLLDHL QDFKELYDAA SEVCGMILLY LSKQQQSQQQ QQQSIFPQLL
KDKINSILNN NENQRAFSCL YFIGLHYPLF LQGFYGKIFN LLPQISNETR LIALNIIHWC
VEDIQDLYTK LKSNNIENLI RIREGEIQVV ILRILYKLVQ KRDTTFGTVN QILSLLLSNN
WFTSNVTNEY SRSLYYDIII YIYNNFIEYQ DQSNENSKDL VLSLLIGLSD ESDSINKKLL
QFWDNNSKTL SASSNQRLQQ FFDIMYSPET ESKWVANSCC LLFQLCNRSS DFTKLLFDKP
LSECTFKEVQ VDSSWQHRTL NMNPLFSSSQ YGIDDATTDE SNGDSMQLDE IRATQAPNFT
LTQTAFSEFY PSSSQSYGGT NNNTGSSQLS SSSSSSGSQS SSQNNSSSKR KQKITNDPKL
INNSELRRRF KKIDDRGADE RIVKFARLQV KRNIEREAYF EKSKQARENQ ITMIRKYRVG
ELPDIQIKLQ DIIKPLQLLC QRDSTIGVNV FSSLFTALYK NTPKESIRTF QCNIKKLIDS
IVERCKFNST LVSSILNISE KNLEFSPEFS KIKDISLNSN NHPMAIILCE KLILSLQNTT
KASTTNQAQK LQQQQQLNQG WDSLRELYKS LKEDDIIMGL IEKQMGGDIP YTKKALEFEL
KGDWVNVLKV YDEATSKLES GELNQYQGNL SESETALWEN GRLECFTKLC NWSALKDNFN
SYYPNPNQIF KEKNCDLLLS YFFEFNLKVK ENWNYLYQFI ADLANTKQYQ YLENKFPGEL
AFLEVTRSDH NKASYYVSKF YQAFKHQWSS SHPLAIESRH RILQPLQKIV EVEEFLNLTS
TPIINTLKLD TLLTQWKSRF PTKLDDIMVW DDLIFYRSVL LEKIYERFSS FTSDKSSDEK
VKSTLIQERA ILYHKMSKGA RKLGNIVVSE IYFRQAVKSY PKTKDNDLAF PLVTSLIDIY
CTKARNSPSP IETLDRFVKA LKFIESKKDE ESIINSNENL QKYLMMHGDI FWDIYQLDKK
LGSTLVIDSF KKNSLPINLT SIPINSLKDE LFNSTFKCYS ESIKLHQKST NLLNTTSSSP
SLSISSSSSP YSSTSSSSQP KLSNEILIEK TKTKSAHLKF ANFCDNILKD KISQQTTPTQ
FNEEVIDLAT SVIVSTLEAI KEEIPGSVDK FPRLLEILTQ FEQYSVIARE FKSRVSTIPC
WMFIRWISQM FPYLDLPQGP LILPILLEIA KWYPQAIYFP FKISSEQFGP LAKKISAPLE
KELINPLLDT LVIEFQRLTH PEHRFKDYME EMKSLIKATP KDLNAIAKLN NEIYDDSFNP
STVSGDYNLK FAKEHEASYL SNFGKDSTKL ARMDQKKFLE IFAEMSGNMN KNMKPNSTAS
MKLKDFSGWL ADFDRSNYQT SHQMEIPGQY DGIGKPQPET HVTISSFDTN VLVMGSLRKP
KRVKIHGNDE LDYPFLIKGG EDLRLDQRIQ QLFGIMNEIL KRDTACNKRS LNVTTYQVVP
MTSKVGIIEW LNDTKPLREI LEEQLAHQLK TPRSNVSISK LESTKYHNDW INSFAKYLKP
NSPVGPLYQQ MFIHATRDDC AKKLEKQHSK VPENLLQNGI WSLSSSPESY LFIRNSFARS
LASFSVCSYV IGIGDRHLEN FLISQRDGRL IGIDFGHAFG TATQFLPIPE LMPFRLTRQF
TSFLRPLDSV GLLNHNMTYT LTALQNQKEI LLTTMDVFVK EPLLDWSKLA TRLVKEQGKH
PKDTKNVWFP KQKIQIAKKK LELVNPAYIT LEELSGSVHS GLPYEKALSE IIKGDPKHNI
RAKVNKVCSS VKEQIDCLID QSTDPNILSR AWVGWNGAL
