PRKDC_CHICK
ID PRKDC_CHICK Reviewed; 4134 AA.
AC Q8QGX4; P79791; Q9DEI2;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 121.
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};
GN Name=PRKDC; Synonyms=XRCC7;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphocyte;
RX PubMed=11003390; DOI=10.1007/s002510000227;
RA Fujimori A., Araki R., Fukumura R., Ohhata T., Takahashi H., Kawahara A.,
RA Tatsumi K., Abe M.;
RT "Identification of four highly conserved regions in DNA-PKcs.";
RL Immunogenetics 51:965-973(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11839092; DOI=10.1667/0033-7587(2002)157[0298:saoako]2.0.co;2;
RA Fujimori A., Hashimoto H., Araki R., Saito T., Sato S., Kasama Y.,
RA Tsutsumi Y., Mori M., Fukumura R., Ohhata T., Tatsumi K., Abe M.;
RT "Sequence analysis of 193.4 and 83.9 kbp of mouse and chicken genomic DNAs
RT containing the entire Prkdc (DNA-PKcs) gene.";
RL Radiat. Res. 157:298-305(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3796-3968.
RC STRAIN=White leghorn;
RA Wang H., Meury L., Morais R.;
RT "Nucleotide sequence of a putative member of the chicken
RT phosphatidylinositol 3-kinase family.";
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine-protein kinase that acts as a molecular
CC sensor for DNA damage. Involved in DNA nonhomologous end joining (NHEJ)
CC required for double-strand break (DSB) repair and V(D)J recombination.
CC Must be bound to DNA to express its catalytic properties. Promotes
CC processing of hairpin DNA structures in V(D)J recombination by
CC activation of the hairpin endonuclease artemis (DCLRE1C). 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. Act as a scaffold protein to aid
CC the localization of DNA repair proteins to the site of damage. The
CC assembly of the DNA-PK complex at DNA ends is also required for the
CC NHEJ ligation step. Found at the ends of chromosomes, suggesting a
CC further role in the maintenance of telomeric stability and the
CC prevention of chromosomal end fusion. As part of the DNA-PK complex,
CC involved in the early steps of ribosome assembly by promoting the
CC processing of precursor rRNA into mature 18S rRNA in the small-subunit
CC processome (By similarity). Recognizes the substrate consensus sequence
CC [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX, thereby
CC regulating DNA damage response mechanism (By similarity).
CC {ECO:0000250|UniProtKB:P78527, ECO:0000250|UniProtKB:P97313}.
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 -!- SUBUNIT: DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed
CC of XRCC6/Ku70 and XRCC5/Ku86). Component of the core long-range non-
CC 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.
CC {ECO:0000250|UniProtKB:P78527}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P78527}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:P78527}.
CC -!- PTM: Autophosphorylated at two clusters, the T2609 cluster and the
CC S2056 cluster. Autophosphorylated on Ser-2055, Thr-2609, Thr-2638 and
CC Thr-2647. Ser-2055 and Thr-2609 are DNA damage-inducible
CC phosphorylation sites (inducible with ionizing radiation, IR)
CC dephosphorylated by PPP5C (By similarity). Autophosphorylation induces
CC a conformational change that leads to remodeling of the DNA-PK complex,
CC requisite for efficient end processing and DNA repair (By similarity).
CC Autophosphorylation in trans within DNA-PK complexes loaded on DNA ends
CC leads to the dissociation of PRKDC from DNA and the transition into the
CC short-range NHEJ complex (By similarity). Autophosphorylation of the
CC T2609 cluster is required for hematopoietic development and protein
CC synthesis in erythrocytes precursors (By similarity).
CC {ECO:0000250|UniProtKB:P78527, ECO:0000250|UniProtKB:P97313}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
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DR EMBL; AB016240; BAA36956.1; -; mRNA.
DR EMBL; AB028136; BAB91148.1; -; Genomic_DNA.
DR EMBL; U83109; AAB41106.1; -; mRNA.
DR RefSeq; NP_989989.2; NM_204658.2.
DR SMR; Q8QGX4; -.
DR STRING; 9031.ENSGALP00000021030; -.
