DNA repair protein XRCC4

Details

Name
DNA repair protein XRCC4
Synonyms
  • X-ray repair cross-complementing protein 4
Gene Name
XRCC4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0003147|DNA repair protein XRCC4
MERKISRIHLVSEPSITHFLQVSWEKTLESGFVITLTDGHSAWTGTVSESEISQEADDMA
MEKGKYVGELRKALLSGAGPADVYTFNFSKESCYFFFEKNLKDVSFRLGSFNLEKVENPA
EVIRELICYCLDTIAENQAKNEHLQKENERLLRDWNDVQGRFEKCVSAKEALETDLYKRF
ILVLNEKKTKIRSLHNKLLNAAQEREKDIKQEGETAICSEMTADRDPVYDESTDEESENQ
TDLSGLASAAVSKDDSIISSLDVTDIAPSRKRRQRMQRNLGTEPKMAPQENQLQEKENSR
PDSSLPETSKKEHISAENMSLETLRNSSPEDLFDEI
Number of residues
336
Molecular Weight
38286.315
Theoretical pI
4.63
GO Classification
Functions
protein C-terminus binding
Processes
cellular protein metabolic process / cellular response to lithium ion / DNA ligation involved in DNA repair / DNA recombination / DNA repair / double-strand break repair / double-strand break repair via nonhomologous end joining / establishment of integrated proviral latency / positive regulation of ligase activity / post-translational protein modification / protein sumoylation / response to X-ray / viral process
Components
cell junction / centrosome / cytosol / DNA ligase IV complex / DNA-dependent protein kinase-DNA ligase 4 complex / nonhomologous end joining complex / nucleoplasm / nucleus
General Function
Protein c-terminus binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0011124|DNA repair protein XRCC4 (XRCC4)
ATGGAGAGAAAAATAAGCAGAATCCACCTTGTTTCTGAACCCAGTATAACTCATTTTCTA
CAAGTATCTTGGGAGAAAACACTGGAATCTGGTTTTGTTATTACACTTACTGATGGTCAT
TCAGCATGGACTGGGACAGTTTCTGAATCAGAGATTTCCCAAGAAGCTGATGACATGGCA
ATGGAAAAAGGGAAATATGTTGGTGAACTGAGAAAAGCATTGTTGTCAGGAGCAGGACCA
GCTGATGTATACACGTTTAATTTTTCTAAAGAGTCTTGTTATTTCTTCTTTGAGAAAAAC
CTGAAAGATGTCTCATTCAGACTTGGTTCCTTCAACCTAGAGAAAGTTGAAAACCCAGCT
GAAGTCATTAGAGAACTTATTTGTTATTGCTTGGACACCATTGCAGAAAATCAAGCCAAA
AATGAGCACCTGCAGAAAGAAAATGAAAGGCTTCTGAGAGATTGGAATGATGTTCAAGGA
CGATTTGAAAAATGTGTGAGTGCTAAGGAAGCTTTGGAGACTGATCTTTATAAGCGGTTT
ATTCTGGTGTTGAATGAGAAGAAAACAAAAATCAGAAGTTTGCATAATAAATTATTAAAT
GCAGCTCAAGAACGAGAAAAGGACATCAAACAAGAAGGGGAAACTGCAATCTGTTCTGAA
ATGACTGCTGACCGAGATCCAGTCTATGATGAGAGTACTGATGAGGAAAGTGAAAACCAA
ACTGATCTCTCTGGGTTGGCTTCAGCTGCTGTAAGTAAAGATGATTCCATTATTTCAAGT
CTTGATGTCACTGATATTGCACCAAGTAGAAAAAGGAGACAGCGAATGCAAAGAAATCTT
GGGACAGAACCTAAAATGGCTCCTCAGGAGAATCAGCTTCAAGAAAAGGAAAAGCCTGAT
TCTTCACTACCTGAGACGTCTAAAAAGGAGCACATCTCAGCTGAAAACATGTCTTTAGAA
ACTCTGAGAAACAGCAGCCCAGAAGACCTCTTTGATGAGATTTAA
Chromosome Location
5
Locus
5q13-q14
External Identifiers
ResourceLink
UniProtKB IDQ13426
UniProtKB Entry NameXRCC4_HUMAN
GenBank Protein ID1151115
GenBank Gene IDU40622
GenAtlas IDXRCC4
HGNC IDHGNC:12831
General References
  1. Li Z, Otevrel T, Gao Y, Cheng HL, Seed B, Stamato TD, Taccioli GE, Alt FW: The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. Cell. 1995 Dec 29;83(7):1079-89. [Article]
  2. 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  4. Critchlow SE, Bowater RP, Jackson SP: Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV. Curr Biol. 1997 Aug 1;7(8):588-98. [Article]
  5. Leber R, Wise TW, Mizuta R, Meek K: The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase. J Biol Chem. 1998 Jan 16;273(3):1794-801. [Article]
  6. Lee KJ, Jovanovic M, Udayakumar D, Bladen CL, Dynan WS: Identification of DNA-PKcs phosphorylation sites in XRCC4 and effects of mutations at these sites on DNA end joining in a cell-free system. DNA Repair (Amst). 2004 Mar 4;3(3):267-76. [Article]
