Ku80

Ku80
	; Estructura tridimensional de la proteína Ku80.
Estructuras disponibles
PDB	Buscar ortólogos: PDBe, RCSB Lista de códigos PDB 1jeq
Identificadores
Símbolos	XRCC5 (HGNC: 12833) FLJ39089; KARP-1; KARP1; KU80; KUB2; Ku86; NFIV
Identificadores; externos	OMIM: 194364 ; EBI: XRCC5; GeneCards: Gen XRCC5; UniProt: XRCC5;
Locus	Cr. 2 q35
	Referencias: AmiGO / QuickGO
Ortólogos
Humano	Ratón
7520
P13010	n/a
NP_066964	n/a

Ku80 es una proteína codificada en humanos por el gen XRCC5.[1] Ku80, junto con Ku70, conforman un heterodímero denominado proteína Ku, que se une a los extremos de la doble hebra de ADN que ha sufrido un corte, y es necesaria para el proceso de recombinación no homóloga durante la reparación del ADN. También es necesaria en el proceso de recombinación V(D)J, que logra incrementar la diversidad antigénica en el sistema inmune de mamíferos utilizando el proceso de recombinación no homóloga.

Además de su papel en el proceso de recombinación no homóloga, Ku también es requerida para el mantenimiento del tamaño del telómero y el silenciamiento de genes subteloméricos.[2]

Ku fue identificada originalmente en pacientes con lupus eritematoso sistémico, en los cuales, tras ser sometidos a análisis, se encontraron elevados niveles de auto-anticuerpos contra esta proteína.[1]

Históricamente, Ku80 ha sido referido bajo diversos nombres, tal y como se muestra a continuación:

Lupus Ku autoantigen protein p80.
ATP-dependent DNA helicase 2 subunit 2.
X-ray repair complementing defective repair in Chinese hamster cells 5.
X-ray repair cross-complementing 5 (XRCC5).

Importancia clínica

Diversos estudios han descrito un raro polimorfismo de tipo microsatélite en este gen que ha sido asociado con cáncer en pacientes que sufren radiosensibilidad.[3]

Interacciones

La proteína Ku80 ha demostrado ser capaz de interaccionar con:

NCOA6[4][5]
GCN5L2[6]
Ku70[7][6][8][9][10]
WRN[11][12]
Tirosina quinasa 2[13]
DNA-PKcs[14][15][7]
TERF2IP[16]
Transcriptasa reversa telomérica[17]
POU2F1[18][15]
PCNA[15][19][20]