DR PaxDb; Q8QGX4; -.
DR PRIDE; Q8QGX4; -.
DR GeneID; 395376; -.
DR KEGG; gga:395376; -.
DR CTD; 5591; -.
DR VEuPathDB; HostDB:geneid_395376; -.
DR eggNOG; KOG0891; Eukaryota.
DR InParanoid; Q8QGX4; -.
DR OrthoDB; 26975at2759; -.
DR PhylomeDB; Q8QGX4; -.
DR Reactome; R-GGA-351433; ATM mediated phosphorylation of repair proteins.
DR Reactome; R-GGA-353423; Non-homologous end joining (NHEJ).
DR PRO; PR:Q8QGX4; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0070419; C:nonhomologous end joining complex; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; TAS:Reactome.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IEA:InterPro.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IBA:GO_Central.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0042254; P:ribosome biogenesis; IEA:UniProtKB-KW.
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; 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 2: Evidence at transcript level;
KW ATP-binding; DNA damage; DNA repair; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ribosome biogenesis;
KW Serine/threonine-protein kinase; TPR repeat; Transferase.
FT CHAIN 1..4134
FT /note="DNA-dependent protein kinase catalytic subunit"
FT /id="PRO_0000225633"
FT REPEAT 900..937
FT /note="HEAT 1"
FT REPEAT 1000..1036
FT /note="HEAT 2"
FT REPEAT 1050..1085
FT /note="HEAT 3"
FT REPEAT 1265..1305
FT /note="TPR 1"
FT REPEAT 1722..1755
FT /note="TPR 2"
FT REPEAT 2207..2240
FT /note="TPR 3"
FT DOMAIN 2880..3545
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 3728..4059
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 4102..4134
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 2611..2631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3734..3740
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 3925..3933
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 3945..3970
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 2055
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2609
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2612
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2638
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2647
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT CONFLICT 3796..3804
FT /note="TYQVIPMTT -> VHISEYFCS (in Ref. 3; AAB41106)"
FT /evidence="ECO:0000305"
FT CONFLICT 3965..3968
