PRKDC

PRKDC
Subunidad catalítica de la proteína quinasa dependiente de ADN
HUGO 9413
Símbolo PRKDC
Símbolos alt. DNA-PKcs; DNAPK; DNPK1; HYRC; HYRC1; XRCC7; p350
Datos genéticos
Código de gen PRKDC
Tipo de gen Gen codificante
Locus Cr. 8 q11
Estructura/Función proteica
Tamaño 4128 (aminoácidos)
Bases de datos
Número EC 2.7.11.1
Entrez 5591
OMIM 600899
RefSeq NM_006904
UniProt P78527

La subunidad catalítica de la proteína quinasa dependiente de ADN (PRKDC) es una proteína codificada en humanos por el gen PRKDC.

Contenido

Función

PRKDC es la subunidad catalítica de una serina/treonina proteína quinasa no específica nuclear dependiente de ADN denominada DNA-PK. El segundo componente es el antígeno autoinmune Ku. Esta proteína es inactiva y depende de Ku para dirigirse a los extremos del ADN y poner en funcionamiento su actividad quinasa.[1] PRKDC es requerida en el proceso de recombinación no homóloga durante la reparación del ADN, que religa los cortes existentes en las dobles hebras. También es requerida en el proceso de recombinación V(D)J, un proceso que utiliza la recombinación no homóloga para promover la diversidad del sistema inmune. Ratones knockout para el gen PRKDC presentan inmunodeficiencia combinada severa debido al defecto en la recombinación V(D)J.

Se han identificado numerosas proteínas como sustratos para la actividad quinasa de PRKDC. La autofosforilación de PRKDC parece jugar un importante papel en la recombinación no homóloga y se piensa que induce un cambio conformacional que le permite a las enzimas que procesan los extremos, acceder a dichos extremos de los cortes producidos en la doble hebra de ADN.[2] PRKDC también coopera con ATR y ATM para fosforilar proteínas implicadas en el ciclo celular.

Interacciones

La proteína PRKDC ha demostrado ser capaz de interaccionar con:

Véase también

Referencias

  1. ↑ «Entrez Gene: PRKDC protein kinase, DNA-activated, catalytic polypeptide».
  2. ↑ Meek K, Dang V, Lees-Miller SP (2008). «DNA-PK: the means to justify the ends?». Adv. Immunol. 99:  pp. 33–58. doi:10.1016/S0065-2776(08)00602-0. PMID 19117531. 
  3. ↑ Ko, L; Cardona G R, Chin W W (May. 2000). «Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator». Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (11):  pp. 6212–7. ISSN 0027-8424. PMID 10823961. 
  4. ↑ a b c d Kim, S T; Lim D S, Canman C E, Kastan M B (Dec. 1999). «Substrate specificities and identification of putative substrates of ATM kinase family members». J. Biol. Chem. (UNITED STATES) 274 (53):  pp. 37538–43. ISSN 0021-9258. PMID 10608806. 
  5. ↑ a b Goudelock, Dawn Marie; Jiang Kecheng, Pereira Elizabeth, Russell Beatriz, Sanchez Yolanda (Aug. 2003). «Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex». J. Biol. Chem. (United States) 278 (32):  pp. 29940–7. doi:10.1074/jbc.M301765200. ISSN 0021-9258. PMID 12756247. 
  6. ↑ Karmakar, Parimal; Piotrowski Jason, Brosh Robert M, Sommers Joshua A, Miller Susan P Lees, Cheng Wen-Hsing, Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (May. 2002). «Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation». J. Biol. Chem. (United States) 277 (21):  pp. 18291–302. doi:10.1074/jbc.M111523200. ISSN 0021-9258. PMID 11889123. 
  7. ↑ Shao, R G; Cao C X, Zhang H, Kohn K W, Wold M S, Pommier Y (Mar. 1999). «Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes». EMBO J. (ENGLAND) 18 (5):  pp. 1397–406. doi:10.1093/emboj/18.5.1397. ISSN 0261-4189. PMID 10064605. 
  8. ↑ a b Ting, N S; Kao P N, Chan D W, Lintott L G, Lees-Miller S P (Jan. 1998). «DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45». J. Biol. Chem. (UNITED STATES) 273 (4):  pp. 2136–45. ISSN 0021-9258. PMID 9442054. 
  9. ↑ Ma, Yunmei; Pannicke Ulrich, Schwarz Klaus, Lieber Michael R (Mar. 2002). «Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination». Cell (United States) 108 (6):  pp. 781–94. ISSN 0092-8674. PMID 11955432. 
  10. ↑ Suzuki, K; Kodama S, Watanabe M (Sep. 1999). «Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation». J. Biol. Chem. (UNITED STATES) 274 (36):  pp. 25571–5. ISSN 0021-9258. PMID 10464290. 
  11. ↑ Jin, S; Kharbanda S, Mayer B, Kufe D, Weaver D T (Oct. 1997). «Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit». J. Biol. Chem. (UNITED STATES) 272 (40):  pp. 24763–6. ISSN 0021-9258. PMID 9312071. 
  12. ↑ Matheos, Diamanto; Ruiz Marcia T, Price Gerald B, Zannis-Hadjopoulos Maria (Oct. 2002). «Ku antigen, an origin-specific binding protein that associates with replication proteins, is required for mammalian DNA replication». Biochim. Biophys. Acta (Netherlands) 1578 (1-3):  pp. 59–72. ISSN 0006-3002. PMID 12393188. 
  13. ↑ Gell, D; Jackson S P (Sep. 1999). «Mapping of protein-protein interactions within the DNA-dependent protein kinase complex». Nucleic Acids Res. (ENGLAND) 27 (17):  pp. 3494–502. PMID 10446239. 
  14. ↑ Ajuh, P; Kuster B, Panov K, Zomerdijk J C, Mann M, Lamond A I (Dec. 2000). «Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry». EMBO J. (ENGLAND) 19 (23):  pp. 6569–81. doi:10.1093/emboj/19.23.6569. ISSN 0261-4189. PMID 11101529. 
  15. ↑ a b Yavuzer, U; Smith G C, Bliss T, Werner D, Jackson S P (Jul. 1998). «DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D». Genes Dev. (UNITED STATES) 12 (14):  pp. 2188–99. ISSN 0890-9369. PMID 9679063. 
  16. ↑ Wu, X; Lieber M R (Oct. 1997). «Interaction between DNA-dependent protein kinase and a novel protein, KIP». Mutat. Res. (NETHERLANDS) 385 (1):  pp. 13–20. ISSN 0027-5107. PMID 9372844. 
  17. ↑ Liu, L; Kwak Y T, Bex F, García-Martínez L F, Li X H, Meek K, Lane W S, Gaynor R B (Jul. 1998). «DNA-dependent protein kinase phosphorylation of IkappaB alpha and IkappaB beta regulates NF-kappaB DNA binding properties». Mol. Cell. Biol. (UNITED STATES) 18 (7):  pp. 4221–34. ISSN 0270-7306. PMID 9632806. 

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