Véase también

Referencias

«Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)».
Boulton SJ, Jackson SP (marzo de 1998). «Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing». EMBO J. 17 (6): 1819-28. PMC 1170529. PMID 9501103. doi:10.1093/emboj/17.6.1819.
«Entrez Gene: XRCC5 X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining; Ku autoantigen, 80kDa)».
Ko, L; Cardona G R, Chin W W (mayo. de 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): 6212-7. ISSN 0027-8424. PMID 10823961.
Ko, Lan; Chin William W (Mar. de 2003). «Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase». J. Biol. Chem. (United States) 278 (13): 11471-9. ISSN 0021-9258. PMID 12519782. doi:10.1074/jbc.M209723200.
Barlev, N A; Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman J L, Berger S L (Mar. de 1998). «Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex». Mol. Cell. Biol. (UNITED STATES) 18 (3): 1349-58. ISSN 0270-7306. PMID 9488450.
Gell, D; Jackson S P (Sep. de 1999). «Mapping of protein-protein interactions within the DNA-dependent protein kinase complex». Nucleic Acids Res. (ENGLAND) 27 (17): 3494-502. PMID 10446239.
Yang, C R; Yeh S, Leskov K, Odegaard E, Hsu H L, Chang C, Kinsella T J, Chen D J, Boothman D A (mayo. de 1999). «Isolation of Ku70-binding proteins (KUBs)». Nucleic Acids Res. (ENGLAND) 27 (10): 2165-74. ISSN 0305-1048. PMID 10219089.
Singleton, B K; Torres-Arzayus M I, Rottinghaus S T, Taccioli G E, Jeggo P A (mayo. de 1999). «The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit». Mol. Cell. Biol. (UNITED STATES) 19 (5): 3267-77. ISSN 0270-7306. PMID 10207052.
Song, K; Jung D, Jung Y, Lee S G, Lee I (Sep. de 2000). «Interaction of human Ku70 with TRF2». FEBS Lett. (NETHERLANDS) 481 (1): 81-5. ISSN 0014-5793. PMID 10984620.
Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (Aug. de 2002). «Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus». Nucleic Acids Res. (England) 30 (16): 3583-91. PMID 12177300.
Li, B; Comai L (Sep. de 2000). «Functional interaction between Ku and the werner syndrome protein in DNA end processing». J. Biol. Chem. (UNITED STATES) 275 (37): 28349-52. ISSN 0021-9258. PMID 10880505. doi:10.1074/jbc.C000289200.
Adam, L; Bandyopadhyay D; Kumar R (Jan. de 2000). «Interferon-alpha signaling promotes nucleus-to-cytoplasmic redistribution of p95Vav, and formation of a multisubunit complex involving Vav, Ku80, and Tyk2». Biochem. Biophys. Res. Commun. (UNITED STATES) 267 (3): 692-6. ISSN 0006-291X. PMID 10673353. doi:10.1006/bbrc.1999.1978.
Jin, S; Kharbanda S, Mayer B, Kufe D, Weaver D T (Oct. de 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): 24763-6. ISSN 0021-9258. PMID 9312071.
Matheos, Diamanto; Ruiz Marcia T, Price Gerald B, Zannis-Hadjopoulos Maria (Oct. de 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): 59-72. ISSN 0006-3002. PMID 12393188.
O'Connor, Matthew S; Safari Amin, Liu Dan, Qin Jun, Songyang Zhou (Jul. de 2004). «The human Rap1 protein complex and modulation of telomere length». J. Biol. Chem. (United States) 279 (27): 28585-91. ISSN 0021-9258. PMID 15100233. doi:10.1074/jbc.M312913200.
Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W (Dec. de 2002). «Human Ku70/80 associates physically with telomerase through interaction with hTERT». J. Biol. Chem. (United States) 277 (49): 47242-7. ISSN 0021-9258. PMID 12377759. doi:10.1074/jbc.M208542200.
Schild-Poulter, C; Pope L, Giffin W, Kochan J C, Ngsee J K, Traykova-Andonova M, Haché R J (mayo. de 2001). «The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase». J. Biol. Chem. (United States) 276 (20): 16848-56. ISSN 0021-9258. PMID 11279128. doi:10.1074/jbc.M100768200.
Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki (Oct. de 2002). «A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein». J. Biol. Chem. (United States) 277 (43): 40362-7. ISSN 0021-9258. PMID 12171929. doi:10.1074/jbc.M206194200.
Balajee, A S; Geard C R (Mar. de 2001). «Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells». Nucleic Acids Res. (England) 29 (6): 1341-51. PMID 11239001.

Enlaces externos

MeSH: protein, human Ku80 protein, human (en inglés)

Datos: Q18032397

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[entrez-1] «Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)».

[pmid9501103-2] Boulton SJ, Jackson SP (marzo de 1998). «Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing». EMBO J. 17 (6): 1819-28. PMC 1170529. PMID 9501103. doi:10.1093/emboj/17.6.1819.

[entrez(2)-3] «Entrez Gene: XRCC5 X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining; Ku autoantigen, 80kDa)».

[pmid10823961-4] Ko, L; Cardona G R, Chin W W (mayo. de 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): 6212-7. ISSN 0027-8424. PMID 10823961.

[pmid12519782-5] Ko, Lan; Chin William W (Mar. de 2003). «Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase». J. Biol. Chem. (United States) 278 (13): 11471-9. ISSN 0021-9258. PMID 12519782. doi:10.1074/jbc.M209723200.

[pmid9488450-6] Barlev, N A; Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman J L, Berger S L (Mar. de 1998). «Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex». Mol. Cell. Biol. (UNITED STATES) 18 (3): 1349-58. ISSN 0270-7306. PMID 9488450.