FT /note="MPFR -> DALP (in Ref. 3; AAB41106)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 4134 AA; 472657 MW; 8907B1EA6E7E9AA8 CRC64;
MAGGVQECLQ ELHGCLQPGD AMRGYGLLRG LGEACLTCLA GGALALHVSL VFAPERGLLA
FVCRSLGVEE FRECREEALK FLCVFLERIG ERAHPYACSL KQTCISVYTK ERAAKCKIPA
LELLIKLLQS LRRSCLMEEM KVGEIFNKFY GELAVRSKIS DTVLEKIYEL LGVLGEVHPA
DMINNSEKLF RAYLGELKTQ MTSATRVPKL PIVAGCLRGL TALMYNFTKS VDEDAQTSKE
IFDFAVKAIR PQVDQKRYAV HLAGLQLFSW HAAQFGTLLL DSYVMLFETM CRWCGHTNQE
LKKAGHNALD SFLKQMSLMV AKDAELHKSK LKFFMEQFYG IIRRMDSSNK ELSIAIRGYG
LFAAPCKAMH PADVDAMYIE LLQRCKQMYL TEAETIDDHL YQLPSFLQSI ASVIFHLDTI
PEVYTPVLEH LVVLQINSFP RYSEKMQLVC CRSIIKVFLA LSIKGPVLWN FISTVVHQGL
IRVFSKPMKF SKDVFGKETS GSEEFPESGE VDTARWKVPT YKDYLYLFRS LLSCDTMKES
IFEEENFLTG NSPLQSLNRL LYDELIKSIL KIIEKLDLTV QKLNVHEQDE NETDSAFIGP
TSDPASNLQP KKPTDFIAFI NLVEFCRDIL PDKHVEYFQP WVYSFGYELI IHSTRLPLIS
GFYKLLSVTM KIAKKIKYFE GVGPKSLRKA TEDPEKSSCF ALFAKFGKEV TAKMKQYKDE
LLASCLNFLL SLPHDIVMLD IKAYIPALQN AFKLGLSCTP MADLGLDALE DWSAHIPRHI
MQPYYKDVLP LLDGYLKNSA TTVEPQNNWE VRKLSRAAQK GFNKIVIQRL RKAKTSSLDD
NPSLEAVRTR VARLLGSLGG QINHNLITAT SAEEMMKKCV SWDTKNHLSF AVPFADMKPV
IYLDVFLPRV TDLALSASDR QTKIAACELL HSIVAYMLGK ASQMPERQQG PPPMHQLYKR
IFPVLLRLAC DVDQVTRQLY EPLVMQLIHW FTNNKKFESQ DTVTFLEAIL SGIVDPVDST
LRDFCGQCVR EFLKWSIKQT TPKQQEKSPA NTKSLFKRLY SLALHPSAFK RLGAALAFNS
IYREFREENS LVEQFVFEAL VVFLESLALT HTDEKSLGTT QQCCDAINHL KRIIKHKAPA
LNKEGKRRVP RGFPATKSVC LQDVVMWLLV QCGRPQTECR HKAMELFYEF VPLLPGNNSP
SSWLADVLKK RDVSFLINKF EGGGSDAKSP SGILSQPTLR DMQEPFSLLT VMRWMDMFLA
ALDCYNTFFE LRMIKPHEIL GVNERSSFLE AVDFFLETIA LHDIHAAEQC FDCRSRGNIF
SPQEREVYNY SKCTIIVRIM EFVTMILEIC QQDFWKLLEK ELLNANFIEL LVMTVCDPSH
IGFNTADVQV MKNLPDISVR LLKALMKSPY KEYLQLCLKK RITPQSFEDL CSVDLFNSDA
RFDQVRFSAV LSACKQLQKS GLLHSVLHSQ DERPHPSIGS KLLSVVYKSI APGSERSSLP
AVDISSKRLA DRLLQLAFAI DDQCEELVSL LLNTVVLSVP LSKASERNFV DFSHGQYFYS
LFSDTINQQL LKNLDVIVIH LMESSVSNPQ MVGSILNGML DQSFRERTIR KQQGVKLVTA
VLRNWKRLDS WWAKDSSPES KMAVLTLLAK VLQIDSSVSF NTSHEAFTAV FDTYTSLLTD
QNLGLNLKGH AVIILPFFTN LSGEKLHDLK NALDQLVAFN FPMSSDEFPK GTLKHNNYVD
CTKKFLDALE LSQSPMLLQL MTEVLCRDHR HSMEDLFQAS FKRISRRSST DKQVVLLDTV
HKMFQNEDLL SNIVRQAFVD RSLLTLMSHC SLDALREFFC KIIVQAMDTL NSRFTKSNEC
VFDTQITKKM GYYKMLEVMY IRLSKDDVHS KDSKINQAYR GSVSVEGNEL TKALIKLCYD
AFTENMAGEN QLLEKRRQYH CAAYNCAIAV ISCVFTESKF YQGFLFTEKS EKNLLIFENL
