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Protein FULL name: DNA repair protein XRCC4, X-ray repair cross-complementing protein 4.,
XRCC4 (Homo sapiens) is product of expression of
XRCC4
gene.
XRCC4 is involved in:
NHEJ in Homo sapiens
FUNCTION: Involved in DNA non-homologous end joining (NHEJ)
required for double-strand break repair and V(D)J recombination.
Binds to DNA and to DNA ligase IV (LIG4). The LIG4-XRCC4 complex
is responsible for the NHEJ ligation step, and XRCC4 enhances the
joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA
ends is dependent on the assembly of the DNA-dependent protein
kinase complex DNA-PK to these DNA ends.
SUBUNIT: Homodimer and homotetramer in solution. The homodimer
associates with LIG4, and the LIG4-XRCC4 complex associates in a
DNA-dependent manner with the DNA-PK complex formed by the Ku
p70/p86 dimer (G22P1/G22P2) and PRKDC. Seems to interact directly
with PRKDC but not with the Ku p70/86 dimer. Interacts with
XLF/Cernunnos. Interacts with APTX and APLF.
INTERACTION:
O00499:BIN1; NbExp=3; IntAct=EBI-717592, EBI-719094;
Q9H9Q4:NHEJ1; NbExp=3; IntAct=EBI-717592, EBI-847807;
Q96T60:PNKP; NbExp=1; IntAct=EBI-717592, EBI-1045072;
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Widely expressed.
PTM: Phosphorylated by PRKDC. The phosphorylation seems not to be
necessary for binding to DNA. Phosphorylation by CK2 promotes
interaction with APTX.
PTM: Monoubiquitinated.
PTM: Sumoylation at Lys-210 is required for nuclear localization
and recombination efficiency. Has no effect on ubiquitination.
SIMILARITY: Belongs to the XRCC4 family.
WEB RESOURCE: Name=NIEHS-SNPs;
[LINK]
Links to other databases:
Protein sequence:
MERKISRIHLVSEPSITHFLQVSWEKTLESGFVITLTDGHSAWTGTVSES
EISQEADDMAMEKGKYVGELRKALLSGAGPADVYTFNFSKESCYFFFEKN
LKDVSFRLGSFNLEKVENPAEVIRELICYCLDTIAENQAKNEHLQKENER
LLRDWNDVQGRFEKCVSAKEALETDLYKRFILVLNEKKTKIRSLHNKLLN
AAQEREKDIKQEGETAICSEMTADRDPVYDESTDEESENQTDLSGLASAA
VSKDDSIISSLDVTDIAPSRKRRQRMQRNLGTEPKMAPQENQLQEKENSR
PDSSLPETSKKEHISAENMSLETLRNSSPEDLFDEI
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XRCC4 (Homo sapiens) is able to recognize following damages:
XRCC4 (Homo sapiens) belongs to following protein families:
References:
Title
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Authors
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Journal
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The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination.
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Li Z, Otevrel T, Gao Y, Cheng HL, Seed B, Stamato TD, Taccioli GE, Alt FW
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Cell
Dec. 1, 1995
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Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells.
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Grawunder U, Wilm M, Wu X, Kulesza P, Wilson TE, Mann M, Lieber MR
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Nature
July 31, 1997
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Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV.
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Critchlow SE, Bowater RP, Jackson SP
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Curr Biol
Aug. 1, 1997
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The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase.
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Leber R, Wise TW, Mizuta R, Meek K
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J Biol Chem
Feb. 16, 1998
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Ku recruits the XRCC4-ligase IV complex to DNA ends.
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Nick McElhinny SA, Snowden CM, McCarville J, Ramsden DA
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Mol Cell Biol
May 1, 2000
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Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase.
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Chen L, Trujillo K, Sung P, Tomkinson AE
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J Biol Chem
Aug. 25, 2000
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Crystal structure of an Xrcc4-DNA ligase IV complex.
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Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L
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Nat Struct Biol
Dec. 1, 2001
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Defining interactions between DNA-PK and ligase IV/XRCC4.
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Hsu HL, Yannone SM, Chen DJ
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DNA Repair (Amst)
March 28, 2002
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Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment.
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Calsou P, Delteil C, Frit P, Drouet J, Salles B
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J Mol Biol
Jan. 7, 2003
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Tetramerization and DNA ligase IV interaction of the DNA double-strand break repair protein XRCC4 are mutually exclusive.
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Modesti M, Junop MS, Ghirlando R, van de Rakt M, Gellert M, Yang W, Kanaar R
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J Mol Biol
Nov. 21, 2003
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Complete sequencing and characterization of 21,243 full-length human cDNAs.
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Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S
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Nat Genet
Feb. 1, 2004
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Identification of DNA-PKcs phosphorylation sites in XRCC4 and effects of mutations at these sites on DNA end joining in a cell-free system.
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Lee KJ, Jovanovic M, Udayakumar D, Bladen CL, Dynan WS
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DNA Repair (Amst)
March 4, 2004
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The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
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Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J
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Genome Res
Oct. 1, 2004
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The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.
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Clements PM, Breslin C, Deeks ED, Byrd PJ, Ju L, Bieganowski P, Brenner C, Moreira MC, Taylor AM, Caldecott KW
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DNA Repair (Amst)
Nov. 2, 2004
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XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining.
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Ahnesorg P, Smith P, Jackson SP
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Cell
Feb. 27, 2006
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SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair.
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Yurchenko V, Xue Z, Sadofsky MJ
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Mol Cell Biol
March 1, 2006
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Monoubiquitination of the nonhomologous end joining protein XRCC4.
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Foster RE, Nnakwe C, Woo L, Frank KM
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Biochem Biophys Res Commun
March 3, 2006
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A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses.
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Kanno S, Kuzuoka H, Sasao S, Hong Z, Lan L, Nakajima S, Yasui A
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EMBO J
April 18, 2007
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APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks.
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Iles N, Rulten S, El-Khamisy SF, Caldecott KW
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Mol Cell Biol
May 1, 2007
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APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent hyperphosphorylation following ionizing radiation.
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Macrae CJ, McCulloch RD, Ylanko J, Durocher D, Koch CA
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DNA Repair (Amst)
Jan. 1, 2008
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A quantitative atlas of mitotic phosphorylation.
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Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP
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Proc Natl Acad Sci U S A
Aug. 5, 2008
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Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
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Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK
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Sci Signal
Jan. 1, 2009
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Last modification of this entry: Oct. 6, 2010.
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