  7. Grawunder U, Wilm M, Wu X, Kulesza P, Wilson TE, Mann M, Lieber MR: Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells. Nature. 1997 Jul 31;388(6641):492-5. [Article]
  8. Chen L, Trujillo K, Sung P, Tomkinson AE: Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase. J Biol Chem. 2000 Aug 25;275(34):26196-205. [Article]
  9. Nick McElhinny SA, Snowden CM, McCarville J, Ramsden DA: Ku recruits the XRCC4-ligase IV complex to DNA ends. Mol Cell Biol. 2000 May;20(9):2996-3003. [Article]
  10. Hsu HL, Yannone SM, Chen DJ: Defining interactions between DNA-PK and ligase IV/XRCC4. DNA Repair (Amst). 2002 Mar 28;1(3):225-35. [Article]
  11. Calsou P, Delteil C, Frit P, Drouet J, Salles B: Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment. J Mol Biol. 2003 Feb 7;326(1):93-103. [Article]
  12. Clements PM, Breslin C, Deeks ED, Byrd PJ, Ju L, Bieganowski P, Brenner C, Moreira MC, Taylor AM, Caldecott KW: 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. DNA Repair (Amst). 2004 Nov 2;3(11):1493-502. [Article]
  13. Foster RE, Nnakwe C, Woo L, Frank KM: Monoubiquitination of the nonhomologous end joining protein XRCC4. Biochem Biophys Res Commun. 2006 Mar 3;341(1):175-83. Epub 2006 Jan 6. [Article]
  14. Ahnesorg P, Smith P, Jackson SP: XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell. 2006 Jan 27;124(2):301-13. [Article]
  15. Yurchenko V, Xue Z, Sadofsky MJ: SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair. Mol Cell Biol. 2006 Mar;26(5):1786-94. [Article]
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  17. Iles N, Rulten S, El-Khamisy SF, Caldecott KW: APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks. Mol Cell Biol. 2007 May;27(10):3793-803. Epub 2007 Mar 12. [Article]
  18. Macrae CJ, McCulloch RD, Ylanko J, Durocher D, Koch CA: APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent hyperphosphorylation following ionizing radiation. DNA Repair (Amst). 2008 Feb 1;7(2):292-302. [Article]
  19. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  20. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  21. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
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  25. Craxton A, Somers J, Munnur D, Jukes-Jones R, Cain K, Malewicz M: XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair. Cell Death Differ. 2015 Jun;22(6):890-7. doi: 10.1038/cdd.2015.22. Epub 2015 Mar 13. [Article]
  26. Xing M, Yang M, Huo W, Feng F, Wei L, Jiang W, Ning S, Yan Z, Li W, Wang Q, Hou M, Dong C, Guo R, Gao G, Ji J, Zha S, Lan L, Liang H, Xu D: Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway. Nat Commun. 2015 Feb 11;6:6233. doi: 10.1038/ncomms7233. [Article]
  27. Ochi T, Blackford AN, Coates J, Jhujh S, Mehmood S, Tamura N, Travers J, Wu Q, Draviam VM, Robinson CV, Blundell TL, Jackson SP: DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science. 2015 Jan 9;347(6218):185-8. doi: 10.1126/science.1261971. [Article]
  28. Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L: Crystal structure of an Xrcc4-DNA ligase IV complex. Nat Struct Biol. 2001 Dec;8(12):1015-9. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03963S-(Dimethylarsenic)CysteineexperimentalunknownDetails