IDLKRQYVFP VEIEVPLERK KRYIAIRKEA REAWNDGQDE PKYLASASYM MDSSLSEEMS
QFDFSTGVQG FSYSSQDVTA SSAHFRRKET SEYMVLNDEM ELEMDELNQH ECMAPLTTLI
KHMQRNQITP KVEEGVIPVD LPLWMKFLHS KLGNPSVPLN IRLFIAKLIV NTEDVFRPYA
KQWLGPMLQL VVSGDNGGEG IHYMVVEIAV TVLSWTSVTT PKGNIKDEIL ANRLLEFLMK
NAFHQKRAVF RHNLEIIKTV IECWKNCLSI PYSLIFEKFS SGDPDTKDNS VGIQLLGIVL
ANNLPPFDLK CEIDRVRYFQ ALVSNMGLLR YKEVYAAAAE VLGLALQYIA ERQNILEDPV
YDCVIKQLKR HQNTQQDKFI ICLNKVVKNF PPLADRFMNA VFFLIPKLHG VMKNYCLEVI
MCRAEEIPDL YLQLKSKDFI QIMKHRDDER QRVCLDIIYK MLSTLKPPEL KELLPGVTGF
ISHPSVICRQ RMYDILMWIY DNYSDPESQA DGDSQEVLSL AKEILLQGLI DENAELQLIV
RNFWSDETRL PANILDRMLM LLNSLYSAKI ETQYLSLITN FLLEMTSKSP DYSRKIFEHP
LSECKFHDFV IDSSWRYRST MLTPMFVETQ ASQSTNRNSS QERSLSISGS VGGRVRATQR
QYEFTPTQNV SGRSSFNWLT GNSIDTLAEY TVPSSSESLS SSMLLVNKRS EKFKQAAFKP
VGPDFGKKRL SLPGDKVDSK TKGIDERAEI LRLRRRFLKD QEKVSLIYAR KGVAEQKREK
EMKSELKMKF DGQVTLYRSY RVGDLPDIQI EHCSLIAPLQ GLAQKDPTFA KQLFSSLFGG
IFCEVKKSKI PSEKKAIIQK LLKDFNHFLS TSVSYFPPFI ACIQEISYKH RELLELDSAN
VSTSCLASLQ QPVGILLLEH ALMALSPAEE PPSKRMRGRT ELPPDVVKWL ELAKLYRSLG
DYDVLRGIFS GKIGTKDITQ QALLAEARSD YAEAAKCYDE ALSKEDWEDG EPTEAEKDFW
ELASLECYDH LTEWKSLEYC ATVNIDSGKP PDLNKTWSDP FYQETYLPYI IRSKLKLLLN
GENDQTLLTF IDEAMKTEQK KALIEMHYSQ ELSLLYILQD DFDRAKYYIG NGIQIFMQSY
SSIDTLLYQS RMSKLQSVQA LTEIQDFINF MTKTSNIASQ AKSLKRLLRT WTSRYPDAKM
DPMNIWDDII TNRCFFLDKL QEKFLCDKAN DSMEVDEESS VGDQMEVDQQ DEDIHSMIRS
CKFNMKLKMI ESARKQNSFS IAKKLLKGLR REAKTREDWL VRWNYAYCRF VHSCSQSQSC
PERVLSVLKT ISLLEDTKSD YLNKNIMAFR NQNLLLGTTY HIMANALSQD PKCCEQIEEE
KTGKILELSG ESSESPEKIL AGLNKRAFQC FSSAARKSEE EVQSLSMEHV DVKGVIDAYM
TLVGFCDQHL RKEEEGSLEI NAADLQLFPA IVVEKMIKAL KLNSREARLR FPRLLQIIER
YPAETLGLVT RELPSVPCWQ FIGWISQMMA LLDKDEAVAV QHTVEEIVDT YPQAIIYPFT
ISSESYCFKD TAAGCRNKEF VASIKNKLDR GGVVQDFIHA LEQLSNPVML FKDWVADVRN
ELVKTQRNKI ILKEMYEGMY KNLGDVKAPG LGWLRKRFVQ AFGKDFDSHF GKGGSKLLDM
KISDFNEITT ALLTKMNKTH KEPGNLKECS PWMSEFRAEF LRNELEVPGQ YDGKGKPLPE
YHVKISGFDE RIMVLESLRK PKRITIRGSD EQEHPFLVKG GEDLRQDQRI EQLFDVMNIV
LSRDAACSQR NMQLKTYQVI PMTTRLGLIK WLENTCTLKE FLRNSMTEEE DANYNSLKGP
RAAYSDWLSK MGGKAQGLSR YNAMYKNASR TETVIAFKSR ESSVPEDLLR RAFVKMSTSP
EAFLALRSHF VSSHALMCVS HWILGIGDRH LSNFMINKET GGMVGIDFGH AFGSATQFLP
VPELMPFRLT RQFVNLMMPV KEWGLIYSVM VHALRAYRAD PDLLISTMDV FVKEPSLDWK
NFEQRQLKKG GTWIKEINTA EVNWYPLQKV SYVKRKLTGA NPARITCDEL RLGYEKLPFY
NDFAAVARGS ADHNIRAKEP EDRLSEETQV RCLIDQATDP NLLGRVWEGW EPWM