[pmid10446239-7] Gell, D; Jackson S P (Sep. de 1999). «Mapping of protein-protein interactions within the DNA-dependent protein kinase complex». Nucleic Acids Res. (ENGLAND) 27 (17): 3494-502. PMID 10446239.

[pmid10219089-8] Yang, C R; Yeh S, Leskov K, Odegaard E, Hsu H L, Chang C, Kinsella T J, Chen D J, Boothman D A (mayo. de 1999). «Isolation of Ku70-binding proteins (KUBs)». Nucleic Acids Res. (ENGLAND) 27 (10): 2165-74. ISSN 0305-1048. PMID 10219089.

[pmid10207052-9] Singleton, B K; Torres-Arzayus M I, Rottinghaus S T, Taccioli G E, Jeggo P A (mayo. de 1999). «The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit». Mol. Cell. Biol. (UNITED STATES) 19 (5): 3267-77. ISSN 0270-7306. PMID 10207052.

[pmid10984620-10] Song, K; Jung D, Jung Y, Lee S G, Lee I (Sep. de 2000). «Interaction of human Ku70 with TRF2». FEBS Lett. (NETHERLANDS) 481 (1): 81-5. ISSN 0014-5793. PMID 10984620.

[pmid12177300-11] Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (Aug. de 2002). «Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus». Nucleic Acids Res. (England) 30 (16): 3583-91. PMID 12177300.

[pmid10880505-12] Li, B; Comai L (Sep. de 2000). «Functional interaction between Ku and the werner syndrome protein in DNA end processing». J. Biol. Chem. (UNITED STATES) 275 (37): 28349-52. ISSN 0021-9258. PMID 10880505. doi:10.1074/jbc.C000289200.

[pmid10673353-13] Adam, L; Bandyopadhyay D; Kumar R (Jan. de 2000). «Interferon-alpha signaling promotes nucleus-to-cytoplasmic redistribution of p95Vav, and formation of a multisubunit complex involving Vav, Ku80, and Tyk2». Biochem. Biophys. Res. Commun. (UNITED STATES) 267 (3): 692-6. ISSN 0006-291X. PMID 10673353. doi:10.1006/bbrc.1999.1978.

[pmid9312071-14] Jin, S; Kharbanda S, Mayer B, Kufe D, Weaver D T (Oct. de 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): 24763-6. ISSN 0021-9258. PMID 9312071.

[pmid12393188-15] Matheos, Diamanto; Ruiz Marcia T, Price Gerald B, Zannis-Hadjopoulos Maria (Oct. de 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): 59-72. ISSN 0006-3002. PMID 12393188.

[pmid15100233-16] O'Connor, Matthew S; Safari Amin, Liu Dan, Qin Jun, Songyang Zhou (Jul. de 2004). «The human Rap1 protein complex and modulation of telomere length». J. Biol. Chem. (United States) 279 (27): 28585-91. ISSN 0021-9258. PMID 15100233. doi:10.1074/jbc.M312913200.

[pmid12377759-17] Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W (Dec. de 2002). «Human Ku70/80 associates physically with telomerase through interaction with hTERT». J. Biol. Chem. (United States) 277 (49): 47242-7. ISSN 0021-9258. PMID 12377759. doi:10.1074/jbc.M208542200.

[pmid11279128-18] Schild-Poulter, C; Pope L, Giffin W, Kochan J C, Ngsee J K, Traykova-Andonova M, Haché R J (mayo. de 2001). «The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase». J. Biol. Chem. (United States) 276 (20): 16848-56. ISSN 0021-9258. PMID 11279128. doi:10.1074/jbc.M100768200.

[pmid12171929-19] Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki (Oct. de 2002). «A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein». J. Biol. Chem. (United States) 277 (43): 40362-7. ISSN 0021-9258. PMID 12171929. doi:10.1074/jbc.M206194200.

[pmid11239001-20] Balajee, A S; Geard C R (Mar. de 2001). «Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells». Nucleic Acids Res. (England) 29 (6): 1341-51. PMID 11239001.