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double stranded DNA-dependent protein kinase (DNA-PK)
Function:
- may function as a primary DNA-damage sensor
- in vitro, DNA-PK requires ds DNA ends or other discontinuities in the DNA double helix
- once bound to DNA, DNA-PK can translocate into the body of DNA to access distal targets
- may also be involved in V(D)J recombination as well as DNA double-strand break repair
Structure:
- trimolecular complex consisting of a 350 kD catalytic subunit & a DNA-targeting component, the human autoimmune antigen Ku
Comparative biology:
- SCID mice show deficiencies in p350DNA-PK [2] & a radio-sensitive cell line was found to be deficient in p350DNA-PK [3]
Interactions
molecular events
General
multisubunit protein
serine/threonine kinase
Figures/Diagrams
Figures/diagrams/slides/tables related to double-stranded DNA-dependent protein kinase
Properties
STATE: active state
MOTIF: S/T phosphorylation site
kinase domain
MOTIF: ATP-binding site
NAME: ATP-binding site
SUBUNITS: Ku autoimmune antigen
MOTIF: DNA-binding motif
active site
MOTIF: P-loop
FOR-BINDING-OF: adenosine triphosphate
DNA-dependent protein kinase catalytic subunit
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
HEAT repeat {288-323}
Ser phosphorylation site {S511}
Ser phosphorylation site {S841}
Ser phosphorylation site {S893}
HEAT repeat {1004-1040}
Ser phosphorylation site {S1052}
leucine zipper
SITE: 1503-1538
FOR-BINDING-VIA: leucine zipper
MOTIF: C1D interaction {1503-1538}
tetratricopeptide repeat {1723-1756}
proteolytic site {2020-2021}
Ser phosphorylation site {S2117}
binding site
SITE: 2436-3212
FOR-BINDING-OF: Ca+2 & integrin-binding protein 1
MOTIF: Thr phosphorylation site {T2603}
Thr phosphorylation site {T2609}
Ser phosphorylation site {S2612}
Thr phosphorylation site {T2638}
Thr phosphorylation site {T2647}
Thr phosphorylation site {T2649}
Thr phosphorylation site {T2671}
Ser phosphorylation site {S2672}
Tyr phosphorylation site {Y2743}
FAT domain
NAME: FAT domain
SITE: 2883-3539
MOTIF: Tyr phosphorylation site
binding site
FOR-BINDING-OF: Paxillin
tetratricopeptide repeat {2920-2948}
tetratricopeptide repeat {2949-2982}
Ser phosphorylation site {S3205}
PI3K/PI4K {3747-4015}
Ser phosphorylation site {S4026}
FATC {4096-4128}
STATE: active state
MISC-INFO: RECOGNITION-MOTIF
:SEQUENCE PEE[T*]Q[T*]QDQPMEEEE
:REF " - Kemp BE, Pearson RB.
Protein kinase recognition sequence motifs.
Trends Biochem Sci. 1990 Sep;15(9):342-6. Review.
PMID: 2238044"
References
- Gottlieb TM, Jackson SP.
Protein kinases and DNA damage.
Trends Biochem Sci. 1994 Nov;19(11):500-3. Review.
PMID: 7855895
- Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM,
Carter T, Oettinger MA, Brown JM.
DNA-dependent kinase (p350) as a candidate gene for the
murine SCID defect.
Science. 1995 Feb 24;267(5201):1178-83.
PMID: 7855601
- Lees-Miller SP, Godbout R, Chan DW, Weinfeld M, Day RS 3rd,
Barron GM, Allalunis-Turner J.
Absence of p350 subunit of DNA-activated protein kinase from
a radiosensitive human cell line.
Science. 1995 Feb 24;267(5201):1183-5.
PMID: 7855602
Components
DNA-dependent protein kinase catalytic subunit; DNA-PK catalytic subunit; DNA-PKcs; DNPK1; p460 (PRKDC, HYRC, HYRC1)
lupus Ku autoimmune antigen, ATP-dependent DNA helicase-2, CTC box binding factor (CTCBF) or thyroid-lupus autoantigen (TLAA)